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Search Results (1,428)

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10 pages, 1177 KiB  
Article
Impact of Sex on Infection Risk in Patients with Systemic Lupus Erythematosus
by R. Borrelli, S. Nicola, F. Corradi, I. Badiu, L. Lo Sardo, N. Rashidy, A. Quinternetto, M. Mazzola, F. Meli, E. Saracco, I. Vitali, S. Negrini and L. Brussino
Bioengineering 2025, 12(1), 59; https://doi.org/10.3390/bioengineering12010059 - 13 Jan 2025
Viewed by 170
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that exhibits considerable diversity in terms of both clinical and immunological manifestations. Since its female-to-male ratio is around 9:1, it is well recognized that systemic lupus erythematosus mostly affects women, especially those of [...] Read more.
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that exhibits considerable diversity in terms of both clinical and immunological manifestations. Since its female-to-male ratio is around 9:1, it is well recognized that systemic lupus erythematosus mostly affects women, especially those of childbearing age. There is a greater susceptibility to infections in adult patients with systemic lupus erythematosus (SLE) compared to the general population. However, only a small number of studies have attempted to analyze this risk using real-life data, and even fewer have successfully assessed the influence of sex. Materials and Methods: A retrospective study was conducted, enrolling patients and dividing them into two groups based on their biological sex. Infectious episodes were identified from medical records and categorized by severity. Patients were stratified according to disease duration and treatment received. Logistic regression analysis was used to calculate the odds ratio (OR), with a 95% confidence interval (CI) for the assessment of risk factors. Multivariable logistic regression was performed to adjust for potential confounders. Model fit was evaluated using the Hosmer–Lemeshow test, and interactions between variables were tested. Sensitivity analyses were conducted to assess the robustness of the findings. Results: A total of 119 patients (107 females and 12 males) were included in the analysis. No significant difference in age was found between sexes (t = −0.715, p = 0.487), but disease duration was significantly shorter in males (t = 3.35, p = 0.003). Logistic regression showed a significant association between male sex and infection risk (β = 0.9426, p = 0.05), with males having an almost sixfold higher probability of infection compared to females (OR 5.675, 95% CI: 1.4479–22.2477, p = 0.0127). Disease duration (β = 0.0250, p = 0.102) and smoking status (β = 0.4529, p = 0.078) were not statistically significant. Lastly, correlation analysis revealed a significant association between SS-A antibodies and infection rate (r = 0.291, p = 0.003). Conclusions: This study highlights a significant sex-based disparity in the risk of infections among SLE patients, with males being at a higher risk compared to females. The differences in the distribution of infections, such as the higher prevalence of pneumonia in males and urinary tract infections in females, suggest that sex-specific factors, including immunological and hormonal differences, may influence infection susceptibility. Our findings emphasize the need for tailored clinical management, with increased vigilance for infections in male patients, to improve prevention strategies and targeted therapeutic interventions in this subgroup. Full article
(This article belongs to the Special Issue Engineering Cells for Immunotherapy)
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<p>Distribution of infectious events (IEs) in males.</p>
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<p>Distribution of infectious events (IEs) in females.</p>
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<p>Distribution of infections for sex. URTI: upper respiratory tract infection, UTI: urinary tract infection, CTI: connective tissue infection, HZV: herpes zoster virus, SARS-CoV-2: severe acute respiratory syndrome coronavirus 2, APN: acute pyelonephritis, EBV: Epstein–Barr virus, GI: gastrointestinal.</p>
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15 pages, 276 KiB  
Review
Food Is Medicine: Diet Assessment Tools in Adult Inflammatory Bowel Disease Research
by Vibeke Andersen, Anette Liljensøe, Laura Gregersen, Behrooz Darbani, Thorhallur Ingi Halldorsson and Berit Lilienthal Heitmann
Nutrients 2025, 17(2), 245; https://doi.org/10.3390/nu17020245 - 10 Jan 2025
Viewed by 475
Abstract
Background: Diet significantly impacts the onset and progression of inflammatory bowel disease (IBD), and diet offers unique opportunities for treatment and preventative purposes. However, despite growing interest, no diet has been conclusively associated with improved long-term clinical and endoscopic outcomes in IBD, and [...] Read more.
Background: Diet significantly impacts the onset and progression of inflammatory bowel disease (IBD), and diet offers unique opportunities for treatment and preventative purposes. However, despite growing interest, no diet has been conclusively associated with improved long-term clinical and endoscopic outcomes in IBD, and evidence-based dietary guidelines for IBD remain scarce. This narrative review critically examines dietary assessment methods tailored to the unique needs of IBD, highlighting opportunities for precision and inclusivity. Methods: We conducted a comprehensive literature review using search terms related to diet, diet assessment, nutrition, food, sex, gender, equity, and IBD. Results: The identified dietary assessment tools evaluated nutritional quality, dietary patterns, food processing, lifestyle interactions, inflammatory potential, and effects of specific nutrients. Advanced methods, including biomarkers, multi-omics approaches, and digital tools, were highlighted as being complementary to traditional approaches, offering enhanced precision and real-time monitoring. Women remain under-represented in dietary research but face unique nutritional needs due to hormonal cycles, pregnancy, and higher malnutrition risks in IBD. Discussion: Traditional diet assessment methods remain valuable but are often limited by misreporting biases. Advanced approaches may provide greater precision, enabling real-time monitoring and personalised dietary tracking. Incorporating considerations of sex, gender, age, ethnicity, socioeconomic, and sustainability enhances the relevance and applicability of these methods. Addressing these multifaceted aspects of dietary assessment in IBD can facilitate robust interventional trials. Conclusions: Diet assessment tools are essential for developing personalised dietary interventions in IBD, informing evidence-based guidelines, and improving health outcomes and quality of life in IBD. Full article
21 pages, 15458 KiB  
Review
Sex Determination in Reptiles: A Review
by Alessandro Vetere, Michele Capasso and Francesco Di Ianni
Animals 2025, 15(2), 168; https://doi.org/10.3390/ani15020168 - 10 Jan 2025
Viewed by 280
Abstract
Reptile biodiversity is rapidly declining, with over 11,733 recognized species across 1226 genera being documented, many of which are endangered. Captive breeding programs play a crucial role in conservation; however, effective management requires accurate sex determination, especially due to the fact that many [...] Read more.
