Search Results (4,943)

This study investigates the fabrication and characterization of polymeric nanoparticles based on polyhydroxyalkanoates (PHAs) loaded with curcumin for biomedical applications. PHAs, biodegradable and biocompatible polymers, were synthesized via bacterial fermentation and used to encapsulate curcumin using the nanoprecipitation method. The resulting nanoparticles were characterized for their particle size, polydispersity index, and encapsulation efficiency, achieving high entrapment rates (above 80%) and nanometric size distribution. Stability assessments demonstrated prolonged structural integrity under storage conditions. In vitro release studies conducted in phosphate-buffered saline at pH 5 and 7.4 revealed sustained drug release profiles. Biocompatibility and cytotoxicity assays using human astrocytes and fibroblasts confirmed the nanoparticles’ safety, while antiproliferative tests on glioblastoma and colon cancer cell lines indicated potential therapeutic efficacy. Additionally, skin irritation and corrosion tests using the EpiDerm™ model classified the formulations as non-irritant and non-corrosive. These findings suggest that PHA-based nanoparticles offer a promising nanocarrier system for curcumin delivery, with potential applications in cancer treatment and regenerative medicine. Future research should focus on optimizing the formulation and evaluating in vivo therapeutic effects. Full article

Non-small cell lung cancer (NSCLC) is a challenging disease, with the epidermal growth factor receptor (EGFR) being a key target for new, effective treatments crucial for the signaling pathways regulating cancer cell survival. Targeting EGFR-mediated signaling offers promising strategies to improve NSCLC therapies, particularly in overcoming resistance in EGFR-mutant lung cancer. In this study, we investigated the anticancer effects of panduratin A, a naturally occurring flavonoid from Boesenbergia rotunda, on human NSCLC cell lines expressing both wild-type EGFR (A549) and mutant EGFR (H1975) using in vitro experiments and molecular docking approaches. Cytotoxicity screening revealed that panduratin A exhibits potent effects on both A549 (IC₅₀ of 6.03 ± 0.21 µg/mL) and H1975 (IC₅₀ of 5.58 ± 0.15 µg/mL) cell lines while demonstrating low toxicity to normal MRC5 lung cells (12.96 ± 0.36 µg/mL). Furthermore, western blotting and flow cytometric analyses indicated that panduratin A induces apoptosis by inhibiting p-EGFR and its downstream effectors, p-STAT3 and p-Akt, in lung cancer cells. Additionally, the docking study showed lower binding energy between panduratin A and the target proteins, comparable to that of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). The ADMET prediction also highlighted panduratin A’s exceptional drug-like properties. This study concludes that panduratin A shows significant promise as an anti-lung cancer candidate for NSCLC, offering an economical and effective strategy. Full article

Cell-mediated immunity and chronic inflammation are hallmarks of chronic kidney disease (CKD). Growth differentiation factor 15 (GDF15) is a marker of inflammation and an integrative signal in stress conditions. Epidermal growth factor (EGF) is a tubule-specific protein that modulates the regeneration of injured renal tubules. Neopterin is a product of activated monocytes and macrophages and serves as a marker of cell-mediated immunity. Our aim was to assess the role of the above-mentioned parameters in the progression of CKD in children using artificial intelligence tools. The study group consisted of 151 children with CKD stages 1–5. EGF, GDF15, and neopterin serum concentrations were assessed by ELISA. The patients’ anthropometric data, biochemical parameters, EGF, GDF15, and neopterin serum values were implemented into the artificial neural network (ANN). The most precise model contained EGF, GDF15, and neopterin as input parameters and classified patients into either CKD 1–3 or CKD 4–5 groups with an excellent accuracy of 96.77%. The presented AI model, with serum concentrations of EGF, GDF15, and neopterin as input parameters, may serve as a useful predictor of CKD progression. It suggests the essential role of inflammatory processes in the renal function decline in the course of CKD in children. Full article

