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11 pages, 2718 KiB  
Case Report
Advances in the Diagnosis of Atypical Polypoid Adenomyoma Combining Immunohistochemical and Molecular-Based Approaches: Case Report and Review of the Literature
by Francisco Javier Azúa-Romeo, Sonia Bayona-Morón, Irene Rodriguez-Perez and Bárbara Angulo-Biedma
Curr. Issues Mol. Biol. 2024, 46(12), 14204-14214; https://doi.org/10.3390/cimb46120850 (registering DOI) - 17 Dec 2024
Viewed by 172
Abstract
Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of [...] Read more.
Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC). The distinction is essential for offering to patients a conservative treatment compared to the radical management required for endometrial cancer, a critical issue for the significant physical and psychological consequences that one procedure or another can have on women’s health. We performed a meta-analysis of the immunohistochemical markers used for the histological diagnosis of APA, comparing it with our case study. The evaluated markers were beta-catenin, h-caldesmon, desmin, vimentin, smooth muscle alpha-actin, CD10, Ki67, estrogen receptor (ER), progesterone receptor (PR), pan-cytokeratin, PTEN, PMS2, MSH2, MSH6, p53, MLH1, and p16. Discrepancies were observed in the expression of CD10, h- caldesmon, and p16 when comparing APA with EC. The results of the case evaluated by our team showed beta-catenin nuclear expression and positive immunostaining for pan-cytokeratin, ER, and PR in the glands; smooth muscle actin and desmin positive expression in stromal muscle; and p16 positive immunostaining in squamous morules. Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology. Full article
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<p>(<b>A</b>) Morular, stromal, and glandular area observed (H-E augmentation, 22.50×). (<b>B</b>) Actin positive immunostaining of the stroma highlighted (Augmentation 7.90×). (<b>C</b>) Keratin AE1–AE3 positivity for glandular lining cells and complete staining of the morula (augmentation, 11.85×). (<b>D</b>) p16 positive immunoexpression exclusively in morules (augmentation, 11.85×). (<b>E</b>) ER positive in glandular epithelium and intense, weak, or absent stroma in morules (augmentation, 11.85×). (<b>F</b>) PR-positive immunostaining in glandular epithelium, sparse in stroma and absent in morules (augmentation, 7.90×).</p>
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13 pages, 1292 KiB  
Article
Evaluating the Role of CBC-Derived Indices in Children with Hashimoto’s Thyroiditis
by Andrei-Ioan Munteanu, Iulius Jugănaru, Delia-Maria Nicoară, Niculina Mang, Raluca Vasilescu, Giorgiana-Flavia Brad, Alexandra-Cristina Scutca, Raluca Asproniu, Lucian-Ioan Cristun and Otilia Mărginean
Diagnostics 2024, 14(24), 2834; https://doi.org/10.3390/diagnostics14242834 (registering DOI) - 17 Dec 2024
Viewed by 195
Abstract
Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disorder characterized by chronic inflammation of the thyroid gland. Recent evidence indicates that the inflammation may extend beyond the thyroid. The study aims to explore the potential of complete blood count (CBC)-derived indices as markers of [...] Read more.
Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disorder characterized by chronic inflammation of the thyroid gland. Recent evidence indicates that the inflammation may extend beyond the thyroid. The study aims to explore the potential of complete blood count (CBC)-derived indices as markers of systemic inflammation in HT. Materials and Methods: This cross-sectional retrospective study from 1 January 2015, to 31 December 2023 included 147 pediatric HT patients and 144 apparently healthy controls. Thyroid profiles, antibodies, CBC, and protein electrophoresis data were collected from patient records. CBC-derived indices were calculated and compared between the HT and control groups, as well as among HT subgroups. Results: The median age of HT patients was 13.6 years (range: 11.2–15.5 years), with 66% being girls. The control group had a similar age and gender distribution, with a median age of 13.7 years (range: 11–15.8 years) and 70.8% girls. Of the HT patients, 50% had subclinical HT, 15% were euthyroid, and 34% had overt thyroid dysfunction. HT patients showed significantly higher neutrophil and lymphocyte counts, as well as all evaluated CBC-derived indices than controls (p < 0.001)). These differences were not significant among HT subgroups. Logistic regression indicated a strong association between an elevated neutrophil-to-lymphocyte ratio (NLR) and HT diagnosis (p < 0.001), while ROC analysis confirmed NLR as the most accurate CBC-derived marker for distinguishing HT from controls. Conclusions: Elevated NLR levels in pediatric HT patients provide additional evidence that inflammation may extend beyond the thyroid gland. These results support the potential of NLR as a reliable and accessible biomarker for evaluating inflammation in Hashimoto’s thyroiditis. Full article
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<p>Schematic representation of the HT patient selection process. T1DM, type 1 diabetes mellitus; LES, systemic lupus erythematosus; JIA, juvenile idiopathic arthritis; GN, glomerulonephritis.</p>
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<p>Correlation between CBC parameters and indices and HT diagnosis. HT, Hashimoto’s thyroiditis; NLR, neutrophil/lymphocyte ratio; PLR, platelet/lymphocyte ratio; SII, systemic inflammation index; SIRI, systemic inflammation response index. The significance levels were marked as *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, and * <span class="html-italic">p</span> &lt; 0.05. The accompanying figure employs a color gradient to depict significance levels, with darker shades representing more substantial associations and lighter shades indicating lesser degrees of statistical significance.</p>
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<p>Receiver operating characteristic curve analysis for evaluating the performance of (<b>a</b>) NLR, (<b>b</b>) PLR, (<b>c</b>) SII, and (<b>d</b>) SIRI in discriminating HT patients from controls.</p>
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6 pages, 6320 KiB  
Interesting Images
Misleading Imaging Findings: Bilateral Mylohyoid Defect Presenting as a Submandibular Mass Due to Sublingual Gland Protrusion
by Dagnija Grabovska, Junsiyuan Li, Maija Radziņa and Arturs Balodis
Diagnostics 2024, 14(24), 2833; https://doi.org/10.3390/diagnostics14242833 (registering DOI) - 16 Dec 2024
Viewed by 319
Abstract
Background/Objectives: The muscular base of the oral cavity is formed of the mylohyoid muscle, which forms a sling inferior to the tongue. The muscle is often discontinuous, and defects may include salivary tissues, fat, and/or blood vessels. Hypertrophic sublingual glands located in mylohyoid [...] Read more.