Reptile biodiversity is rapidly declining, with over 11,733 recognized species across 1226 genera being documented, many of which are endangered. Captive breeding programs play a crucial role in conservation; however, effective management requires accurate sex determination, especially due to the fact that many reptile species exhibit minimal or no sexual dimorphism. When present, sexual dimorphism manifests as differences such as size, coloration, and morphological features influenced by evolutionary pressures and hormones. Various sex determination techniques are employed due to the lack of external sexual characteristics in many species. These methods include probing, hydrostatic eversion, popping, ultrasound, CT, radiography, contrast radiography, endoscopy, and genotypic sex determination. Accurate sex determination is crucial for the success of captive breeding programs and the conservation of reptile species. Advanced imaging and molecular methods offer promising non-invasive alternatives but may not be universally accessible or effective. An understanding of the unique reproductive anatomy and the use of appropriate sexing techniques are fundamental to establishing breeding groups, preventing aggressive behaviours among groups, and ensuring the long-term survival of endangered reptile populations. Full article
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<p>(<b>A</b>) Adult female Hermann’s tortoise (<span class="html-italic">Testudo hermanni</span>), ventral view. The tail is noticeably smaller (yellow arrows) compared to that of the male (<b>B</b>), yellow arrows. The angle formed by the right and left anal scutes is wider in the male (<b>B</b>, white arrows) than in the female (<b>A</b>, white arrows).</p>
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<p>(<b>A</b>) An adult, mature male bearded dragon (<span class="html-italic">Pogona vitticeps</span>), positioned in dorsal recumbency. The presence of well-developed femoral pores is evident (black arrows). (<b>B</b>) An adult, mature female bearded dragon (<span class="html-italic">Pogona vitticeps</span>), positioned in dorsal recumbency. Femoral pores are less developed (black arrows).</p>
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<p>(<b>A</b>) subadult male veiled chameleons (<span class="html-italic">Chamaeleo calyptratus</span>). A tarsal spur is evident on the lateral aspect of the tarsus (yellow arrow). (<b>B</b>) Adult female of the same species. The tarsal spur is absent.</p>
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<p>Close-up of the right lateral region dorsal to the cloaca in two specimens of the common boa (<span class="html-italic">Boa constrictor</span>). (<b>A</b>) Adult male specimen: the dashed circle highlights a well-developed femoral spur. (<b>B</b>) Adult female specimen: the spur is not evident.</p>
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<p>(<b>A1</b>) Probing procedure in a male albino California kingsnake (<span class="html-italic">Lampropeltis getula californiae</span>). The probe is gently inserted into the hemipenile pocket until resistance to further advancement is encountered. (<b>A2</b>) The depth of probe insertion is measured by counting the postcloacal scales. In this case, the probe advanced into the pocket to a depth of five postcloacal scales. This counting method serves as a comparative tool in cases of ambiguous results between different specimens. (<b>B1</b>) Probing procedure in a female California kingsnake (<span class="html-italic">Lampropeltis getula californiae</span>). Note that in females, the probe advances only to the length of two postcloacal scales (<b>B2</b>), compared to males, due to the absence of hemipenes and the reduced length of the hemipenile pockets.</p>
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<p>(<b>A</b>) Ultrasonographic view showing the right testis (18.14 × 19.63 mm) in a mature male Greek tortoise (<span class="html-italic">Testudo graeca</span>) during the breeding season (June). (<b>B</b>) Ultrasonographic view showing the right ovary in a mature female Greek tortoise (<span class="html-italic">Testudo graeca</span>) after the breeding season (September). Multiple round, hyperechoic, 7 mm diameter early vitellogenic follicles are visible. The ultrasonographic views were obtained from the right prefemoral fossa.</p>
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<p>CT scans of a female common musk turtle (<span class="html-italic">Sternotherus odoratus</span>) affected by preovulatory stasis. (<b>A</b>) Transverse plane, (<b>B</b>) coronal plane, and (<b>C</b>) sagittal plane, showing numerous altered follicles filling the caudal coelom, with (hypodense areas yellow arrows) alternating with hyperdense areas of the yolk.</p>
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<p>On the left (<b>A</b>), radiograph of a mature male black-headed monitor (<span class="html-italic">Varanus tristis</span>), showing evident mineralized hemibacula (yellow arrows). On the right (<b>B</b>), a mature female of the same species; hemibacula are absent. Courtesy of Dr. Clément Paillusseau.</p>
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<p>(<b>A</b>) Coeloscopic image of an immature testis in an immature male Indian star tortoise (<span class="html-italic">Geochelone elegans</span>). The testis appears as a smooth, pink to orange, elongated structure. (<b>B</b>) Coeloscopic image of an immature ovary in an immature female Indian star tortoise (<span class="html-italic">Geochelone elegans</span>). The ovary appears as a yellowish, elongated structure composed of small clusters of clear, fluid-filled follicles.</p>
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<p>Cystoscopic appearance of gonads in Indonesian blue-tongued skink (<span class="html-italic">Tiliqua gigas</span>). (<b>A</b>) Ovary of a subadult, sexually immature specimen. Black arrows indicate blood vessels associated with the bladder, while white arrows indicate ovarian vessels. (<b>B</b>) Ovary of a sexually immature specimen weighing only 28 g. Several ivory-colored follicles of equal size are visible (asterisk). Laterally to the adrenal gland (Ad), the oviduct can be observed as a flattened, whitish structure running parallel to the ovary. (<b>C</b>) Testis of a sexually mature adult specimen. Black arrows indicate blood vessels associated with the bladder, while white arrows indicate testicular vessels. (<b>D</b>) Testis of an immature specimen weighing 26 g. A pale red, immature testis is marked by an asterisk. Ad: adrenal gland.</p>
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<p>Cloacoscopic appearance of the urodeum in an adult female blue tongue skink (<span class="html-italic">Tiliqua gigas</span>). Four papillae are visible dorsally at the level of the urodeum. The two cranial papillae represent the outlets of the oviducts (white arrows), while the two caudal papillae (black arrows) correspond to the openings of the ureters. Do: dorsal.</p>
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28 pages, 686 KiB  
Review
The Impact of Sulforaphane on Sex-Specific Conditions and Hormone Balance: A Comprehensive Review
by Jed W. Fahey and Mirran Raphaely
Appl. Sci. 2025, 15(2), 522; https://doi.org/10.3390/app15020522 - 8 Jan 2025
Viewed by 442
Abstract
The health-promoting, preventive, protective, and therapeutic applications of the natural compound sulforaphane (SF) produced from its biogenic precursor in broccoli, glucoraphanin, are extremely well established. SF has been the subject of thousands of studies and over 125 clinical trials. The many mechanisms of [...] Read more.
The health-promoting, preventive, protective, and therapeutic applications of the natural compound sulforaphane (SF) produced from its biogenic precursor in broccoli, glucoraphanin, are extremely well established. SF has been the subject of thousands of studies and over 125 clinical trials. The many mechanisms of action of SF in mammalian systems have been extensively documented. SF is the most potent naturally occurring inducer of the Keap1/Nrf2 pathway, which is most well-known for its upregulation of antioxidant and detoxification mechanisms and activation of pathways resulting in the inhibition of inflammation. Much of this regulation involves the various hormonal axes of the body. However, the influence of SF on hormone-mediated health conditions remains unexplored in recent scholarly reviews. This review aims to address this gap by exploring many of these interactions, with a focus on the health and wellness issues specific to both females and males. Full article
(This article belongs to the Special Issue Functional Food: From Discovery to Application)
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Graphical abstract
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<p>The many mechanisms (not colored) of action of sulforaphane and some of the the diseases or conditions in which effects of sulforaphane have been examined experimentally (orange); magenta shading for emphasis of mode of action most targeted by clinical studies. (adapted from [<a href="#B1-applsci-15-00522" class="html-bibr">1</a>]).</p>
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14 pages, 2325 KiB  
Article
Natural Enemies Acquire More Prey Aphids from Hormone-Treated Insect-Attracting Plants
by Xiaosheng Jiang, Xingrui Zhang, Guodong Han, Shovon Chandra Sarkar and Feng Ge
Plants 2025, 14(2), 147; https://doi.org/10.3390/plants14020147 - 7 Jan 2025
Viewed by 531
Abstract
Exogenous plant hormones regulate the agronomic and physiological performance of plants and thus can influence the abundance of insect groups. We surveyed the arthropods on flowering plants Cnidium monnieri and found that the abundance of natural enemies Propylaea japonica and Orius minutus in [...] Read more.
Exogenous plant hormones regulate the agronomic and physiological performance of plants and thus can influence the abundance of insect groups. We surveyed the arthropods on flowering plants Cnidium monnieri and found that the abundance of natural enemies Propylaea japonica and Orius minutus in the plots treated with salicylic acid (SA) and indole acetic acid (IAA) was significantly increased compared with those in the clean water (control) plots. Then, we investigated the effects of spraying SA, IAA, and clean water on the population parameters of Semiaphis heraclei reared on C. monnieri. Our results from the age-stage, two-sex life table analysis revealed a significantly shorter pre-adult duration for aphids reared on SA-treated C. monnieri compared to those reared on the other two treatments. The intrinsic rate of increase, finite rate of increase, and net reproductive rate of aphids reared on SA- and IAA-treated C. monnieri were significantly higher than those of aphids reared on clean water-treated C. monnieri. The fecundity rate was higher under the SA and IAA treatments than in the control, but the difference was not significant. This improved the ability of flowering plants to attract natural enemies by providing a larger food source. Full article
(This article belongs to the Special Issue Functional Plants for Ecological Control of Agricultural Pests)
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<p>Response of aphid populations to different treatments. (<b>A</b>) Population dynamics of aphids <span class="html-italic">Semiaphis heraclei</span> on 5 flowering plants of <span class="html-italic">Cnidium monnieri</span>, which were treated with salicylic acid; (<b>B</b>) Population dynamics of <span class="html-italic">Semiaphis heraclei</span> on 5 flowering plants of <span class="html-italic">Cnidium monnieri</span>, which were treated with indoleacetic acid; (<b>C</b>) Total cumulative number of <span class="html-italic">Semiaphis heraclei</span> during all the sampling periods (5 times) according to the visual observations of the salicylic acid-treated <span class="html-italic">Cnidium monnieri</span>; (<b>D</b>) Total cumulative number of <span class="html-italic">Semiaphis heraclei</span> during all the sampling periods (5 times) according to the visual observations of the indoleacetic acid-treated <span class="html-italic">Cnidium monnieri</span> (due to the climate conditions in 2022, the number of aphids on the entire plot was very low that year, so data from 2022 were not included). * means <span class="html-italic">p</span> ≤ 0.05; ** means <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>Population dynamics of natural enemies on flowering plants treated with water 150 mg/L, salicylic acid, and 150 mg/L indoleacetic acid in 2021 and 2022. (<b>A</b>): Population dynamics of <span class="html-italic">Orius minutus</span> on one square meter of <span class="html-italic">Cnidium monnieri</span> in 2021; (<b>B</b>): Population dynamics of <span class="html-italic">Propylaea japonica</span> on one square meter of <span class="html-italic">Cnidium monnieri</span> n 2021; (<b>C</b>): Population dynamics of <span class="html-italic">Orius minutus</span> on one square meter of <span class="html-italic">Cnidium monnieri</span> n 2022; (<b>D</b>): Population dynamics of <span class="html-italic">Propylaea japonica</span> on one square meter of <span class="html-italic">Cnidium monnieri</span> in 2022.</p>
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<p>Age-specific survival curves (Sxj) of <span class="html-italic">Semiaphis heraclei</span> treated with salicylic acid and indoleacetic acid.</p>
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<p>Age-specific survival rate (lx), age-specific reproduction rate (mx), age-specific reproduction rate (fx), and age-specific reproduction value (lxmx) in parthenogenetic populations of <span class="html-italic">Semiaphis heraclei</span> treated with salicylic acid and indoleacetic acid.</p>
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<p>Age-specific life expectation of <span class="html-italic">Semiaphis heraclei</span> treated with salicylic acid and indoleacetic acid exj.</p>
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<p>Age-specific reproductive rate values of <span class="html-italic">Semiaphis heraclei</span> treated with salicylic acid and indoleacetic acid (vxj).</p>
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22 pages, 4818 KiB  
Article
A Comparative Transcriptome Analysis Reveals the Effects of Letrozole and 17α-Methyltestosterone on the Expression of Reproductive-Related Genes in Golden Pompano (Trachinotus ovatus)
by Qi Zhou, Yan Wang, Yuwen Guo, Guangli Li, Tao Wang and Huapu Chen
Fishes 2025, 10(1), 21; https://doi.org/10.3390/fishes10010021 - 6 Jan 2025
Viewed by 297
Abstract
Aromatase inhibitor letrozole (LZ) and 17α-methyltestosterone (MT) are commonly used for sex control breeding to induce female-to-male sex reversal in aquaculture. However, studies on the molecular regulatory mechanisms of LZ and MT are still limited. Here, a comparative transcriptome analysis was conducted on [...] Read more.