Background/Objectives: In 2022, approximately 2.3 million women were diagnosed with breast cancer worldwide, resulting in 670,000 deaths, which accounted for 6.9% of all cancer-related deaths. In the United States, 1 in 8 women will be diagnosed with breast cancer during their lifetime. It was estimated that 2024 would identify about 310,720 women and 2800 men diagnosed with invasive breast cancer. The future global burden of breast cancer is projected to rise to over 3 million new cases and 1 million deaths by 2040. Approximately 20% of breast cancer diagnoses are triple-negative breast cancer (TNBC), a type of cancer that lacks receptors for estrogen (ER-negative), progesterone (PR-negative), and human epidermal growth factor receptor 2 (HER2/neu-negative). Consequently, TNBC does not respond to hormonal or targeted therapies, making it challenging to treat due to its rapid growth, metastasis, and high recurrence rate within the first three years of therapy. Alternative chemotherapies are needed to address this problem. A pharmacological dose of vitamin C (high-dose VC) has been identified as a potential treatment for some cancer cells. The present study aimed to evaluate whether VC has a therapeutic effect on TNBC, using MDA-MB-231 cells as the model. Additionally, VC’s effects were trialed on other cancer cells such as MCF7 and on non-cancerous kidney HEK 293 and lung CCL205 cells. Methods: The MTT assay, Hoechst 33342 staining, nuclear-ID red/green staining, Rhodamine 123 staining, and Western blot analysis were employed to test the hypothesis that a pharmacological dose of VC can kill TNBC cells. Results: The upregulation of Apaf-1 and caspases -7, -8, and -9, the inhibition of matrix metalloproteinases (MMP-2 and MMP-9), a reduction in cell cycle protein expression, and the enhancement of tumor suppressor proteins such as p53 and p21 indicate that a pharmacological dose of VC has promising anti-cancer properties in the treatment of breast cancers. Conclusions: Pharmacological dose of VC exerts significant anti-cancer effects in MDA-MB-231 cells by promoting apoptosis, inhibiting metastasis, disrupting cell cycle progression, and enhancing tumor suppressor activity. Full article

Background: Lung cancer is the leading cause of cancer-related deaths globally, with epidermal growth factor receptor (EGFR) mutations present in approximately 17–39% of non-small cell lung cancer (NSCLC) cases. Osimertinib, a third-generation oral EGFR tyrosine kinase inhibitor (EGFR-TKI), has become a cornerstone in the treatment of EGFR-mutated NSCLC. However, the full scope of its potentially life-threatening adverse effects, particularly cardiomyopathy, remains underexplored. Methods: This retrospective study was conducted using data from a multi-center registry of NSCLC patients with EGFR mutations treated with first-line osimertinib therapy between December 2018 and April 2024. Osimertinib-related cardiotoxicity was defined as a composite of reduced ejection fraction (EF) and cardiac death. Results: The study cohort consisted of 17 patients, and most of the patients had a history of smoking. Cardiac toxicity onset varied from 1 to 28 months following osimertinib initiation, with 70.59% of the patients experiencing symptoms within the first 6 months of treatment. Fourteen patients showed some degree of symptom improvement and EF recovery, although most did not return to baseline EF levels. Comorbidities, including heart failure, hypertension, and dyslipidemia, were prevalent across the cohort. Conclusions: While osimertinib remains an effective treatment for EGFR-mutated NSCLC, its associated cardiac toxicity, particularly in patients with pre-existing conditions, presents a significant challenge. Close monitoring, early intervention, and individualized management strategies are critical in mitigating these risks. Patients with mild cardiac toxicity may be suitable for rechallenge, while those with more severe or persistent toxicity should generally be excluded from further osimertinib treatment. Full article

Scaled integument of six species of the genus Acanthocercus and Laudakia nupta, family Agamidae was studied using light and scanning electron microscopy. Gross observation revealed the presence of two types of modified scales in the males. The enlarged scales covered with an extremely thick β-corneous layer were detected in the dorsal and ventral surfaces of the tail base and on the palmar and plantar limb surfaces of all species. After detachment of the β-layer, the surface of such scales was covered with high papillae (“papillary scales”). The callous scales were found in the precloacal region of Acanthocercus species and in both precloacal and mid-ventral regions of L. nupta. Modified scales were found in some females and subadut specimens, and absent in juveniles. A prominent papillary layer characterized the dermis of both scale types. It was assumed that well-developed dermal papillae in such scales expended the total surface area of stratum germinativum and created a pool of proliferated cells in the interpapillary loops to increase the production of differentiating keratinocytes. These processes were undoubtedly associated with the formation of a thick and resistant corneous layer that distinguished both types of scales. Functional role, a taxonomic value, and analogies with normal and pathological epidermis in birds and mammals are discussed. Full article