Background/Objectives: The muscular base of the oral cavity is formed of the mylohyoid muscle, which forms a sling inferior to the tongue. The muscle is often discontinuous, and defects may include salivary tissues, fat, and/or blood vessels. Hypertrophic sublingual glands located in mylohyoid defects can be herniated into bilateral submandibular spaces and present as palpable masses. The etiology of this condition may be congenital or acquired, and although such anatomical variations are common, they often go unrecognized in clinical practice. Sialoceles are cyst-like structures that result from chronic inflammation or ductal injury, indicating underlying problems with drainage efficiency. Methods: In this case series, we present two patients. Results: The first patient is a 44-year-old female who presented with a slowly enlarging right submandibular mass for two years, while the second is a 70-year-old female who presented with nonspecific neck discomfort, lacking palpable masses. In both, initial imaging (ultrasound and CT) was inconclusive. MRI revealed right sublingual gland herniation through a mylohyoid defect (mylohyoid boutonniere) in both cases. Conclusions: This highlights the importance of comprehensive imaging in the diagnosis of submandibular masses and emphasizes the need for considering mylohyoid boutonniere in cases of bilateral submandibular masses. Further research is warranted into the sialoceles associated with salivary gland abnormalities. Full article
(This article belongs to the Special Issue Advances in Oral and Maxillofacial Radiology)
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<p>First patient: A 44-year-old female patient who experienced a slowly enlarging mass in the right submandibular region for two years; the mass was painless, mobile and firm, accompanied by no other significant complaints. Initial evaluation included an ultrasound examination, which revealed a mass in the right submandibular area; however, the precise diagnosis remained elusive, and the pathology was not correctly identified. Following an inconclusive ultrasound, a CT scan with intravenous contrast was performed. However, the underlying pathology remained unidentified, probably due to a lack of recognition of the mylohyoid muscle defect. (<b>A</b>) In the CT scan, an axial view shows a defect in the right mylohyoid muscle (M) located in its anterior third, which measures approximately 8–9 mm. There is a pronounced herniated sublingual salivary gland (S) with complete protrusion of the gland, which has caused the patient discomfort for the past two years. This condition manifested as a palpable mass and a sensation of discomfort. (<b>B</b>) This image provides an enhanced visualization of the location of the right mylohyoid defect (<b>*</b>) and the complete protrusion of the right sublingual salivary gland (S). In this image, the defect (<b>*</b>) in the right mylohyoid muscle (M) is more clearly delineated, allowing a better understanding of its anatomical context. The sublingual salivary gland (S) is prominently visible, fully protruding through the defect (<b>*</b>), which emphasizes the extent of the herniation. This clear visual representation helps to assess the condition and understand the relationship between the mylohyoid defect (<b>*</b>) and the protruding gland, which has contributed to the symptoms of the patient. S—sublingual gland; M—mylohyoid muscle; *—mylohyoid muscle defect; GG—genioglossus muscle; SM—submandibular gland; H—hyoid bone. Subsequently, the first patient underwent magnetic resonance imaging (MRI) of the soft tissues of the neck with intravenous contrast administration. The muscular base of the oral cavity is formed of the mylohyoid muscle, which forms a sling inferior to the tongue. It is inserted into the slightly obliquely oriented mylohyoid line on the middle surface of the mandible, with the posterior aspect more cranial than the anterior aspect. The muscle is thickest in the posterior region and thin when approaching the mental tubercle [<a href="#B1-diagnostics-14-02833" class="html-bibr">1</a>]. In fact, the muscle is often discontinuous. Anatomical and surgical literature has shown that defects may include sublingual or submandibular salivary tissues, fat, blood vessels, or all three components [<a href="#B2-diagnostics-14-02833" class="html-bibr">2</a>]. As described in the literature, hypertrophic sublingual glands located in mylohyoid defects can be herniated into bilateral submandibular spaces and present as palpable masses [<a href="#B2-diagnostics-14-02833" class="html-bibr">2</a>,<a href="#B3-diagnostics-14-02833" class="html-bibr">3</a>]. Most mylohyoid muscle defects are less than 5 mm, but may occasionally be greater than 2 cm. Consequently, larger herniations can be mistaken both clinically and radiologically for pathological abnormalities [<a href="#B4-diagnostics-14-02833" class="html-bibr">4</a>]. The etiology of this condition may be congenital or acquired, and although such anatomical variations are not uncommon and can be found in almost every fifth individual using ultrasound, they often go unrecognized in clinical practice [<a href="#B4-diagnostics-14-02833" class="html-bibr">4</a>]. Sialoceles are cyst-like structures that result from the obstruction of saliva drainage, often due to chronic inflammation or ductal injury. They are associated with conditions that restrict normal salivary function, indicating underlying problems with drainage efficiency [<a href="#B5-diagnostics-14-02833" class="html-bibr">5</a>]. In this case series, we present two patients. In both, the initial imaging (ultrasound and CT) was inconclusive. MRI revealed right sublingual gland herniation through a mylohyoid defect (mylohyoid boutonniere) in both cases. This highlights the importance of comprehensive imaging, especially MRI, in the diagnosis of submandibular masses to avoid unnecessary interventions and emphasizes the need for considering mylohyoid boutonniere in cases of bilateral submandibular masses. Further research is warranted into the management of sialoceles associated with salivary gland abnormalities.</p>
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<p>(<b>A</b>) An MRI T1 TSE Dixon axial sequence showing a defect in the right mylohyoid muscle (M), accompanied by the protrusion of the right sublingual salivary gland (S). (<b>B</b>) A closer view using the same T1 TSE Dixon axial sequence, highlighting the protrusion of the right sublingual salivary gland (S), with several small sialoceles indicated by an arrow in the background, suggesting a chronic process. Sialoceles occur in the context of mylohyoid boutonnieres due to the displacement of the sublingual gland through a defect or gap in the mylohyoid muscle. This anatomical variation leads to the accumulation of saliva in the surrounding tissue, as the herniated gland may become obstructed or damaged. The mylohyoid muscle typically supports the sublingual gland, and when a boutonniere defect is present, the muscle’s integrity is compromised, allowing the gland to prolapse and potentially disrupt normal salivary drainage. As a result, saliva can collect in the tissues, forming a sialocele. This condition highlights the importance of understanding the anatomical relationships and variations in the submandibular region to avoid misdiagnosis and inappropriate management. Similar but less pronounced changes are observed on the left side, where there is a minor protrusion of the left sublingual salivary gland (S). It is notable that the signal intensity of both sublingual salivary glands (S) is similar, and the contrast is homogeneous, with no MRI findings suggesting malignancy. S—sublingual gland; M—mylohyoid muscle; *—mylohyoid muscle defect; GG—genioglossus muscle; SM—submandibular gland; SD—submandibular duct (also known as Wharton’s duct); HG—hyoglossus muscle; HY—hypoglossal nerve.</p>