Aromatase inhibitor letrozole (LZ) and 17α-methyltestosterone (MT) are commonly used for sex control breeding to induce female-to-male sex reversal in aquaculture. However, studies on the molecular regulatory mechanisms of LZ and MT are still limited. Here, a comparative transcriptome analysis was conducted on the hypothalamus, the gonad, and the liver of golden pompano (Trachinotus ovatus) after 30 days of LZ and MT treatment, which demonstrated significant sexual size dimorphism. Following LZ treatment, the transcriptome data identified 156, 890, and 1286 different expression genes (DEGs) in the hypothalamus, the liver, and the gonad, respectively. After MT treatment, the transcriptome data identified 114, 876, and 950 DEGs in the hypothalamus, the liver, and the gonad, respectively. Functional enrichment analysis revealed that DEGs were involved in oocyte meiosis and steroid-hormone synthesis following LZ treatment. Similarly, the analysis indicated that DEGs were associated with cysteine and methionine metabolism and steroid-hormone synthesis after MT treatment. Further analysis showed that LZ treatment can promote the first meiotic division but inhibit the second meiotic division of the oocyte. MT treatment promotes polyamine synthesis to induce oocyte apoptosis, both of which affect the trajectory of ovarian differentiation in golden pompano. However, LZ and MT have converse effects in sex hormone synthesis. LZ inhibits estrogen metabolism but promotes cholesterol synthesis by regulating sqle, cyp3a40, ugt1a1, and ugt2a1, while MT promotes estrogen metabolism but inhibits the conversion of cholesterol to pregnenolone by regulating cyp19a1, cyp1a, and hsd17b7. This study reveals that both LZ and MT may inhibit the ovarian differentiation and induce masculinization through different regulatory mechanisms, which provides a fundamental insight into the sex control breeding in aquaculture. Full article
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<p>The detailed procedure for the treatment of golden pompano by LZ or MT.</p>
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<p>Analysis of gene expression patterns in hypothalamus tissues of the golden pompano. (<b>A</b>) Number of DEGs. (<b>B</b>) Venn diagrams showing the distribution of DEGs under the influence of LZ and MT. (<b>C</b>,<b>D</b>) Heatmap indicates the expression levels of all DEGs in the Hy-A and the Hy-B groups throughout processing periods.</p>
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<p>Analysis of gene expression patterns in gonad tissues of the golden pompano. (<b>A</b>) Number of DEGs. (<b>B</b>) Venn diagrams showing the distribution of DEGs under the influence of LZ and MT. (<b>C</b>,<b>D</b>) Heatmap indicates the expression levels of all DEGs in the Hy-A and the Hy-B groups throughout processing periods.</p>
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<p>Analysis of gene expression patterns in liver tissues of the golden pompano. (<b>A</b>) Number of DEGs. (<b>B</b>) Venn diagrams showing the distribution of DEGs under the influence of LZ and MT. (<b>C</b>,<b>D</b>) Heatmap indicates the expression levels of all DEGs in the Hy-A and the Hy-B groups throughout processing periods.</p>
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<p>Volcano plots of gene expression differences. Red dots: up-regulation; blue dots: down-regulation; grey dots: normal-regulation. (<b>A</b>) Hypothalamus tissue transcriptome (LZ); (<b>B</b>) hypothalamus tissue transcriptome (MT); (<b>C</b>) ovarian tissue transcriptome (LZ); (<b>D</b>) ovarian tissue transcriptome (MT); (<b>E</b>) liver tissue transcriptome (LZ); (<b>F</b>) liver tissue transcriptome (MT).</p>
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<p>Functional annotation of DEGs based on GO classification. The horizontal axis indicates GO function and the vertical axis indicates the number of genes with GO function. (<b>A</b>) Pathway enrichment analysis of DEGs in the hypothalamus under the influence of LZ; (<b>B</b>) pathway enrichment analysis of DEGs in the hypothalamus under the influence of MT; (<b>C</b>) pathway enrichment analysis of DEGs in the gonad under the influence of LZ; (<b>D</b>) pathway enrichment analysis of DEGs in the gonad under the influence of MT; (<b>E</b>) pathway enrichment analysis of DEGs in the liver under the influence of LZ; (<b>F</b>) pathway enrichment analysis of DEGs in the liver under the influence of MT.</p>
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<p>DEGs are significantly enriched in KEGG pathways. (<b>A</b>) LZ affects the pathway enrichment analysis of DEGs in the hypothalamus. (<b>B</b>) Pathway enrichment analysis of DEGs in the MT-influenced hypothalamus. (<b>C</b>) Pathway enrichment analysis of DEGs in the LZ-influenced hypothalamus. (<b>D</b>) Pathway enrichment analysis of DEGs in the gonad under the influence of MT. (<b>E</b>) Pathway enrichment analysis of DEGs in the liver under the influence of LZ. (<b>F</b>) Pathway enrichment analysis of DEGs in the liver under the influence of MT. Pathways and enrichment factors are indicated on the vertical and horizontal axes, respectively. The size of the dots indicates the number of genes and the color indicates the q-value.</p>
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<p>(<b>A</b>) The expression profiles of 8 hypothalamus genes using qRT-PCR (LZ); (<b>B</b>) the expression profiles of 8 hypothalamus genes using qRT-PCR (MT); (<b>C</b>) the expression profiles of 10 ovarian genes using qRT-PCR (LZ); (<b>D</b>) the expression profiles of 9 ovarian genes using qRT-PCR (MT); (<b>E</b>) validation of the expression profiles of 9 liver genes using qRT-PCR (LZ); (<b>F</b>) validation of the expression profiles of 10 liver genes using qRT-PCR (MT).</p>
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<p>Reproduction-related DEGs under the influence of LZ.</p>
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<p>Reproduction-related DEGs under the influence of MT.</p>
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22 pages, 2217 KiB  
Review
Sex and Region-Specific Differences in Microglial Morphology and Function Across Development
by Indra R. Bishnoi and Evan A. Bordt
Neuroglia 2025, 6(1), 2; https://doi.org/10.3390/neuroglia6010002 - 4 Jan 2025
Viewed by 303
Abstract
Microglia are exceptionally dynamic resident innate immune cells within the central nervous system, existing on a continuum of morphologies and functions throughout their lifespan. They play vital roles in response to injuries and infections, clearing cellular debris, and maintaining neural homeostasis throughout development. [...] Read more.