The novel plant hormone strigolactones (SL) are involved significantly in plant growth and development. Its key members SMXL6, 7, 8 can modulate SL signal reception and response negatively and can regulate plant branching remarkably. There are relatively scarce studies of cotton SMXL gene family, and this study was carried out to clarify the role of GbSMXL8 in cotton fiber development. Phylogenetic analysis identified 48 cotton SMXL genes, which were divided into SMXL-I (SMXL 1, 2), SMXL-II (SMXL 3) and SMXL-III (SMXL6, 7, 8) groups. The results of the cis-element analysis indicated that the SMXL gene could respond to hormones and the environment to modulate cotton growth process. A candidate gene GbSMXL8 was screened out based on the expression difference in extreme varieties of Gossypium barbadense. Tissue-specific analysis indicated that GbSMXL8 was mainly expressed in roots, 20D, 25D, and 35D and was involved in SL signaling pathways. In vitro ovule culture experiments showed that exogenous SLs (GR24) could promote the fiber elongation of G. barbadense, and GbSMXL8 expression was increased after GR24 treatment, indicating that GbSMXL8 was specifically responsive to GR24 in regulating fiber growth. GbSMXL8 knockout resulted in creased length and number of epidermal hairs and the length of fiber, indicating the interference role of GbSMXL8 gene with the development of cotton fiber. The GbSMXL8 transgenic plant was detected with a higher chlorophyll content and photosynthetic rate than those of the control plant, producing a direct impact on plant growth, yield, and biomass accumulation. GbSMXL8 gene knockout could increase plant height, accelerate growth rate, and lengthen fiber length. Intervening GbSMXL8 may mediate cotton growth, plant type formation and fiber elongation. In conclusion, the present study uncovers the function of GbSMXL8-mediated SL signal in cotton, providing theoretical insight for future breeding of new cotton varieties. Full article

Background: Dermatological emergencies are critical conditions requiring immediate attention due to their potential to escalate into life-threatening scenarios. Accurate diagnosis and timely management are essential to prevent severe complications, including systemic involvement and mortality. This systematic review summarizes findings on dermatological emergencies in emergency departments (EDs), focusing on diagnostic accuracy, hospitalization rates, systemic complications, and management strategies. Methods: A systematic literature review of studies on dermatological emergencies was conducted, encompassing 24 prospective and retrospective cohort studies, cross-sectional studies, and descriptive analyses. The review included diverse patient populations, examining dermatological presentations, diagnostic methods, treatment strategies, hospitalization rates, and adverse outcomes. Key outcome measures such as diagnostic accuracy, complications, mortality rates, and re-visit frequencies were analyzed. Results: The studies revealed high diagnostic accuracy, particularly in in-person evaluations, with teledermatology showing slightly lower but reliable rates. Systemic complications, including severe drug reactions, bacterial infections, and autoimmune diseases, were common causes of hospitalization. Mortality rates varied, with conditions such as toxic epidermal necrolysis showing the highest risk. Hospitalization rates averaged 4.52%, and re-visit rates ranged from 1% to 6.5%. The results also highlighted the impact of environmental factors and seasonal trends on dermatological presentations. Conclusions: Dermatological emergencies pose significant challenges in emergency care. High diagnostic accuracy and effective management strategies are crucial in preventing severe outcomes. Timely diagnosis, careful management of systemic complications, and teledermatology play critical roles in improving care. Future research should focus on standardized management protocols, telemedicine applications, and the influence of environmental and demographic factors to enhance patient outcomes. Full article