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<p>(<b>A</b>) An MRI of the soft tissues of the neck with intravenous contrast administration of T2 TSE Dixon axial sequence, showing a defect in the right mylohyoid muscle (M), accompanied by the protrusion of the right sublingual salivary gland (S) with several small sialoceles indicated by an arrow in the background. Similar but less pronounced changes are observed on the left side, where there is a minor protrusion of the left sublingual salivary gland (S) with small sialocele (<b>arrow</b>). (<b>B</b>) A closer view of the defects in the right mylohyoid muscle (M) using the same T2 TSE Dixon axial sequence, highlighting the protrusion of the right sublingual salivary gland (S). Similar but less pronounced changes are observed on the left side, where there is a minor protrusion of the left sublingual salivary gland (S). S—sublingual gland; M—mylohyoid muscle; *—mylohyoid muscle defect; GG—genioglossus muscle; SM—submandibular gland; SD—submandibular duct (also known as Wharton’s duct); HG—hyoglossus muscle; HY—hypoglossal nerve.</p>
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<p>To clarify the changes, an ultrasound examination was performed. In the first image (<b>A</b>), the ultrasound examination, performed with a Canon Aplio i800 device, reveals a defect in the right mylohyoid muscle (M) measuring approximately 9 mm. This defect is associated with a protrusion of the right sublingual salivary gland (S), along with a protrusion of the right sublingual artery (ASL) through the muscle defect (*). In the second image (<b>B</b>), there is an observation of a defect (<b>*</b>) in the left mylohyoid muscle (M) measuring approximately 5 mm, accompanied by a small protrusion of the left sublingual salivary gland (S). These findings indicate significant anatomical changes in the sublingual region, highlighting the presence of muscle defects and glandular protrusions on both sides, which confirmed the diagnosis. S—sublingual gland; M—mylohyoid muscle; *—mylohyoid muscle defect; GG—genioglossus muscle; G—geniohyoid muscle; D—digastric muscle anterior belly; ASL—sublingual artery.</p>
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<p>The second patient: dual-energy contrast-enhanced CT neck. A 70-year-old female who presented with nonspecific neck discomfort, lacking palpable masses. Initial imaging (ultrasound and CT) was inconclusive. MRI revealed a right sublingual gland herniation through a mylohyoid defect (mylohyoid boutonniere). In fact, this stable lesion had been present, unrecognized, for three years based on prior imaging. The axial CT image (<b>A</b>) shows a moderately enhancing nodular structure (S) in the right submandibular space, with a narrowed neck extending through a defect of the mylohyoid muscle (<b>*</b>) into the sublingual space. Note a partially imaged venous malformation with phleboliths in the right submandibular space, an incidental finding. An iodine map (<b>B</b>) discovered that the nodular structure has same degree of enhancement as the contralateral sublingual gland and both submandibular glands. S: sublingual gland; SM: submandibular gland; M: mylohyoid muscle; *: boutonniere; G: geniohyoid muscle; GG: genioglossus muscle; H: hyoglossus muscle.</p>
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<p>Axial (<b>A</b>) and coronal (<b>B</b>) T1-weighted images show a right mylohyoid boutonniere (*) through which the hypertrophic right sublingual gland (S) herniates into the right submandibular space. S: sublingual gland; SM: submandibular gland; M: mylohyoid muscle; *: boutonniere; G: geniohyoid muscle; GG: genioglossus muscle; H: hyoglossus muscle; DG: anterior belly of digastric muscle.</p>
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<p>The two consecutive axial postcontrast T1-weighted fat-saturation images above (<b>A</b>) and below (<b>B</b>) show herniation of the right sublingual gland (S) through the right mylohyoid boutonniere (<b>*</b>) into the right submandibular space. The left sublingual gland is smaller in comparison. S: sublingual gland; SM: submandibular gland; M: mylohyoid muscle; *: Boutonniere; G: geniohyoid muscle; GG: genioglossus muscle; H: hyoglossus muscle.</p>
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10 pages, 1243 KiB  
Review
The Role of Scavenger Receptor BI in Sepsis
by Dan Hao, Jian-Yao Xue, Qian Wang, Ling Guo and Xiang-An Li
Int. J. Mol. Sci. 2024, 25(24), 13441; https://doi.org/10.3390/ijms252413441 - 15 Dec 2024
Viewed by 246
Abstract
Sepsis is a life-threatening condition resulting from a dysregulated host response to infection. Currently, there is no effective therapy for sepsis due to an incomplete understanding of its pathogenesis. Scavenger receptor BI (SR-BI) is a high-density lipoprotein (HDL) receptor that plays a key [...] Read more.
Sepsis is a life-threatening condition resulting from a dysregulated host response to infection. Currently, there is no effective therapy for sepsis due to an incomplete understanding of its pathogenesis. Scavenger receptor BI (SR-BI) is a high-density lipoprotein (HDL) receptor that plays a key role in HDL metabolism by modulating the selective uptake of cholesteryl ester from HDL. Recent studies, including those from our laboratory, indicate that SR-BI protects against sepsis through multiple mechanisms: (1) preventing nitric oxide-induced cytotoxicity; (2) promoting hepatic lipopolysaccharide (LPS) clearance and regulating cholesterol metabolism in the liver; (3) inhibiting LPS-induced inflammatory signaling in macrophages; and (4) mediating the uptake of cholesterol from HDL for inducible glucocorticoid (iGC) synthesis in the adrenal gland, which controls systemic inflammatory response. In this article, we review the roles of SR-BI in sepsis. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Sepsis)
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<p>The pathogenesis of sepsis. Upon infection, pattern recognition receptors (PRRs) on immune cells recognize and bind to specific microbial structures known as PAMPs or DAMPs. The activation of the innate immune system results in the release of cytokines/chemokines, nitric oxide, and oxygen radicals, and complement system activation. This process leads to coagulation due to endothelial damage and the rapid release of pro-inflammatory cytokines. The complement system and coagulation cascades subsequently reduce vascular stability and cause microvascular blockages, resulting in coagulation, fever, capillary leakage, and ultimately multiple-organ failure. These factors drive the typical inflammatory response underlying sepsis’ pathophysiology. LPS, lipopolysaccharide; LTA, lipoteichoic acid; PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; TLR4, toll-like receptor 4; TF, tissue factor; PAI-1, plasminogen activator inhibitor-1; IL-1, interleukin-1; TNF-1α, tumor necrosis factor-1 alpha; NO, nitric oxide.</p>
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<p>Summary of SR-BI protection against sepsis. SR-BI exerts its protective effect in sepsis through multiple mechanisms: (1) prevent NO-induced cytotoxicity; (2) mediate LPS clearance and cholesterol metabolism in liver; (3) suppress LPS-induced inflammatory signaling in macrophages; (4) mediate uptake of cholesterol from HDL for iGC synthesis in adrenal gland, which controls systemic inflammatory response.</p>
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12 pages, 3581 KiB  
Article
Biochemical Properties of the Acid Ectophosphatase Activity of Phytomonas serpens Involved in Cell Proliferation
by Luiz Fernando Carvalho-Kelly, Anita Leocadio Freitas-Mesquita, Thaís Souza Silveira Majerowicz and José Roberto Meyer-Fernandes
Kinases Phosphatases 2024, 2(4), 379-390; https://doi.org/10.3390/kinasesphosphatases2040024 (registering DOI) - 15 Dec 2024
Viewed by 215
Abstract
Phytomonas is the only kinetoplastid that can parasitize plants, causing economically relevant issues. Phytomonas serpens share similarities with pathogenic trypanosomatids, including surface enzymes that are involved in adhesion to the salivary gland of their experimental host, the insect Oncopeltus fasciatus. Ectophosphatases are [...] Read more.