Microglia are exceptionally dynamic resident innate immune cells within the central nervous system, existing on a continuum of morphologies and functions throughout their lifespan. They play vital roles in response to injuries and infections, clearing cellular debris, and maintaining neural homeostasis throughout development. Emerging research suggests that microglia are strongly influenced by biological factors, including sex, developmental stage, and their local environment. This review synthesizes findings on sex differences in microglial morphology and function in key brain regions, including the frontal cortex, hippocampus, amygdala, hypothalamus, basal ganglia, and cerebellum, across the lifespan. Where available, we examine how gonadal hormones influence these microglial characteristics. Additionally, we highlight the limitations of relying solely on morphology to infer function and underscore the need for comprehensive, multimodal approaches to guide future research. Ultimately, this review aims to advance the dialogue on these spatiotemporally heterogeneous cells and their implications for sex differences in brain function and vulnerability to neurological and psychiatric disorders. Full article
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<p>Gonadal hormone secretion across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in mice and rats. In the late embryonic and early neonatal period, testosterone and its aromatized metabolite estradiol drive the defeminization and masculinization of males. In females, the relative absence of early gonadal hormone secretion allows for feminization. A second surge of gonadal hormones occurs during adolescence. Around P40, testosterone increases in males, and estradiol and progesterone increase in females, oscillating with the estrous cycle before declining in late adulthood. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/w25p782" target="_blank">https://BioRender.com/w25p782</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the frontal cortex of mice and rats. All effects are in comparison to opposite-sex conspecifics. While we are starting to uncover sex differences in microglial morphology during the juvenile and adolescent periods [<a href="#B56-neuroglia-06-00002" class="html-bibr">56</a>], during adulthood, females may exhibit more ramified microglia that may prioritize anti-inflammatory or homeostatic functions [<a href="#B55-neuroglia-06-00002" class="html-bibr">55</a>,<a href="#B66-neuroglia-06-00002" class="html-bibr">66</a>]. In contrast, microglial characteristics in adult male rodents may show a bias for heightened immune reactivity in the frontal cortex [<a href="#B55-neuroglia-06-00002" class="html-bibr">55</a>,<a href="#B66-neuroglia-06-00002" class="html-bibr">66</a>]. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/r88b180" target="_blank">https://BioRender.com/r88b180</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the hippocampus of mice and rats. All effects are in comparison to opposite-sex conspecifics. During the neonatal period, the microglia of female rodents may be more phagocytic [<a href="#B78-neuroglia-06-00002" class="html-bibr">78</a>,<a href="#B79-neuroglia-06-00002" class="html-bibr">79</a>]. Microglia of females may transition into a more ramified state from adolescence to adulthood, while microglia of male rodents may take on a more phagocytic role within the hippocampus [<a href="#B55-neuroglia-06-00002" class="html-bibr">55</a>,<a href="#B78-neuroglia-06-00002" class="html-bibr">78</a>]. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/m04r955" target="_blank">https://BioRender.com/m04r955</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the amygdala of mice and rats. All effects are in comparison to opposite-sex conspecifics. While the morphology and function of microglia during the neonatal period are more inconsistent, amygdalar microglia in females may prioritize an earlier transition toward a ramified state [<a href="#B39-neuroglia-06-00002" class="html-bibr">39</a>,<a href="#B78-neuroglia-06-00002" class="html-bibr">78</a>], which continues into adolescence and adulthood, while microglia in the male amygdala may retain more phagocytic roles [<a href="#B55-neuroglia-06-00002" class="html-bibr">55</a>,<a href="#B78-neuroglia-06-00002" class="html-bibr">78</a>]. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/o82o967" target="_blank">https://BioRender.com/o82o967</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the hypothalamus of mice and rats. All effects are in comparison to opposite-sex conspecifics. Transient sex differences have been observed during the neonatal period [<a href="#B40-neuroglia-06-00002" class="html-bibr">40</a>,<a href="#B78-neuroglia-06-00002" class="html-bibr">78</a>], but research on the other developmental stages is particularly lacking. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/t84z394" target="_blank">https://BioRender.com/t84z394</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the basal ganglia of mice and rats. All effects are in comparison to opposite-sex conspecifics. Many studies on region-specific effects of microglia within the basal ganglia do not statistically evaluate sex differences. When sex differences are evaluated, morphological variations are observed in adulthood [<a href="#B108-neuroglia-06-00002" class="html-bibr">108</a>]. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/w81x526" target="_blank">https://BioRender.com/w81x526</a> (accessed on 3 December 2024).</p>
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<p>Sex differences in microglial characteristics across the embryonic (embryonic day 0 to birth), neonatal (postnatal day 0 to 10), juvenile (postnatal day 11 to 20), adolescent (postnatal day 21 to 59), and adulthood (postnatal day 60 onwards) developmental stages in the cerebellum of mice and rats. All effects are in comparison to opposite-sex conspecifics. While some studies report sex differences during the neonatal period [<a href="#B81-neuroglia-06-00002" class="html-bibr">81</a>], other measures suggest a lack of sex-dependent variations. In adulthood, microglia in males may play more phagocytic roles [<a href="#B112-neuroglia-06-00002" class="html-bibr">112</a>]. Created in BioRender. Bishnoi, I. (2024) <a href="https://BioRender.com/q92y700" target="_blank">https://BioRender.com/q92y700</a> (accessed on 3 December 2024).</p>
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28 pages, 4740 KiB  
Article
Elucidation of Factors Affecting the Age-Dependent Cancer Occurrence Rates
by Jun Xiao, Yangkun Cao, Xuan Li, Long Xu, Zhihang Wang, Zhenyu Huang, Xuechen Mu, Yinwei Qu and Ying Xu
Int. J. Mol. Sci. 2025, 26(1), 275; https://doi.org/10.3390/ijms26010275 - 31 Dec 2024
Viewed by 286
Abstract
Cancer occurrence rates exhibit diverse age-related patterns, and understanding them may shed new and important light on the drivers of cancer evolution. This study systematically analyzes the age-dependent occurrence rates of 23 carcinoma types, focusing on their age-dependent distribution patterns, the determinants of [...] Read more.
Cancer occurrence rates exhibit diverse age-related patterns, and understanding them may shed new and important light on the drivers of cancer evolution. This study systematically analyzes the age-dependent occurrence rates of 23 carcinoma types, focusing on their age-dependent distribution patterns, the determinants of peak occurrence ages, and the significant difference between the two genders. According to the SEER reports, these cancer types have two types of age-dependent occurrence rate (ADOR) distributions, with most having a unimodal distribution and a few having a bimodal distribution. Our modeling analyses have revealed that (1) the first type can be naturally and simply explained using two age-dependent parameters: the total number of stem cell divisions in an organ from birth to the current age and the availability levels of bloodborne growth factors specifically needed by the cancer (sub)type, and (2) for the second type, the first peak is due to viral infection, while the second peak can be explained as in (1) for each cancer type. Further analyses indicate that (i) the iron level in an organ makes the difference between the male and female cancer occurrence rates, and (ii) the levels of sex hormones are the key determinants in the onset age of multiple cancer types. This analysis deepens our understanding of the dynamics of cancer evolution shared by diverse cancer types and provides new insights that are useful for cancer prevention and therapeutic strategies, thereby addressing critical gaps in the current paradigm of oncological research. Full article
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<p>The landscape of age-dependent occurrence rates of different cancers. (<b>A</b>,<b>B</b>) Fitting for occurrence rate distributions having unimodality (<b>A</b>) and bimodality (<b>B</b>) with 95% confidence intervals being depicted by the red lines. (<b>C</b>) The peak ages of cancer occurrence rate distributions across different cancer types. (<b>D</b>) Comparison between cancer ADOR distributions of female and male patients of ESCA and THCA. (<b>E</b>) Fold changes in cancer occurrence rates in male vs. female.</p>
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<p>Regression models of age-dependent (x-axis) cancer occurrence rates against cancer risk and the availability levels of growth signals needed by each cancer type. (<b>A</b>–<b>C</b>) The regression models for (<b>A</b>) ESCA, (<b>B</b>) TGCT, and (<b>C</b>) THCA, respectively. The red line represents the cancer occurrence rate; the orange line is the predicted occurrence rate based on cancer risk level (black line), and the other lines are for the concentrations of circulatory growth signals. The symbol * represents the interaction term, indicating the product of cancer risk and the concentration of circulatory growth signals.</p>