Background: HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing evidence for optimizing treatment strategies. Methods: NSCLC patients diagnosed at Jiangsu Province People’s Hospital from 2016 to 2024 were enrolled. HER2-positive cases were screened by IHC/FISH and further profiled by NGS. Treatment response was assessed by RECIST 1.1, and survival analysis was performed using Kaplan–Meier and log-rank tests. Results: Among 144 HER2-mutant NSCLC cases confirmed by NGS, 10 insertion mutations, 26 missense mutations, and 2 fusion mutations were identified. The most common mutation was the exon 20 p.A775_G776insYVMA (47.9%), and TP53 was the most frequent co-mutation (10.4%). In terms of efficacy, the pyrotinib-based combination therapy demonstrated significant clinical benefit, with an ORR of 33.3%, DCR of 95.2%, median PFS (mPFS) of 11.3 months (95% CI: 10.27–12.26), and median OS (mOS) of 21.0 months (95% CI: 18.00–23.94). Subgroup analysis revealed no significant impact of mutation subtype or co-mutation status on the treatment efficacy, but patients with brain metastases had a significantly worse prognosis than those without metastasis (mPFS: 5.1 vs. 12.9 months, p < 0.01; mOS: 9.3 vs. 26.5 months, p < 0.01). All TRAEs were grade 1–3 (any grade: 90.5%; grade 3: 14.3%), with the most common TRAE being diarrhea (any grade: 85.7%; grade 3: 9.5%). Conclusions: Pyrotinib-based combination therapy is a feasible first-line treatment for HER2-mutant NSCLC, demonstrating significant survival benefits and manageable toxicity. However, brain metastasis patients require enhanced comprehensive management. Full article

Aloe vera has garnered significant scientific and commercial attention due to its multifaceted therapeutic and cosmetic potential. This study aimed to investigate the biological effects and molecular mechanisms of Aloe vera phytoplacenta extract (AVPE) on HaCaT cells and skin health. To achieve this, we investigated AVPE, produced using advanced in vitro cell culture techniques, and its effects on HaCaT cells. At 2% concentration, AVPE demonstrated remarkable biological effects, increasing AQP3 protein expression by 120% and healing area fourfold while simultaneously reducing COX-2 messenger RNA (mRNA) by 43% and iNOS mRNA by 48%. An AVPE-containing product notably reduced facial skin temperature to 24.9 °C compared to 32.3 °C for the control product. RNA-sequencing (RNA-seq) analysis of transcriptional changes in HaCaT cells after AVPE treatment revealed 14 upregulated and 58 downregulated RNAs. Upregulated processes included response to hydrogen peroxide and muscle cell migration, while downregulated processes involved cell–cell adhesion and synaptic transmission. Pathway analysis further highlighted significant metabolic changes, including upregulation of pentose phosphate and galactose metabolism pathways and downregulation of the leishmaniasis and GABAergic synapse pathways. In addition, gene expression data indicated subtle changes in epidermal differentiation genes, modulation of inflammatory markers, and alterations in genes related to cell signaling and skin-specific functions. Our comprehensive findings underscore AVPE’s potential in enhancing skin healing, regulating temperature, and modulating cellular processes. Full article

Unwanted abdominal fat is a common aesthetic concern treated through various interventions, including surgical and energy-based devices, often leading to inconsistent results. This study aimed to evaluate the feasibility of a localized, non-invasive microwave (MW) device for preferential heating of subcutaneous adipose tissue using a controlled electromagnetic field. Five female volunteers scheduled for abdominoplasty were enrolled, each undergoing a single MW treatment session five days prior to surgery. Histological analyses of adipose tissue and skin samples were conducted using Hematoxylin and Eosin staining and immunohistochemistry for Perilipin-1 and CD68. Epidermal and dermal layers remained unaffected, as evidenced by unaltered morphology in treated samples. In contrast, the absence of Perilipin-1 expression in disrupted fat cell membranes indicated adipocyte non-viability and irreversible injury. Inflammatory responses, including CD68-positive macrophages surrounding damaged adipocytes, were observed, suggesting the activation of the monocyte/macrophage system for the clearance of adipocyte residues. Microscopic and immunohistochemical findings demonstrate the effectiveness of the MW device in reducing subcutaneous fat. This study also discussed the underlying mechanisms involved in macrophage recruitment and the removal of adipocyte residues. Full article

Mutations in the tumor suppressor genes BRCA1 and BRCA2 are associated with the triple-negative breast cancer phenotype, particularly aggressive and hard-to-treat tumors lacking estrogen, progesterone, and human epidermal growth factor receptor 2. This research aimed to understand the metabolic and genetic links behind BRCA1 and BRCA2 mutations and investigate their relationship with effective therapies. Using the Cytoscape software, two networks were generated through a bibliographic analysis of articles retrieved from the PubMed-NCBI database. We identified 98 genes deregulated by BRCA mutations, and 24 were modulated by therapies. In particular, BIRC5, SIRT1, MYC, EZH2, and CSN2 are influenced by BRCA1, while BCL2, BAX, and BRIP1 are influenced by BRCA2 mutation. Moreover, the study evaluated the efficacy of several promising therapies, targeting only BRCA1/BRCA2-mutated cells. In this context, CDDO-Imidazolide was shown to increase ROS levels and induce DNA damage. Similarly, resveratrol decreased the expression of the anti-apoptotic gene BIRC5 while it increased SIRT1 both in vitro and in vivo. Other specific drugs were found to induce apoptosis selectively in BRCA-mutated cells or block cell growth when the mutation occurs, i.e., 3-deazaneplanocin A, genistein or daidzein, and PARP inhibitors. Finally, over-representation analysis on the genes highlights ferroptosis and proteoglycan pathways as potential drug targets for more effective treatments. Full article