Phytomonas is the only kinetoplastid that can parasitize plants, causing economically relevant issues. Phytomonas serpens share similarities with pathogenic trypanosomatids, including surface enzymes that are involved in adhesion to the salivary gland of their experimental host, the insect Oncopeltus fasciatus. Ectophosphatases are cell surface enzymes involved in host–parasite interactions that are widely distributed among microorganisms. This work aimed to perform the biochemical characterization of P. serpens ectophosphatase activity, investigating and discussing its possible physiological role. This activity presented an acidic profile, and its kinetic parameters Km and Vmax were calculated as 1.57 ± 0.08 mM p-NPP and 10.11 ± 0.14 nmol p-NP/(h × 108 flagellates), respectively. It was stimulated by cobalt, inhibited by zinc, and insensitive to EDTA, a divalent metal chelator. The inhibitor sodium orthovanadate was able to decrease P. serpens ectophosphatase activity and growth, suggesting its involvement in cell proliferation. Given that P. serpens can uptake inorganic phosphate (Pi) from the extracellular medium, it is likely that its ectophosphatase activity acts together with the transport systems in the Pi acquisition process. The elucidation of the molecular mechanisms involved in this process emerges as a relevant perspective, providing new strategies for controlling Phytomonas infection. Full article
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<p>Time course and flagellate density dependence of <span class="html-italic">Phytomonas serpens</span> ectophosphatase activity. Ectophosphatase activity is linear with both (<b>A</b>) time and (<b>B</b>) flagellate density ((<b>A</b>): r<sup>2</sup> = 0.987, <span class="html-italic">n</span> = 3; (<b>B</b>): r<sup>2</sup> = 0.991, <span class="html-italic">n</span> = 3), thus validating the use of intact flagellates to assess ectophosphatase activity.</p>
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<p>Phosphatase activity of intact cells and the supernatant of <span class="html-italic">Phytomonas serpens</span>. Intact cells were incubated for 60 min at 25 °C in the reaction buffer in the absence of the substrate <span class="html-italic">p</span>-NPP. After this time, the cells were centrifuged, and aliquots of the cells and supernatant were assayed for ectophosphatase activity (<span class="html-italic">n</span> = 3). The asterisk denotes significant difference (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of pH on the ectophosphatase activity of <span class="html-italic">Phytomonas serpens</span>. All pH values were tested with the same buffering system (10 mM each MES/HEPES/TRIS) to guarantee both cell integrity and buffering capacity from pH 5.0 to 8.0. The ectophosphatase activity is acidic, although it was not possible to observe its optimum pH because of the need to keep microorganisms intact during all the assays. Black circles represent means ± standard errors (<span class="html-italic">n</span> = 3). In some cases, standard errors are graphically smaller than symbols.</p>
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<p>Effect of <span class="html-italic">p</span>-NPP concentration on the ectophosphatase activity of <span class="html-italic">Phytomonas serpens</span>. The first and second points of the ectophosphatase activities were measured within 30 min to ensure that <span class="html-italic">p</span>-NPP hydrolysis did not exceed 10% of the available substrate; other concentrations were assayed for 60 min. Black circles represent means ± standard errors (<span class="html-italic">n</span> = 3), and experimental data fitting shows a nonlinear regression using the Michaelis–Menten equation. Calculated apparent kinetic parameters were <span class="html-italic">K</span><sub>m</sub> = 1.575 ± 0.077 mM <span class="html-italic">p</span>-NPP and <span class="html-italic">V</span><sub>max</sub> = 10.11 ± 0.137 nmol <span class="html-italic">p</span>-NP/(h × 10<sup>8</sup> flagellates).</p>
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<p>Effects of different metals on <span class="html-italic">Phytomonas serpens</span> ectophosphatase activity. The ectophosphate activity was inhibited by zinc and stimulated by cobalt; other metals tested could not modulate the activity. EDTA, a divalent cations chelator, had no effect on ectophosphatase activity, which suggests that this activity is not carried by a metalloenzyme (<span class="html-italic">n</span> = 3). EDTA and divalent metals were tested at a concentration of 1 mM. The asterisks denote significant differences (<span class="html-italic">p</span> &lt; 0.05) compared to the control.</p>
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<p>Effects of sodium orthovanatade on <span class="html-italic">Phytomonas serpens</span> ectophosphatase activity and growth. The ectophosphate activity was inhibited by 1 mM sodium orthovanadate ((<b>A</b>), <span class="html-italic">n</span> = 3); <span class="html-italic">P. serpens</span> proliferation was inhibited by 1 mM sodium orthovanadate from the second up to the fifth day of growth ((<b>B)</b> (<span class="html-italic">n</span> = 3). The asterisks denote significant differences (<span class="html-italic">p</span> &lt; 0.05) compared to the controls.</p>
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10 pages, 8466 KiB  
Article
Investigation of a Robust Blind Deconvolution Algorithm Using Extracted Structures in Light Microscopy Images of Salivary Glands: A Pilot Study
by Kyuseok Kim, Jae-Young Kim and Ji-Youn Kim
Electronics 2024, 13(24), 4940; https://doi.org/10.3390/electronics13244940 - 14 Dec 2024
Viewed by 360
Abstract
Although light microscopy (LM) images are widely used to observe various bodily tissues, including salivary glands, reaching a satisfactory spatial resolution in the final images remains a major challenge. The objective of this study was to model a robust blind deconvolution algorithm using [...] Read more.
Although light microscopy (LM) images are widely used to observe various bodily tissues, including salivary glands, reaching a satisfactory spatial resolution in the final images remains a major challenge. The objective of this study was to model a robust blind deconvolution algorithm using the extracted structure and analyze its applicability to LM images. Given LM images of the salivary glands, the proposed robust blind deconvolution method performs non-blind deconvolution after estimating the structural map and kernel of each image. To demonstrate the usefulness of the proposed algorithm for LM images, the perceptual sharpness index (PSI), Blanchet’s sharpness index (BSI), and natural image quality evaluator (NIQE) were used as evaluation metrics. We demonstrated that when the proposed algorithm was applied to salivary gland LM images, the PSI and BSI were improved by 7.95% and 7.44%, respectively, compared with those of the conventional TV-based algorithm. When the proposed algorithm was applied to an LM image, we confirmed that the NIQE value was similar to that of a low-resolution image. In conclusion, the proposed robust blind deconvolution algorithm is highly applicable to salivary gland LM images, and we expect that further applications will become possible. Full article
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<p>Simplified framework of a robust blind deconvolution method using a structural map to estimate the blur kernel in a light microscopy image.</p>
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<p>Low-resolution image of the salivary gland obtained via light microscopy (scale bar = 200 μm, <math display="inline"><semantics> <mrow> <mo>×</mo> </mrow> </semantics></math>100 magnification) (<b>top</b>), and restored images obtained by the total variation (TV)-based (<b>middle</b>) and proposed (<b>bottom</b>) algorithms. A distortion effect can be observed following restoration by the TV-based algorithm.</p>
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<p>Low-resolution image of the salivary gland obtained via light microscopy (scale bar = 50 μm, <math display="inline"><semantics> <mrow> <mo>×</mo> </mrow> </semantics></math>400 magnification) (<b>left</b>), and restored images obtained by the TV-based (<b>middle</b>) and proposed (<b>right</b>) algorithms. As a result of enlarging and observing areas where blurring occurred, it was confirmed that the TV-based algorithm incurs significant image distortion.</p>
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<p>(<b>a</b>) Perceptual sharpness index (PSI) and (<b>b</b>) Blanchet’s sharpness index (BSI) results measured from light microscopy images obtained for original images and reconstructions by the TV-based and proposed algorithms. Images reconstructed by the proposed algorithm exhibited superior PSI and BSI values compared to the original images and TV-based reconstructions.</p>
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<p>Natural image quality evaluator (NIQE) results measured from light microscopy images, obtained for original images and reconstructions by the TV-based and proposed algorithms. Although the original image exhibited the best NIQE results, the reconstruction obtained by the proposed algorithm also achieved excellent results.</p>
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17 pages, 3380 KiB  
Article
Eggshell Quality Traits and Transcriptome Gene Screening Between Yunnong and Jingfen Chicken Breeds
by Zijian Li, Hao Wu, Jing Fu, Maida Mushtaq, Muhammad Khan, Yong Liu, Zobia Azeem, Hongmei Shi, Yang He, Ru Zhang, Muhammad Aziz Ur Rahman, Jiajia Kang, Changrong Ge and Kun Wang
Biology 2024, 13(12), 1048; https://doi.org/10.3390/biology13121048 - 14 Dec 2024
Viewed by 467
Abstract
The eggshell quality traits in avian species, including Yunnong chickens (YN), are crucial for commercial and breeding purposes. The use of advanced biotechnologies, such as gene sequencing, has become increasingly common for identifying genetic markers and comparing specific traits in livestock. However, genetic [...] Read more.