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<p>Co-expression patterns of cell cycle genes. (<b>A</b>) Circos plot illustrating the co-expression patterns of cell cycle genes in seven cancer types. The outermost circle lists cancer types, followed by a middle circle representing co-expression clusters of cell cycle genes, and an inner circle with a heatmap detailing gene correlations (row and column orders are identical). At the center, the bar plot shows the gene numbers for each co-expression clusters. The colors for cancer types are consistent with those used in other panels of this figure. (<b>B</b>) The Sankey diagram showing the predicted growth signals and their receptors for regression model of ADOR in the seven cancer types. (<b>C</b>) Combination chart presenting regression analysis for PC1 of each co-expressed cluster against growth signal-related receptors, genes involved in de novo deoxyribonucleotides synthesis, and PC1 of other cell cycle cluster(s). The top bar chart shows adjusted R<sup>2</sup> values, with color indicating <span class="html-italic">p</span>-values. The lower bubble chart depicts the contribution of each factor to the regression model, with color coding for <span class="html-italic">p</span>-values. (<b>D</b>) Violin plots showing the R<sup>2</sup> values for random forest-based regressions with 10-fold cross-validation (CV). (<b>E</b>) Bar plots for the R<sup>2</sup> values for random forest-based regressions in both the training and test sets using the independent datasets.</p>
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<p>Viral infection rates related to cancer occurrence rate. (<b>A</b>,<b>B</b>) Regression models of HBV (<b>A</b>) and HCV (<b>B</b>) infection rates in liver cancer. (<b>C</b>) Liver cancer occurrence rates with HBV infection, with HCV infection, and without viral infection. (<b>D</b>) The regression model for age-dependent HCV infection rate in the USA population. (<b>E</b>) The regression model for cancer occurrence rates of patients with HCV infection against cancer risk and viral infection rate in the USA population. (<b>F</b>) Differences in age-dependent occurrence rates of liver cancer between female and male. (<b>G</b>,<b>H</b>) Examination of gender differences in age-dependent viral infection rates in the U.S. population for HBV (<b>G</b>) and HCV (<b>H</b>). (<b>I</b>) The HBV and HCV infection rates in liver cancer patients by gender. (<b>J</b>) HCV infection rate among population, categorized by gender and shown across different NHANES datasets. (<b>K</b>) Cervical cancer occurrence rates with HPV 16/18 infection and those without such infection. The symbol * represents the interaction term, indicating the product of cancer risk and the concentration of circulatory growth signals.</p>
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<p>Gender- and organ-specific disparity in cancer occurrence rates. (<b>A</b>) Enriched pathways among upregulated genes in males vs. females across different organs, focused on pathways enriched in at least three organ types. (<b>B</b>) Correlation between immune responses and iron levels in colon cancer, illustrating a significant association. (<b>C</b>) Box plots for variations in ferritin levels between genders across different age groups, measured using the Wilcoxon test for statistical significance. Significance levels are indicated as ‘ns’ for not significant, ‘***’ for <span class="html-italic">p</span>-value ≤ 0.001, and ‘****’ for <span class="html-italic">p</span>-value ≤ 0.0001. (<b>D</b>) Levels of blood ferritin levels across different cancer types, where 100,000 random reassignments of cancer and non-cancer labels among samples. (<b>E</b>) Scatter plots comparing the actual cancer incidence ratio (male vs. female) in different ages with those predicted by the expression difference of iron-related genes for COAD. The blue dots represent the actual (x-axis) and predicted (y-axis) ratios for specific ages, with the red line showing a linear regression, indicating strong agreement between the values. (<b>F</b>) Enriched pathways among upregulated genes in female thyroid tissues, highlighting the most enriched pathways in different databases. (<b>G</b>) Scatter plots showing the regression analysis for cancer incidence ratio (male vs. female) against fold change of <span class="html-italic">E2</span> (male vs. female) in THCA. Each blue dot represents a specific age point, with the red line indicating the linear regression, demonstrating that the estradiol ratio effectively explains the incidence ratio in THCA.</p>
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<p>Cancers with early (age &lt; 75) vs. late (≥75) peak ages. (<b>A</b>) Cancer types arranged in the increasing peak age with early ones colored in brown and late ones in blue. (<b>B</b>) Gene set enrichment analysis (GSEA) results in cancers with early peak ages vs. those in cancers with late peak ages. (<b>C</b>) Sex hormones identified to be cell cycle driving across different cancers. (<b>D</b>) Pathway enrichment analysis among genes that show a negative correlation with <span class="html-italic">AR</span> expression in TGCT. (<b>E</b>) Heatmap displaying the differential expression of enzyme genes involved in androgen biosynthesis between normal tissues and cancerous tissues. (<b>F</b>) Correlations between <span class="html-italic">HSD17B3</span> expression and intracellular pH reduction signals in normal testicular tissue.</p>
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23 pages, 2147 KiB  
Article
Bariatric Surgery as a Molecular Modulator: The Role of FSHR Polymorphisms in Enhancing eNOS Expression and Reproductive Hormone Dynamics in Women with Severe Obesity
by Charalampos Voros, Despoina Mavrogianni, Kyriakos Bananis, Alexios Karakasis, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Raphail Mantzioros, Panagiota Kondili, Menelaos Darlas, Regina Sotiropoulou, Diamantis Athanasiou, Dimitris Mathiopoulos, Panagiotis Antsaklis, Dimitrios Loutradis and Georgios Daskalakis
Biomedicines 2025, 13(1), 67; https://doi.org/10.3390/biomedicines13010067 - 30 Dec 2024
Viewed by 366
Abstract
Background/Objectives: Severe obesity (BMI > 40 kg/m2) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism [...] Read more.
Background/Objectives: Severe obesity (BMI > 40 kg/m2) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism groups in women with extreme obesity. Methods: Twenty-nine women with extreme obesity had bariatric surgery. Pre- and post-surgery levels of eNOS and reproductive hormones such as follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and antral follicle count (AFC) were assessed. Patients were divided into three FSHR polymorphism groups (Ser/Ser, Asn/Asn, and Ser/Asn), and results were compared between them. Statistical techniques were used to determine changes and relationships. Results: Bariatric surgery led to substantial increases in eNOS expression across all FSHR polymorphism groups (p < 0.0001), with the Ser/Ser group exhibiting the most variability. Prior to surgery, the Ser/Ser group had substantially higher FSH levels (7.41 ± 0.60 mIU/mL) than the Asn/Asn group (5.20 ± 0.63 mIU/mL, p < 0.001). Following surgery, FSH levels rose in the Ser/Ser group (9.45 ± 0.87 mIU/mL), with significant differences between the Ser/Ser and Ser/Asn groups (mean difference = 0.97, p = 0.019). SHBG levels had a negative connection with eNOS expression after surgery (r = −0.365, p = 0.049). AMH and AFC remained constant throughout polymorphism groups. BMI decreased uniformly, with an average of 15.2 ± 1.8 kg six months after surgery. Conclusions: Bariatric surgery improves vascular health and regulates reproductive hormones, especially in individuals with the Ser/Ser genotype. These findings indicate the possibility of combining genetic testing and bariatric therapies to improve infertility treatment in obese women. Full article
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<p>Flow chart for patient exclusion and inclusion in the research.</p>
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<p>Depicts the distribution of FSH levels in the three FSHR polymorphism groups (Asn/Asn, Asn/Ser, and Ser/Ser) prior to surgery. The Ser/Ser group has the highest median FSH levels and the broadest range when compared to the other two groups. In contrast, the Asn/Asn and Asn/Ser groups exhibit lower FSH levels, with the Asn/Asn group showing the least fluctuation. These visual findings are consistent with the statistical analysis, demonstrating significant variations in FSH levels for the Ser/Ser group, possibly indicating a larger impact of this polymorphism on FSH regulation.</p>
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<p>Comparison of eNOS Expression Across FSHR Polymorphism Groups Prior Surgery.</p>
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<p>FSH Levels Across FSHR Polymorphism Groups after Surgery.</p>
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<p>LH Levels Across FSHR Polymorphism Groups after Surgery.</p>
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<p>eNOS Expression Across FSHR Polymorphism Groups after Surgery.</p>
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<p>Comparison of eNOS Expression Across Polymorphism Groups Pre- and Post-Surgery.</p>
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11 pages, 1166 KiB  
Article
A Retrospective Study in Trans Individuals Undergoing Gender Affirming Testosterone Treatment: Can Changes in Prolactin Counteract the Negative Effects on the Lipid Profile?
by Jojo Steininger, Katalin Widmann, Ulrike Kaufmann, Marlene Hager, Rodrig Marculescu, Robert Krysiak and Johannes Ott
Biomedicines 2025, 13(1), 66; https://doi.org/10.3390/biomedicines13010066 - 30 Dec 2024
Viewed by 326
Abstract
Background/Objectives: Gender-affirming hormone therapy (GAHT) is known to influence the lipid profiles of trans men and transmasculine individuals. Recent data show that moderate prolactin (PRL) elevations might exert beneficial metabolic effects (“HomeoFIT-PRL model”). The aim of this study is to investigate changes in [...] Read more.