Background: The fragile X protein family comprises three members: the fragile X syndrome protein (FMRP) and its structural homologs, fragile X syndrome 1 and 2 (FXR1 and FXR2). FMRP has a significant role in controlling the genesis and progression of various forms of human cancer. However, studies on the prognostic significance of FXR2 in cancer are scarce. Thus, this study aimed to investigate the clinicopathological significance of FXR2, a member of the FMRP family, in primary breast cancer (BC). Methods: A total of 100 formalin-fixed paraffin-embedded (FFPE) tissue blocks from invasive BC cases were collected from King Abdulaziz Hospital in Saudi Arabia. Immunohistochemistry (IHC) was used to assess FXR2 protein expression in the BC tissues, and the results were correlated with clinicopathological parameters, such as tumor grade, tumor size and hormone receptor status. Additionally, the association between clinicopathological features and FXR2 mRNA expression was assessed using the BC Gene-Expression Miner v5.0 tool on all publicly available DNA microarray (n = 10,872) and RNA sequence (n = 4421) data to validate the results. Results: FXR2 protein expression was significantly associated with human epidermal growth factor 2 (HER2) negativity (p = 0.010) and low Ki67 (p < 0.001). Both DNA microarray and RNA sequence data showed that HER2 negativity was strongly linked to high levels of FXR2 mRNA. High FXR2 mRNA levels were also correlated with hormone receptor negativity and mutated p53. Conclusions: This study suggests that FXR2 may have indirect clinical significance in BC. However, further studies are warranted to deepen our understanding of the association between FXR2 and other clinicopathological parameters, which could lead to improved diagnostic, treatment, and prognostic strategies for BC patients. Full article

Background: The causal relationship between exposure to ultraviolet radiation and the development of skin cancers requires constant research for possible orchestrating mechanisms. In recent years, the Hippo pathway, along with its effector protein YAP, became implicated in cutaneous carcinogenesis; however, Hippo pathway regulation by ultraviolet radiation has not been described thoroughly. In order to address this issue, we focused on how different doses of ultraviolet B affect Hippo signaling pathway components and its upstream regulators, JNK1/2 and ABL1, in human keratinocytes. Additionally, we decided to determine how silencing of YAP influences Hippo pathway component expression. Methods: Primary epidermal keratinocytes were irradiated using UVB lamps with increasing doses of ultraviolet B radiation (including 311 nm UVB). Real-time PCR was used to determine the mRNA levels of each investigated gene. The experiment was then performed after YAP silencing using siRNA transfection. Additionally, we determined the mRNA expression of Hippo pathway components in an A431 cSCC cell line. Results: We observed that YAP mRNA expression in the A431 cell line was insignificant in comparison to control, while in the case of LATS1/2, a significant increase was noted. UVB irradiation did not change the levels of YAP mRNA expression in human epidermal keratinocytes. LATS1, LATS2, ABL1 and MAP4K4 mRNA expression was significantly upregulated after UVB irradiation in non-YAP-silenced keratinocytes in a dose-dependent manner, while after YAP silencing, only LATS2 and ABL1 showed significant mRNA upregulation. The 311 nm UVB irradiation resulted in significant, dose-dependent mRNA upregulation in non-YAP-silenced keratinocytes for LATS1, ABL1 and MAP4K4. After YAP silencing, a significant change in mRNA expression was present only in the case of ABL1. Conclusions: YAP mRNA expression does not significantly increase after exposure to UVB; however, it upregulates the expression of its proven (LATS1/2, JNK1/2) regulators, suggesting that in real-life settings, UV-induced dysregulation of the Hippo pathway may not be limited to YAP. Full article

Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-Skin^TM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits. Full article