The eggshell quality traits in avian species, including Yunnong chickens (YN), are crucial for commercial and breeding purposes. The use of advanced biotechnologies, such as gene sequencing, has become increasingly common for identifying genetic markers and comparing specific traits in livestock. However, genetic markers related to eggshell traits in YN chickens remain unexplored. This study aimed to compare eggshell quality traits and identify genetic markers in YN chickens versus commercial Jingfen chickens (JF). A total of 400 chicks (200 per breed) were reared for 300 days under controlled conditions. At the end, 60 eggs from each breed were analyzed using scanning electron microscopy to examine eggshell cross-sections and mammillary layer structure. Tissue samples from kidneys and eggshell glands were collected from six hens per breed for RT-qPCR analysis to study gene expression profiles. Results showed that YN chickens had significantly higher eggshell strength, thickness, mammillary density, and effective layer thickness than JF chickens (p < 0.01). Despite this, YN chickens had a thinner mammillary layer. RT-qPCR analysis confirmed five candidate genes related to eggshells (LSS, NSDHL, MSMO1, SQLE, and FDFT1) that play an important role in this process. Pathway analysis revealed significant enrichment in several biological processes, including steroid biosynthesis, glycerolipid metabolism, purine metabolism, and thiamine metabolism. Based on these results, the YN chickens have strong eggshells with better thickness, mammillary density, and effective layer thickness. In addition, genomic and pathways analysis suggest a complex interaction of metabolic, immune, and cellular processes potentially influencing eggshell quality traits in poultry. Full article
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<p>Cross-section microstructure of the YN chicken eggshell (<b>A</b>) and the JF chicken eggshell (<b>B</b>) at 500×. The larger area arrow represents the effective layer thickness, while the smaller one is the mastoid layer thickness.</p>
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<p>Microstructure of eggshell mammillary layer of the mastoid process of the YN chicken eggshell (<b>A</b>) and the JF chicken eggshell (<b>B</b>) at 500×.</p>
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<p>FPKM data expression density plot (<b>a</b>), density plot (<b>b</b>), and PCA cluster analysis plot (<b>c</b>) of kidney (JF_S, and YN_S) and eggshell gland (JF_ZG and YN_ZG) tissues of Yunnong and Jingfen chickens.</p>
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<p>Volcano plot of differentially expressed genes of Yunnong and Jingfen chicken breeds in kidney (JF–S and YN–S) and eggshell gland (JF–ZG and YN–ZG) tissues.</p>
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<p>Cluster map of differentially expressed genes between Yunnong and Jingfen chicken breeds in kidney (JF–S and YN–S) and eggshell gland (JF–ZG and YN–ZG) tissues.</p>
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<p>GO enrichment analysis between the YN–ZG_JF–ZG group (<b>a</b>) and the YN–S_JF–S group (<b>b</b>).</p>
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<p>Comparison between RT-qPCR and RNA-seq results for the eggshell glands (<b>A</b>) and kidney (<b>B</b>) tissues of the Yunnong and Jingfen chicken breeds.</p>
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14 pages, 2893 KiB  
Article
Role of Filter-Feeding Bivalves in the Bioaccumulation and Transmission of White Spot Syndrome Virus (WSSV) in Shrimp Aquaculture Systems
by Joon-Gyu Min, Young-Chul Kim and Kwang-Il Kim
Pathogens 2024, 13(12), 1103; https://doi.org/10.3390/pathogens13121103 - 13 Dec 2024
Viewed by 298
Abstract
White spot syndrome virus (WSSV) poses a major risk to shrimp aquaculture, and filter-feeding bivalves on shrimp farms may contribute to its persistence and transmission. This study investigated the bioaccumulation and vector potential of WSSV in Pacific oysters (Crassostrea gigas), blue [...] Read more.
White spot syndrome virus (WSSV) poses a major risk to shrimp aquaculture, and filter-feeding bivalves on shrimp farms may contribute to its persistence and transmission. This study investigated the bioaccumulation and vector potential of WSSV in Pacific oysters (Crassostrea gigas), blue mussels (Mytilus edulis), and manila clams (Venerupis philippinarum) cohabiting with WSSV-infected shrimp. Sixty individuals of each species (average shell lengths: 11.87 cm, 6.97 cm, and 5.7 cm, respectively) cohabitated with WSSV-infected shrimp (Penaeus vannamei, average body weight: 16.4 g) for 48 h. In the experiments, bivalves accumulated WSSV particles in both the gill and digestive gland tissues, with the digestive glands exhibiting higher viral load (average viral load, 3.91 × 104 copies/mg), showing that the viral concentrations in bivalve tissues are directly influenced by seawater WSSV concentrations, reaching levels sufficient to induce infection and 100% mortality in healthy shrimp using tissue homogenates. After a 168 h release period in clean water, the WSSV levels in bivalve tissues decreased below the detection thresholds, indicating reduced transmission risk. These results highlight the role of bivalves as temporary reservoirs of WSSV in aquaculture settings, with the transmission risk dependent on the viral concentration and retention period. Our findings suggest that the management of bivalve exposure in WSSV-endemic environments could improve the biosecurity of shrimp farms. Full article
(This article belongs to the Section Viral Pathogens)
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<p>Schematic of the cohabitation of shellfish with WSSV-infected shrimp. Each of 60 shellfish were cohabitated with 30 WSSV-infected shrimp (10<sup>5</sup> copies/shrimp). Shellfish harboring WSSV particles were transferred to a new 100 L tank for depuration at 23 °C. Sampling times are denoted by black triangles.</p>
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<p>Schematic of the cohabitation of shellfish with WSSV-infected shrimp. Each of 60 shellfish were cohabitated with 60 WSSV-infected shrimp (10<sup>5</sup> copies/shrimp). Shellfish harboring WSSV particles were transferred to a new 100 L tank for depuration at 23 °C. Sampling times are denoted by black triangles.</p>
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<p>WSSV genome copy numbers in seawater from infected whiteleg shrimp with cumulative mortality (%). The titer of waterborne WSSV (broken line) and daily mortality (line) in tanks injected with the Kr-1 (△) and Kr-4 (●) strains are shown.</p>
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<p>WSSV genome copy numbers in seawater from 30 infected whiteleg shrimp with cumulative mortality (%). The titer of waterborne WSSV (broken line) and daily cumulative mortality (line) in 100 L tanks injected with the Kr-4 strain are shown.</p>
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<p>Individual WSSV genome copy numbers in gills (<b>A</b>) and digestive glands (<b>B</b>) during the low-dose bioaccumulation of oysters (triangle), mussels (circle), and clams (square). Five shellfish were sampled at each time point, and viral copy numbers were determined via qPCR using two-step PCR-positive samples. Horizontal lines indicate the median value, and broken lines indicate the detection limit for all graphs. An asterisk indicates a significant difference (two-way ANOVA, * <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Individual WSSV copy numbers in gills (<b>A</b>) and digestive glands (<b>B</b>) during the depuration of oysters (triangle), mussels (circle), and clams (square). Five shellfish were sampled at each time point, and viral copy numbers were determined via qPCR using two-step PCR-positive samples. Horizontal lines indicate the median value, and broken lines indicate the detection limit for all graphs. An asterisk indicates significant difference (two-way ANOVA, * <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>WSSV genome copy numbers in seawater from infected whiteleg shrimp with cumulative mortality (%). The titer of waterborne WSSV (broken line) and daily mortality (line) in tanks injected with the Kr-4 strain are shown.</p>