Background/Objectives: Gender-affirming hormone therapy (GAHT) is known to influence the lipid profiles of trans men and transmasculine individuals. Recent data show that moderate prolactin (PRL) elevations might exert beneficial metabolic effects (“HomeoFIT-PRL model”). The aim of this study is to investigate changes in PRL levels and possible associations between PRL and lipid profiles in this population after a year of GAHT. Methods: In a retrospective cohort study, 97 participants, who received GAHT with testosterone, were included. Blood lipids, PRL, and sex steroid hormone levels were evaluated prior to and at 10–14 months after treatment started. Results: The difference in PRL levels between baseline and follow-up was significant (p = 0.007) with a median difference of +2.3 ng/mL. Concerning blood lipids, the decline in high-density lipoprotein cholesterol (HDL-C) reached statistical significance (median 56 mg/dL versus 50 mg/dL; p < 0.001), and low-density lipoprotein cholesterol (LDL-C) and triglyceride levels increased (p = 0.023 and p = 0.045, respectively). Individuals with a PRL > 25 ng/mL at follow-up (n = 20, 20.6%) revealed increases in total cholesterol and LDL-C significantly less often. Overall, participants frequently displayed unfavorable changes in their lipid profile after 10–14 months of GAHT, as well as a slight but significant increase in PRL. About 20% of patients showed mild-to-moderate hyperprolactinemia (PRL > 25 ng/mL). However, such changes were associated with potentially beneficial dynamics in the lipid profile, at least for triglycerides. Conclusions: These findings seem in line with the HomeoFIT-PRL model suggesting that moderate elevations in PRL levels might exert beneficial metabolic effects. Increases in PRL after testosterone were common. Full article
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<p>PRISMA flow chart of patient identification, screening, and inclusion.</p>
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<p>Differences in PRL and lipid levels between baseline and follow-up examinations: correlation analyses. (<b>A</b>) correlation between difference in total colesterole and prolactin (PRL), (<b>B</b>) correlation between difference in HDL-C and PRL, (<b>C</b>) correlation between difference in LDL-C and PRL, (<b>D</b>) correlation between difference in triglycerides and PRL.</p>
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<p>ROC analysis for the optimized cut-off for follow-up PRL levels. Patients were subdivided into those who revealed a stable course or a decline in total cholesterol (<b>A</b>) and triglyceride (<b>B</b>) levels and those who experienced an increase at follow-up.</p>
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23 pages, 310 KiB  
Review
Endocrine Hormones and Their Impact on Pubertal Gynecomastia
by Zi’ang Shi and Minqiang Xin
J. Clin. Med. 2025, 14(1), 158; https://doi.org/10.3390/jcm14010158 - 30 Dec 2024
Viewed by 401
Abstract
Pubertal gynecomastia (PG) is a common condition characterized by the abnormal development and hyperplasia of unilateral or bilateral breast tissue in adolescent males, affecting up to 50% of appropriately aged adolescents and exhibiting rising prevalence over recent years. The etiology of PG is [...] Read more.
Pubertal gynecomastia (PG) is a common condition characterized by the abnormal development and hyperplasia of unilateral or bilateral breast tissue in adolescent males, affecting up to 50% of appropriately aged adolescents and exhibiting rising prevalence over recent years. The etiology of PG is multifaceted, encompassing physiological, pharmacological, and pathological factors. This narrative review synthesizes evidence from a comprehensive selection of peer-reviewed literature, including observational studies, clinical trials, systematic reviews, and case reports, to explore the pivotal role of endocrine hormones in the pathogenesis of PG. Specifically, it examines the effects of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), progesterone (P), prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), thyroid hormones (T3, T4), parathyroid hormone (PTH), anti-Müllerian hormone (AMH), human chorionic gonadotropin (hCG), and leptin. By synthesizing current insights, this review underscores the intricate hormonal dynamics underlying PG and their implications for diagnosis and treatment. Conclusively, the findings advocate for a personalized approach in the clinical management of PG, with particular emphasis on the hormonal milieu as a cornerstone of therapeutic strategy. Full article
(This article belongs to the Section Endocrinology & Metabolism)
13 pages, 1381 KiB  
Review
Laryngeal Cancer in Women: Unveiling Gender-Specific Risk Factors, Treatment Challenges, and Survival Disparities
by Barbara Verro, Simona Fiumara, Giuseppe Saraniti and Carmelo Saraniti
Curr. Oncol. 2025, 32(1), 19; https://doi.org/10.3390/curroncol32010019 - 29 Dec 2024
Viewed by 547
Abstract
Laryngeal cancer is one of the main causes of morbidity and mortality worldwide, with a significantly higher prevalence among men than women. However, the incidence, clinical characteristics, and specific treatment of laryngeal cancer in women have often been overlooked by research. This review [...] Read more.
Laryngeal cancer is one of the main causes of morbidity and mortality worldwide, with a significantly higher prevalence among men than women. However, the incidence, clinical characteristics, and specific treatment of laryngeal cancer in women have often been overlooked by research. This review aims to examine gender differences in incidence, risk factors, hormonal mechanisms, survival, and therapeutic approaches for laryngeal cancer in women. Although smoking and alcohol remain the main risk factors, evidence suggests that women may be more vulnerable to the harmful effects of these behaviors, with a relative higher risk than men. In addition, hormonal factors such as estrogen may influence women’s susceptibility to laryngeal cancer, accelerating tumor growth and complicating treatment. Differences in treatment between the sexes, with women tending to receive less intensive treatment than men, is another crucial aspect that needs more attention. This article also analyses the disparities in survival, highlighting that women often have a better prognosis, although this trend varies according to demographic characteristics and the health system. The increasing incidence of laryngeal cancer in women requires increased research to fully understand risk factors and underlying biological mechanisms in order to develop more personalized treatments and optimize clinical outcomes for patients. Full article
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<p>PRISMA 2020 flow diagram of study selection process of the literature.</p>
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<p>Psychological impact of laryngeal cancer on women.</p>
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<p>Summary of characteristics of laryngeal carcinoma in women.</p>
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10 pages, 677 KiB  
Article
Impact of Age and Sex on Viral Load in Hepatitis C Virus Infection
by Andrea Magri, Giulia Francesca Manfredi, Carlo Smirne, Silvia Pigni, Michela Emma Burlone, Mattia Bellan, Nicole Vercellino, Rosalba Minisini and Mario Pirisi
Viruses 2025, 17(1), 21; https://doi.org/10.3390/v17010021 - 27 Dec 2024
Viewed by 481
Abstract
The determinants of hepatitis C virus (HCV) viral load remain incompletely understood and may differ in females, who are relatively protected from the consequences of HCV infection during their reproductive years. We aimed to evaluate how age affects the relationship between sex and [...] Read more.
The determinants of hepatitis C virus (HCV) viral load remain incompletely understood and may differ in females, who are relatively protected from the consequences of HCV infection during their reproductive years. We aimed to evaluate how age affects the relationship between sex and viral load. n = 922 patients (males n = 497, median age 62 years), all naïve to direct antiviral agents, were studied. Females were older (median age 68 vs. 57, p < 0.001) and had a higher prevalence of genotype 2 (33% vs. 20%, p < 0.001) than males; there was no difference between sexes regarding the METAVIR stage. The median HCV RNA concentration was 1.017 × 106 IU/mL (interquartile range, 0.286–2.400). Among males, the METAVIR stage was the strongest independent predictor of a high viral load (defined as the highest two quartiles), with advanced stages inversely associated with viral load (p = 0.008). In females, age was the only independent predictor, with women aged ≥55 years exhibiting higher loads (p = 0.009). These findings are consistent with data showing that estrogens exert an antiviral effect in in vitro models of HCV. Their declining levels after the menopause may explain the “catch-up” phase of HCV-related liver disease, observed in older women. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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<p>Distribution of log-transformed HCV RNA values of male and female patients, equal to or above 55 years (<b>a</b>) and below 55 years (<b>b</b>).</p>
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16 pages, 21287 KiB  
Article
Comparative Transcriptome Analysis of Gene Expression Between Female and Monoecious Spinacia oleracea L.
by Yingjie Zhao, Zhiyuan Liu, Hongbing She, Zhaosheng Xu, Helong Zhang, Shaowen Zheng and Wei Qian
Genes 2025, 16(1), 24; https://doi.org/10.3390/genes16010024 - 27 Dec 2024
Viewed by 569
Abstract
Background: Spinach (Spinacia oleracea L.) is an important leafy vegetable with dioecious and occasional monoecious plants. Monoecious lines are more suitable for hybrid production than dioecious lines due to their extended flowering period. However, genetic research on the sex determination of monoecism [...] Read more.