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<p>Individual WSSV copy numbers in gills (<b>A</b>) and digestive glands (<b>B</b>) during the high-dose bioaccumulation of oysters (triangle), mussels (circle), and clams (square). Five shellfish were sampled at each time point, and viral copy numbers were determined via qPCR using two-step PCR-positive samples. Horizontal lines indicate the median value, and broken lines indicate the detection limit for all graphs. An asterisk indicates significant difference (two-way ANOVA, * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Individual WSSV copy numbers in gills (<b>A</b>) and digestive glands (<b>B</b>) during the depuration of oysters (triangle), mussels (circle), and clams (square). Five shellfish were sampled at each time point, and viral copy numbers were determined via qPCR using two-step PCR-positive samples. Horizontal lines indicate the median value, and broken lines indicate the detection limit for all graphs. An asterisk indicates significant difference (two-way ANOVA, * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Cumulative mortality (%) of whiteleg shrimp challenged with shellfish-derived WSSV. Digestive gland homogenates from WSSV-accumulated shellfish (2 days of cohabitation with WSSV-infected shrimp) and depurated shellfish (168 h of depuration after accumulation) were intraperitoneally injected (10 mg per shrimp) into five whiteleg shrimp. Symbols represent different shellfish species: oyster (▲), mussel (●), and clam (■). The dashed lines indicate accumulated (Acc.) samples, and the solid lines represent depurated (Dep.) samples.</p>
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16 pages, 1111 KiB  
Review
Thoracic Endometriosis Syndrome: A Comprehensive Review and Multidisciplinary Approach to Management
by Camran Nezhat, Nikki Amirlatifi, Zahra Najmi and Angie Tsuei
J. Clin. Med. 2024, 13(24), 7602; https://doi.org/10.3390/jcm13247602 - 13 Dec 2024
Viewed by 292
Abstract
Background: Endometriosis is a systemic, inflammatory, estrogen-dependent condition characterized by endometrial stroma and gland-like lesions outside of the uterus. It causes a range of symptoms, notably chronic pelvic pain, infertility and organ dysfunction. Thoracic endometriosis syndrome (TES) has been described as endometriosis that [...] Read more.
Background: Endometriosis is a systemic, inflammatory, estrogen-dependent condition characterized by endometrial stroma and gland-like lesions outside of the uterus. It causes a range of symptoms, notably chronic pelvic pain, infertility and organ dysfunction. Thoracic endometriosis syndrome (TES) has been described as endometriosis that is found in the lung parenchyma, pleura and diaphragm. It may be asymptomatic or present with symptoms of catamenial pneumothorax, hemothorax, hemoptysis, isolated chest pain, shoulder pain or findings of lung nodules. Aim: The aim of this review is to provide a comprehensive overview of thoracic endometriosis syndrome (TES), including its clinical presentation, diagnostic challenges, and current management strategies. This review aims to highlight the importance of a multidisciplinary approach in the treatment of TES, emphasizing conservative management and the role of minimally invasive surgical techniques for refractory cases. Conclusions: Thoracic endometriosis syndrome appears to be a marker of severe endometriosis. As much as possible, the patient with TES is managed conservatively, with surgery reserved for refractory cases. When surgery is recommended, the procedure is conducted through a multidisciplinary minimally invasive approach, with video-assisted thoracoscopic surgery (VATS) and video-assisted laparoscopy. Meticulous intraoperative survey, the removal of endometriosis implants with and without robotic assistance and post-operative hormonal therapy may be recommended to prevent recurrence. Full article
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<p>Options for management with TES.</p>
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<p>Diaphragmatic defects from endometriosis: (<b>A</b>) Superficial endometriosis and diaphragmatic defect. The figure shows superficial endometriosis and diaphragmatic defect; (<b>B</b>) Deep infiltrative endometriosis. The figure shows deep infiltrative endometriosis of the diaphragm.</p>
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<p>Endometriosis of the diaphragm, treatment with mesh.</p>
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26 pages, 1057 KiB  
Review
State of Knowledge About Thyroid Cancers in the Era of COVID-19—A Narrative Review
by Agnieszka Bronowicka-Szydełko, Maciej Rabczyński, Ilias Dumas, Żanna Fiodorenko-Dumas, Beata Wojtczak, Łukasz Kotyra, Irena Kustrzeba-Wójcicka, Łukasz Lewandowski, Beata Ponikowska, Aleksandra Kuzan, Joanna Kluz, Andrzej Gamian and Katarzyna Madziarska
Biomedicines 2024, 12(12), 2829; https://doi.org/10.3390/biomedicines12122829 - 13 Dec 2024
Viewed by 403
Abstract
Thyroid cancer (TC), due to its heterogeneous nature, remains a clinical challenge. Many factors can initiate the carcinogenesis process of various types of TC, which complicates diagnosis and treatment. The presented review gathers current information on specific types of TC, taking into account [...] Read more.
Thyroid cancer (TC), due to its heterogeneous nature, remains a clinical challenge. Many factors can initiate the carcinogenesis process of various types of TC, which complicates diagnosis and treatment. The presented review gathers current information on specific types of TC, taking into account the effects of the COVID-19 pandemic. It is likely that COVID-19 has influenced and continues to influence the function of the thyroid gland. A high percentage of patients with COVID-19 showing simultaneous pathological changes in the thyroid suggests that SARS-CoV-2 may disrupt the function of this gland and initiate pro-oxidative mechanisms, inflammatory states, and autoimmune diseases, thereby promoting the formation of neoplastic changes. Furthermore, changes in the expression of the ACE2, TMPRSS2, CLEC4M and DPP4 genes, observed in TC, also occur in COVID-19. Therefore, it is probable that the interaction of SARS-CoV-2 with thyroid cell receptors may initiate carcinogenesis in this gland. Additionally, some drugs used in TC therapy (e.g., levothyroxine) may increase the affinity of SARS-CoV-2 for cells, which could contribute to a more severe course of COVID-19 and the emergence of long-term symptoms (post-COVID-19). Moreover, the consequences of sanitary restrictions (limited access to medical services, reduction in endocrinological and oncological procedures) that took place in many countries during the COVID-19 pandemic may lead in the future to an increased number of missed diagnoses and the emergence of aggressive cancers. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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<p>Molecular pathways leading to thyroid carcinogenesis potentially influenced by SARS-CoV-2.</p>
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<p>Genes engaged in the SARS-CoV-2 infection and engaged in the TCs development.</p>
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10 pages, 1283 KiB  
Article
Endoscopic and Histological Characteristics of Gastric Cancer Detected Long After Helicobacter pylori Eradication Therapy
by Ryo Abe, Shu Uchikoshi, Yohei Horikawa, Nobuya Mimori, Yuhei Kato, Yuta Tahata, Saki Fushimi, Masahiro Saito and Satsuki Takahashi
Cancers 2024, 16(24), 4153; https://doi.org/10.3390/cancers16244153 - 13 Dec 2024
Viewed by 387
Abstract
Background/Objectives: Since 2013, eradication therapy for Helicobacter pylori gastritis (Hp-ET) has been covered by the National Health Insurance of Japan. Recently, the risk of post-eradication gastric cancer (pE-GC) has increased. pE-GC includes cancers that develop immediately and several years after Hp [...] Read more.
Background/Objectives: Since 2013, eradication therapy for Helicobacter pylori gastritis (Hp-ET) has been covered by the National Health Insurance of Japan. Recently, the risk of post-eradication gastric cancer (pE-GC) has increased. pE-GC includes cancers that develop immediately and several years after Hp-ET. Therefore, we aimed to clarify the endoscopic and histological characteristics of late types of pE-GCs. Method: One hundred patients with differentiated cancers detected after Hp-ET who underwent endoscopic submucosal dissection from 2015 to 2023 were compared. Patients were divided into two groups; the immediate group (n = 69), with cancer detected within 6 years, and the delayed group (n = 31), with cancer detected within >6 years after Hp-ET. The background mucosa and tumor mucosa were examined individually. The endoscopic findings were as follows: enlarged folds, map-like redness, intermediate zone irregularity, and the presence of a regular arrangement of collecting venules and a light blue crest (background); an irregular surface structure, an irregular vascular pattern, an irregular surface pattern, and a gastritis-like appearance (tumor). The histological findings were as follows: a low remnant rate of the fundic glands, intestinal metaplasia (IM), crypt enlargement, and neutrophil infiltration (background); mosaicism, the elongation of noncancer ducts, and an overlying non-neoplastic epithelium (tumor). Results: There was no significant difference regarding the background mucosa and tumor mucosa between the two groups. In the delayed group, the remnant rate of the fundic glands was 19.8 ± 15.6%, and IM was 87.1% (27/31). Further, 90.3% (28/31) of the patients exhibited persistent neutrophil infiltration. Conclusion: This study suggested that patients with a low remnant rate of the fundic gland and IM and persistent mucosal inflammation were at high risk for developing pE-GCs. Full article
(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)
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<p>Annual transitions of post-eradication gastric cancer treated with gastric ESD (total 100 cases).</p>
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<p>Flow diagram of patient enrollment.</p>
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<p>The remnant rate of the fundic glands. This was calculated by microscopically measuring the area of the fundic glands on the edge of the ESD specimen (1.0 mm × 2.0 mm).</p>
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<p>Annual transitions of remnant rate of fundus glands on background mucosa.</p>
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10 pages, 1966 KiB  
Article
PRAME Staining of Adnexal Lesions and Common Skin Cancer Types: Biomarker with Potential Diagnostic Utility
by Hisham F. Bahmad and John Alexis
Dermatopathology 2024, 11(4), 364-373; https://doi.org/10.3390/dermatopathology11040039 (registering DOI) - 12 Dec 2024
Viewed by 307
Abstract
PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. Immunohistochemistry (IHC) for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been [...] Read more.
PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. Immunohistochemistry (IHC) for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in supporting the differentiation between sebaceous and non-sebaceous lesions. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. This is a single-center retrospective cohort analysis over a ten-year period (1 January 2012, and 31 December 2023). We used the pathological database of skin lesions, including sebaceous, sweat gland, and follicular lesions, in addition to basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), from 81 patients who underwent shave/punch biopsies or surgical excisions. We evaluated the IHC staining percentage positivity and intensity for PRAME. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity was subcategorized into 0%, 1–25%, 26–50%, 51–75%, and 76–100%. Most sebaceous versus non-sebaceous lesions exhibited cytoplasmic staining of moderate to strong intensity in >75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, to support distinguishing between sebaceous and non-sebaceous adnexal lesions (regardless of whether they are benign or malignant). BCCs and SCCs showed weak to moderate nuclear staining for PRAME in >75% of cells. None of the 13 lesions of hair follicle origin showed any staining. A total of 26 of the 32 lesions of sweat gland origin were negative while 6 (18.75%) showed positive staining. In conclusion, we confirm the potential utility of PRAME for supporting the distinction between sebaceous and non-sebaceous adnexal lesions on one hand, and on the other, distinguishing BCC and SCC that may show nuclear staining from sebaceous carcinoma that shows cytoplasmic staining. Full article
(This article belongs to the Section Molecular Dermatopathology)
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<p>PRAME IHC staining in sebaceous lesions. The images show examples of benign and malignant sebaceous lesions which stained positively with PRAME (cytoplasmic staining).</p>
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<p>PRAME IHC staining in follicular lesions. The images show examples of follicular lesions which did not stain with PRAME.</p>
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<p>PRAME IHC staining in sweat gland lesions. The images show examples of sweat gland lesions which did not stain with PRAME.</p>
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<p>PRAME IHC staining in SCC and BCC. In the upper panel (squamous cell carcinoma), the neoplastic cells demonstrated weak nuclear staining for PRAME while the internal control sebaceous glands stained strongly positive for PRAME (cytoplasmic staining pattern). In the lower panel (basal cell carcinoma), the neoplastic cells demonstrated moderate nuclear staining for PRAME in &gt;75% of cells.</p>
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14 pages, 686 KiB  
Review
Genetic and Functional Changes in Mitochondria in the Pituitary Adenoma: The Pathogenesis and Its Therapy
by Hansen Wu, Jie Xu, Wenxuan Zhao, Weiqiang Lv, Zhihui Feng and Lijun Heng
Antioxidants 2024, 13(12), 1514; https://doi.org/10.3390/antiox13121514 - 11 Dec 2024
Viewed by 386
Abstract
Pituitary adenoma is a common neoplasm of the pituitary gland. Although most pituitary adenomas are benign, they can pose significant challenges in terms of their consequences and prognosis due to their tendency to invade surrounding tissues and their effects on hormone secretion. The [...] Read more.