Background: Spinach (Spinacia oleracea L.) is an important leafy vegetable with dioecious and occasional monoecious plants. Monoecious lines are more suitable for hybrid production than dioecious lines due to their extended flowering period. However, genetic research on the sex determination of monoecism remains limited. Methods: In this study, RNA-seq analysis of monoecious and female spinach plants was performed at two distinct flowering stages. In total, we identified 4586 differentially expressed genes (DEGs), which were primarily involved in biological processes such as hormone signaling, cell wall biosynthesis, photosynthesis, and flower development, based on Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Among these DEGs, 354 transcription factors, including 27 genes associated with the ABCDE gene, were discovered. Furthermore, a co-expression gene regulatory network was built, identifying nine key genes that play important roles in regulating sex differentiation between female and monoecious plants. Conclusions: Our findings provide crucial molecular insights into the mechanisms of monoecism in spinach and offer a scientific basis for future spinach breeding. Full article
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<p>Sampling time periods of Sp139 and Sp140. (<b>a</b>) First day of flowering in Sp139; (<b>b</b>) first day of flowering in Sp140; (<b>c</b>) eighth day of flowering in Sp139; and (<b>d</b>) eighth day of flowering in Sp140.</p>
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<p>Repeated correlation assessment and PCA. (<b>a</b>) Pearson correlation coefficients for comparisons among all samples and (<b>b</b>) PCA based on all expressed genes, showing three distinct sample groups.</p>
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<p>Identification of DEGs in different comparison groups. (<b>a</b>) Number of up- and downregulated DEGs in four comparisons and (<b>b</b>) Venn diagram of DEGs in four comparisons between monoecious and female plants.</p>
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<p>qRT-PCR was performed using four major genes. (<b>a</b>) Relative expression of <span class="html-italic">SOV2g030600</span>; (<b>b</b>) <span class="html-italic">SOV6g032730</span>; (<b>c</b>) <span class="html-italic">SOV3g046810</span>; and (<b>d</b>) <span class="html-italic">SOV2g009980</span>.</p>
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<p>Top-20 pathways in the GO enrichment analysis of DEGs in five comparisons. (<b>a</b>) GO enrichment dot plot of Biological_Processes; (<b>b</b>) Cell_Components; (<b>c</b>) Molecular_Function; (<b>d</b>) GO terms and hierarchical relationship of Biological_Processes; (<b>e</b>) Cell_Components; and (<b>f</b>) Molecular_Function. Note: Each node represents a GO term, and the box represents the GO with an enrichment level of Top 5. The depth of the box (or ellipse) color represents the enrichment level, and the darker the color, the higher the significance. The name of the term and the q-value of the enrichment analysis are displayed on each node.</p>
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<p>Top-20 pathways in KEGG enrichment analysis of DEGs in 5 comparisons.</p>
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<p>DEGs on the first and eighth day of flowering. (<b>a</b>) Top-20 pathways analyzed for KEGG enrichment of 102 DEGs in AvsB and (<b>b</b>) 113 DEGs in CvsD.</p>
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<p>K-means clustering was used to group the expression profiles of the transcriptome into 12 clusters. Gene numbers are shown in each box. The light-gray background represents the individual expression profiles of genes within each cluster, while the blue line in the foreground depicts the overall dynamic expression trends fitted to the sample data.</p>
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23 pages, 37713 KiB  
Article
Adropin/Tirzepatide Combination Mitigates Cardiac Metabolic Aberrations in a Rat Model of Polycystic Ovarian Syndrome, Implicating the Role of the AKT/GSK3β/NF-κB/NLRP3 Pathway
by Islam Ibrahim Hegab, Hemat El-sayed El-Horany, Rania Nagi Abd-Ellatif, Nahla Anas Nasef, Asmaa H. Okasha, Marwa Nagy Emam, Shereen Hassan, Walaa S. Elseady, Doaa A. Radwan, Rasha Osama ElEsawy, Yasser Mostafa Hafez, Maha Elsayed Hassan, Nouran Mostafa Mansour, Gamaleldien Elsayed Abdelkader, Mohamed H. Fouda, Amira M. Abd El Maged and Hanan M. Abdallah
Int. J. Mol. Sci. 2025, 26(1), 1; https://doi.org/10.3390/ijms26010001 - 24 Dec 2024
Viewed by 629
Abstract
Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female [...] Read more.
Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3β), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1β and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-κB, Bcl2, and BAX were assessed. Our results displayed that adropin and/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3β/NF-κB/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications. Full article
(This article belongs to the Section Biochemistry)
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Figure 1

Figure 1
<p>Impact of adropin and/or Tirze on blood glucose, serum insulin, HOMA/IR, and both hormonal and lipid profiles. (<b>A</b>) Blood glucose level (mg/dL), (<b>B</b>) HOMA-IR, (<b>C</b>) Hormonal profile and (<b>D</b>) Lipid profile. Data are represented as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test, SPSS computer program. CON: control; Trize: tirzepatide; HOMA/IR: homeostasis model assessment of insulin resistance; LH: luteinizing hormone; HDL: High-density lipoprotein. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>Impact of adropin and/or Tirze on cardiac levels of p-AKT, p-GSK-3β, IL-1β, and IL-18 and relative NLRP3 expression. (<b>A</b>); Cardiac AKT level (ng/mg protein), (<b>B</b>): Cardiac p-GSK-3β (pg/mg protein), (<b>C</b>): Cardiac relative NLRP3 expression and (<b>D</b>) Cardiac IL-1β and IL-18 levels (pg/mg protein). Data are represented as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test, SPSS computer program. CON: control; Trize:tirzepatide; p-AKT: phosphorylated protein kinase B; p-GSK-3β: phosphorylated glycogen synthase kinase-3β; NLRP3: NOD-like receptor family pyrin domain containing 3; IL-1β: interleukin-1β; IL-18: interleukin-18. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>Impact of adropin and/or Tirze on cardiac TAC, MDA, and nitrite. (<b>A</b>) Cardia TAC (nmol/mg protein), (<b>B</b>) Cardiac MDA level (nmol/g tissue) and (<b>C</b>) Cardiac nitrite level (nmol/g tissue). Data are represented as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test, SPSS computer program. CON: control; Trize: tirzepatide; TAC: total antioxidant capacity; MDA: Malondialdehyde. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05), and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>Impact of adropin and/or Tirze on cardiac levels of GRP78, CHOP, and cleaved caspase-3 and relative expression of GRP78 and CHOP. (<b>A</b>) Cardiac GRP78 level (μg/mg protein), (<b>B</b>) Cardiac CHOP level (pg/mg protein), (<b>C</b>) Cardiac relative GRP78 &amp; CHOP expression and (<b>D</b>) Cardiac cleaved caspase-3 level (U/mg protein)Data are represented as mean ± standard deviation. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test, SPSS computer program. CON: control; Trize: tirzepatide; GRP78: glucose-regulated protein 78; CHOP: C/EBP homologous protein. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>Sections of ovaries stained with H&amp;E. (<b>A</b>) <b>CON Group</b> displaying normal ovarian architecture. The cortex reveals multiple primary follicles (PF), secondary follicles (SF), antral follicles (AF), Graafian follicles (GF), and average-sized corpora lutea (CL). Small blood vessels (BV) could be seen in the ovarian medium. (<b>B</b>) <b>PCOS group</b> showing multiple cystic follicles (CF), few growing follicles (arrows), one corpus luteum (CL), atretic follicles (AT), and degenerated follicles (DF). Hemorrhage (Hg) is seen between the follicles. (<b>C</b>) <b>The PCOS + Adropin group</b> showing a few cystic follicles (CF), many growing follicles (arrows), and corpora lutea (CL). However, degenerated follicles (DF) and hemorrhage (Hg) are noticeable. (<b>D</b>) <b>PCOS + Tirze Group</b> demonstrating an increased number of corpora lutea (CL), developing follicles (arrows), and fewer cystic follicles (CF). However, hemorrhage (Hg) and degeneration follicles (DF) are detected. (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> has several mature Graafian follicles (GF), developing follicles (arrows), and corpora lutea (CL). There are very few cystic (CF) and atretic follicles (AF). [Magnification ×40 scale bar = 500 µm]. (<b>F</b>) A column graph showing the mean number of growing follicles in the studied groups. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>At a higher magnification. (<b>A</b>) <b>CON Group</b> showing a mature Graafian follicle (GF) with an oocyte (O) surrounded by a thick granulosa layer (star) and thin theca cell layer (arrow). Several secondary follicles (SF) and corpora lutea (CL) could be seen. (<b>B</b>) <b>PCOS Group</b> showing multiple cystic follicles (CF) that are lined by a thin granulosa layer (star) and a thick theca cell layer (arrows). Intraluminal desquamated granulosa cells (dotted arrow), degenerated corpus luteum (DF), and hemorrhage (Hg) between follicles are detected. (<b>C</b>) <b>PCOS + Adropin Group</b> depicting one cystic follicle (CF) with detached granulosa cells (dotted arrows) inside its lumen and bordered by theca (arrow) and partially thick granulosa (star) cell layers. Congested blood vessels (BV) and atretic follicles (AF) are notable. (<b>D</b>) <b>PCOS + Tirze Group</b> showing multiple corpora lutea (CL), secondary follicles (SF), and one cystic follicle (CF) surrounded by thick granulosa cell (star) and thick theca cell (arrow) layers. Congested blood vessels (BV) and atretic follicles (AF) could be seen. (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> showing multiple corpora lutea (CL) mature Graafian follicles (GF) bordered with an outside thin theca cell layer (arrow) and an inner thick granulosa cell layer (star). Yet, few degenerated follicles (DF) and mild congested blood vessels (BV) are still present. [Magnification ×100 scale bar = 200 µm]. (<b>F</b>) A column graph showing the mean thickness of the granulosa and theca cell layer in the studied groups. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p>Sections of hearts stained with H&amp;E. (<b>A</b>) <b>CON group</b> displaying longitudinally striated branching cardiomyocytes (arrows) with central oval vesicular nuclei (N) and acidophilic sarcoplasm as well as central oval vesicular nuclei (N). Blood capillaries (BV) and intercalated discs (dashed arrows) could be seen. (<b>B</b>) <b>The PCOS group</b> displaying disruption of some cardiac muscle fibers (thick arrows) that are widely separated from each other (stars). While some nuclei are pyknotic (yellow arrows), others are karyolitic (thin arrows). Many sarcoplasmic vacuolations (V). The blood vessels were dilated and congested (BV), and inflammatory cells (IN) were detected. (<b>C</b>) <b>PCOS + Adropin group</b> (thick arrow) demonstrating some atrophic and degraded fibers. In particular, the perivascular region exhibits cellular infiltration (IN) and congested blood vessels (BV). Observe the areas of localized sarcoplasmic vacuolations (V) and the karyolitic (thin arrow) and pyknotic (yellow arrow) nuclei. (<b>D</b>) <b>PCOS + Tirze group</b> demonstrating apparent normal cardiac muscles (thick arrows). Nevertheless, localized areas of sarcoplasmic vacuolations (V), slight congestion of blood vessels (BV), and a small number of mononuclear inflammatory cells (IN) are still observed. (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> displaying the maintenance of the heart muscles’ typical architecture, with almost regular cardiomyocytes (arrow) and an oval vesicular nucleus (N). [Magnification: 50 µm = ×400 scale bar]. (<b>F</b>) A column graph showing the mean diameter of cardiomyocytes in the studied groups. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p><b>NF-κB immunohistochemical stained myocardial sections from the studied groups.</b> (<b>A</b>) <b>CON Group</b> demonstrating a small number of cardiomyocytes with a moderately positive nuclear NF-κB immunoexpression (arrows). (<b>B</b>) <b>PCOS Group</b> showing that a large number of cardiomyocytes had nuclei with strong NF-κB nuclear immunoexpression (arrows). (<b>C</b>) <b>PCOS + Adropin Group:</b> has few cardiomyocytes with strong positive NF-κB immunoexpression (arrows). (<b>D</b>) <b>PCOS + Tirze Group:</b> had some cardiomyocytes with moderately positive NF-κB nuclear immunoexpression (arrows). (<b>E</b>) <b>PCOS + Adropin + Tirze group</b> depicting a small number of cardiomyocytes with moderately positive NF-κB nuclear immunoexpression (arrows). [Magnification: 50 µm = ×400 scale bar]. The intensity of the NF-κB nuclear immunoexpression is shown in higher magnification in the insert. (<b>F</b>) A column graph showing the mean color intensity of NF-κB immunostaining and its cardiac levels in the studied groups.<sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p><b>Bcl2 immunohistochemical stained myocardial sections.</b> (<b>A</b>) <b>CON Group</b> displaying several cardiomyocytes with significant positive Bcl2 cytoplasmic immunoexpression (arrows). (<b>B</b>) <b>PCOS group</b> displaying cardiomyocytes with slightly positive Bcl2 cytoplasmic immunoexpression (arrows). (<b>C</b>) <b>PCOS + Adropin Group</b> depicting some cardiomyocytes with faint Bcl2 positive cytoplasmic immunoexpression (arrows). (<b>D</b>) <b>PCOS + Tirze group</b> demonstrating some cardiomyocytes with moderately Bcl2 positive cytoplasmic immunoexpression (arrows). (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> revealing several cardiomyocytes with moderately positive cytoplasmic Bcl2 immunoexpression (arrows). [Magnification: 50 µm = ×400 scale bar]. The intensity of the Bcl2 immunoexpression is shown at higher magnification in the insert. (<b>F</b>) A column graph showing the mean area percentage of Bcl2 immunostaining and its cardiac levels in the studied groups. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p><b>Bax immunostaining.</b> (<b>A</b>) <b>CON group:</b> has a small number of cardiomyocytes with faint positive cytoplasmic Bax immunoexpression (arrows). (<b>B</b>) <b>PCOS Group</b> showing many cardiomyocytes with strongly positive Bax cytoplasmic immunoexpression (arrows). (<b>C</b>) <b>PCOS + Adropin Group</b> illustrating some cardiomyocytes with a somewhat strong Bax cytoplasmic immunoexpression (arrows). (<b>D</b>) <b>PCOS + Tirze Group</b> showing few cardiomyocytes with moderately positive Bax cytoplasmic immunoexpression (arrows). (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> displaying cardiomyocytes with weak positive Bax cytoplasmic immunoreaction (arrows). [Magnification: 50 µm = ×400 scale bar]. The intensity of the Bax immunoexpression is shown at higher magnification in the insert. (<b>F</b>) A column graph showing the mean area percentage of Bax immunostaining and its cardiac levels in the studied groups. <sup>a</sup> Significance versus CON group (<span class="html-italic">p</span> &lt; 0.05), <sup>b</sup> Significance versus PCOS group (<span class="html-italic">p</span> &lt; 0.05), <sup>c</sup> Significance versus PCOS + adropin group (<span class="html-italic">p</span> &lt; 0.05) and <sup>d</sup> Significance versus PCOS + Tirze group (<span class="html-italic">p</span> &lt; 0.05). n = 6 rats/each group.</p>
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<p><b>Electron micrographs of rat myocardium.</b> (<b>A</b>) <b>CON Group</b> displaying a solitary euchromatic nucleus in a cardiomyocyte (N). Typical transverse myofibril striations consisting of dark (A) and light (I) bands divided by Z lines. Sarcomeres (S) are visible in the space between two consecutive Z-lines. Rows of mitochondria are located between the myofibrils and in the perinuclear region and, (M). (<b>B</b>) <b>PCOS Group</b> displaying a cardiomyocyte with a bizarre indented nucleus (N). Sarcomeres (S) lack their regular orientation. Swollen irregularly arranged mitochondria (M) as well as focal sarcoplasmic and perinuclear vacuolations (V) are noticeable. (<b>C</b>) <b>The PCOS + Adropin group</b> depicts a small nucleus in a cardiomyocyte (N) and regular transverse myofibril striations (thin arrows). However, focal lysis of cardiac myofibrils (thick arrow), few ruptured mitochondria (M), and focal sarcoplasmic vacuoles (V) are seen. (<b>D</b>) <b>PCOS + Tirze Group</b> demonstrates a euchromatic nucleus in cardiomyocyte (N) and focal lysis of cardiac myofibrils (thick arrows). (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> displays a cardiomyocyte with what seems to be regular transverse striations (thin arrows) and a sizable solitary euchromatic nucleus (N). Nevertheless, few myofibrils still depict focal areas of destruction (thick arrows). [Magnifications ×2500 scale bar =2 µm].</p>
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<p>At a higher magnification. (<b>A</b>) <b>CON group</b> presentation step-like appearance of the three components of the intercalated discs, namely the desmosomes (thick arrow), fascia adherents (dashed arrow), and gap junction (double arrows), in between the myofibrils. (<b>B</b>) <b>PCOS Group</b> showing markedly interrupted and disfigured intercalated discs (arrows). (<b>C</b>) <b>PCOS + Adropin group</b> depicting step-like intercalated discs (arrows) with areas of dilatations (thick arrows). (<b>D</b>) <b>PCOS + Tirze Group</b> revealing step-like intercalated discs (arrows) with areas of interruption (thick arrows). (<b>E</b>) <b>PCOS + Adropin + Tirze Group</b> showing a normal step-like appearance of the three components of the intercalated discs (arrows). [Magnifications ×6000 scale bar = 1 µm].</p>
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