Pituitary adenoma is a common neoplasm of the pituitary gland. Although most pituitary adenomas are benign, they can pose significant challenges in terms of their consequences and prognosis due to their tendency to invade surrounding tissues and their effects on hormone secretion. The management of pituitary adenomas typically involves surgery, medical therapy, and radiotherapy, each of which has its own limitations. Mitochondria play a crucial role in tumor development and progression by regulating various metabolic processes and signaling pathways within tumor cells and the tumor microenvironment. Multiple studies have indicated that mitochondrial dysfunction is implicated in human pituitary adenomas. Furthermore, several compounds with therapeutic effects on pituitary adenomas have been reported to target mitochondrial function. In this review, we summarize recent studies that highlight the involvement of mitochondrial homeostasis imbalance in the biology of pituitary adenomas. We conclude that mitochondria may represent a promising therapeutic target for the treatment of pituitary adenomas. Full article
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<p>Schematic representation of mitochondrial dysfunction and intervention in pituitary adenomas. Succinate dehydrogenase (<span class="html-italic">SDH</span>) mutations disrupt the tricarboxylic acid (TCA) cycle and increase reactive oxygen species (ROS) levels, potentially driving the development of pituitary adenomas. Additional pathogenic mechanisms include apoptotic protease activating factor-1 (APAF-1) downregulation, glutathione peroxidase 4 (GPX4) inhibition, and enhanced apoptosis. Certain natural compounds, such as 18β-glycyrrhetinic acid, curcumin, and grifolic acid, may inhibit ROS production and promote adenosine triphosphate (ATP) synthesis, thereby reducing tumor cell growth and showing potential therapeutic effects against pituitary adenomas.</p>
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12 pages, 499 KiB  
Article
Predictive Factors of Athyroglobulinemia After Total Thyroidectomy for Papillary Thyroid Cancer
by Marta Fernández-Baeza, Nuria V. Muñoz-Pérez, Ignacio Roldán-Ortiz, María J. Alonso-Sebastián, Francisco M. Carbajo-Barbosa, Rafael Rejón-López, María C. Olvera-Porcel, Antonio Becerra-Massare, Juan I. Arcelus-Martínez and Jesús María Villar-del-Moral
Cancers 2024, 16(24), 4129; https://doi.org/10.3390/cancers16244129 - 11 Dec 2024
Viewed by 356
Abstract
Background: Thyroglobulin (Tg) is the specific tumor marker for epithelial thyroid cancer. It holds significant value in the postoperative period, and somehow, the goal of surgery in papillary thyroid cancer (PTC) undergoing total thyroidectomy is to achieve undetectable levels of postoperative thyroglobulin [...] Read more.
Background: Thyroglobulin (Tg) is the specific tumor marker for epithelial thyroid cancer. It holds significant value in the postoperative period, and somehow, the goal of surgery in papillary thyroid cancer (PTC) undergoing total thyroidectomy is to achieve undetectable levels of postoperative thyroglobulin (uTg). Methods: This is a retrospective single-center study in which first basal Tg values were evaluated post-surgery in PTC patients undergoing total thyroidectomy. Patients with elevated antithyroglobulin antibodies were excluded. The impact of various demographic, clinical, therapeutic, tumor-stage related, and histopathological variables on the achievement of undetectable thyroglobulin levels (uTg, <1 ng/mL) was studied. A descriptive and logistic regression-based bivariate and multivariate analysis was planned using STATA vs. 16.1. program. The significance level was stated at 0.05. Results: Basal athyroglobulinemia was obtained in 89.6% of 202 patients operated on between January 2015 and June 2023 in a single referral institution. Due to the limited number of cases with detectable Tg, multivariate analysis could not be performed. The main factors that favored its achievement on bivariate analysis were a smaller tumor size (p = 0.003), no need for extended resections due to local invasion beyond the thyroid gland (p = 0.003) or neck dissection (p = 0.039), absence of distant metastases (p = 0.000), and a lower MACIS score (p < 0.000). Conclusions: The achievement of uTg was closely related to factors related to tumor stage (tumor diameter, lymph node spread, and metastatic disease), and it was not influenced by differences in epidemiological data, clinic manifestations, preoperative diagnosis, multifocality, or the presence of aggressive cytological variants. Full article
(This article belongs to the Special Issue New Insights into Thyroid Cancer Surgery)
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<p>Study flow chart. Tg: thyroglobulin. TgAb: antithyroglobulin antibodies. uTg: indetectable thyroglobulin.</p>
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14 pages, 1342 KiB  
Article
Common Bed Bugs: Non-Viable Hosts for Trypanosoma rangeli Parasites
by Sanam Meraj, Phillip Phung, Kelvin Lau, Carl Lowenberger and Gerhard Gries
Cells 2024, 13(24), 2042; https://doi.org/10.3390/cells13242042 - 11 Dec 2024
Viewed by 364
Abstract
The hemoflagellate parasite Trypanosoma rangeli is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener T. cruzi. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (i) the temporal and spatial [...] Read more.
The hemoflagellate parasite Trypanosoma rangeli is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener T. cruzi. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (i) the temporal and spatial distribution of T. rangeli in common bed bugs, Cimex lectularius, following oral ingestion and hemocoelic injection of T. rangeli, and (ii) the immune responses of bed bugs induced by T. rangeli infections. Irrespective of infection mode, no live T. rangeli were present in the bed bugs’ hemolymph, salivary glands, or feces. On day 1 following infection, the bed bugs strongly upregulated the antimicrobial peptide CL-defensin. Following hemocoelic injection of T. rangeli, live parasites were absent in any bed bug tissues examined throughout the 10-day study period. The ingestion of T. rangeli-infected blood had no significant effect on bed bug survival. Our findings indicate that bed bugs disable the development of T. rangeli within their body, in stark contrast to triatomine kissing bugs, which allow the development and transmission of T. rangeli. Our findings help unravel the intricate relationships between bed bugs and trypanosomes, and they contribute to our understanding of vector biology. Full article
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<p>Life stages of <span class="html-italic">Trypanosoma rangeli</span> found in the anterior midgut of the common bed bug, <span class="html-italic">Cimex lectularius</span>: Epimastigotes (<b>A</b>); intermediate forms (<b>B</b>,<b>C</b>). Cells were stained with Giemsa and visualized using oil emersion on a compound light microscope (×1000 magnification; scale: 10 μm).</p>
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<p>Results of the zone of inhibition (ZOI) test (three to five replicates) run to measure antibacterial (AB) activity expressed in midgut extracts of adult male bed bugs 0–10 days after an immune challenge. AB activity was tested against the bacterium <span class="html-italic">Bacillus subtilis</span> (10<sup>7</sup> cells/mL) and quantified as the zone of inhibited bacterial growth around a piece of filter paper treated with midgut protein extracts from bed bugs that had ingested sterile blood (control) or blood containing the parasite <span class="html-italic">Trypanosoma rangeli.</span> Bars represent the mean zone of inhibition ± 95% confidence intervals. Means were compared using the unpaired Student’s <span class="html-italic">t</span>-test. Different letters on bars indicate significant differences.</p>
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<p>Time-dependent expression of CL-defensin mRNA (LOC106661793) and CL-prolixicin mRNA (LOC106664366) in bed bugs after <span class="html-italic">Trypanosoma rangeli</span> ingestion. Expression levels of both antimicrobial peptide genes were quantified using the 2<sup>−ΔΔC(T)</sup> method [<a href="#B45-cells-13-02042" class="html-bibr">45</a>,<a href="#B46-cells-13-02042" class="html-bibr">46</a>]. Bars represent the mean transcript levels ± 95% confidence intervals. Means were compared using the unpaired Student’s <span class="html-italic">t</span>-test (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Kaplan–Meier plots depicting the survival of bed bugs that were starving (green line), had ingested sterile blood (black line), or had ingested blood infected with either the parasite <span class="html-italic">Trypanosoma rangeli</span> (purple line) or the bacterium <span class="html-italic">Escherichia coli</span> (red line). Lines marked with different letters are statistically different (<span class="html-italic">p</span> &lt; 0.05). Note: Bed bugs that ingested sterile blood or blood infected with <span class="html-italic">T. rangeli</span> had the same probability of survival.</p>
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