Exploring chromone-2-carboxamide derivatives for triple-negative breast cancer targeting EGFR, FGFR3, and VEGF pathways: Design, synthesis, and preclinical insights.

Chromone-based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone-2-carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA-MB-231, the triple-negative breast cancer cell line, was found to be the most sensitive, where the N-(2-furylmethylene) (15) and the α-methylated N-benzyl (17) derivatives demonstrated the highest growth inhibition with GI50 values of 14.8 and 17.1 µM, respectively. In vitro mechanistic studies confirmed the significant roles of compounds 15 and 17 in the induction of apoptosis and suppression of EGFR, FGFR3, and VEGF protein levels in MDA-MB-231 cancer cells. Moreover, compound 15 exerted cell cycle arrest at both the G0-G1 and G2-M phases. The in vivo efficacy of compound 15 as an antitumor agent was further investigated in female mice bearing Solid Ehrlich Carcinoma. Notably, administration of compound 15 resulted in a marked decrease in both tumor weight and volume, accompanied by improvements in biochemical, hematological, histological, and immunohistochemical parameters that verified the repression of both angiogenesis and inflammation as additional Anticancer mechanisms. Moreover, the binding interactions of compounds 15 and 17 within the binding sites of all three target receptors (EGFR, FGFR3, and VEGF) were clearly illustrated using molecular docking.

Comparative study between efficacy of Excimer light with topical Tacrolimus 0.1% versus excimer light with topical Bimatoprost 0.01% in treatment of facial Vitiligo.

Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus.

Rationale design of novel substituted 1,3,5-triazine candidates as dual IDH1(R132H)/ IDH2(R140Q) inhibitors with high selectivity against acute myeloid leukemia: In vitro and in vivo preclinical investigations.

In this study, novel substituted 1,3,5-triazine candidates (4a-d, 5a-j, and 6a-d) were designed as second-generation small molecules to act as dual IDH1 and IDH2 inhibitors according to the pharmacophoric features of both vorasidenib and enasidenib. Compounds 6a and 6b for leukemia cell lines showed from low to sub-micromolar GI50. Moreover, compounds 4c, 5f, and 6b described the frontier antitumor activity against THP1 and Kasumi Leukemia cancer cells with IC50 values of (10 and 12), (10.5 and 7), and (6.2 and 5.9) µg/mL, which were superior to those of cisplatin (25 and 28) µg/mL, respectively. Interestingly, compounds 4c, 6b, and 6d represented the best dual IDH1(R132H)/IDH2(R140Q) inhibitory potentials with IC50 values of (0.72 and 1.22), (0.12 and 0.93), and (0.50 and 1.28) µg/mL, respectively, compared to vorasidenib (0.02 and 0.08) µg/mL and enasidenib (0.33 and 1.80) µg/mL. Furthermore, the most active candidate (6b) has very promising inhibitory potentials towards HIF-1α, VEGF, and SDH, besides, a marked increase of ROS was observed as well. Besides, compound 6b induced the upregulation of P53, BAX, Caspases 3, 6, 8, and 9 proteins by 3.70, 1.99, 2.06, 1.73, 1.75, and 1.85-fold changes, respectively, and the downregulation for the BCL-2 protein by 0.55-fold change compared to the control. Besides, the in vivo behavior of compound 6b as an antitumor agent was evaluated in female mice bearing solid Ehrlich carcinoma tumors. Notably, compound 6b administration resulted in a prominent decrease in the weight and volume of the tumors, accompanied by improvements in biochemical, hematological, and histological parameters.

UPLC-qTOF-MS phytochemical profile of Commiphora gileadensis leaf extract via integrated ultrasonic-microwave-assisted technique and synthesis of silver nanoparticles for enhanced antibacterial properties.

The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 µg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 µg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.

Mathematical modeling of heat transfer in tissues with skin tumor during thermotherapy.

The study of thermal therapy to tumors and the response of living cells to this therapy used to treat tumor is very important due to the complexity of heat transfer in biological tissues. In the past few years, there has been a growing interest among clinicians, mathematicians, and engineers regarding the use of computational and mathematical methods to simulate biological systems. Numerous medical proceedings also employ mathematical modeling and engineering techniques as a means to guarantee their safety and evaluate the associated risks effectively. This manuscript provides an analytical solution used for the first time to study the mechanism of biological thermal response during heat therapy on spheroidal skin tumor. The proposed method used a generalized thermoelasticity model with one relaxation time. The influence of relaxation times on the responses of diseased and healthy tissues is studied and interpreted graphically. Also, the impact of different laser irradiance on the thermal profile of the malignant tumor cells over a period of 2 minutes is interpreted graphically. To investigate the transfer of heat within biological tissues during the thermal therapy, the Laplace transform and inverse Laplace transform methods were applied. A comparison of the present generalized thermoelasticity model and different models based on Pennes bioheat transfer PBT shows that our proposed model yields more realistic and accurate predictions. The current model can be used to explain various therapeutic methods.

Phytochemicals, Antioxidant, and Antidiabetic Effects of Ranunculus hirtellus Aerial Parts and Roots: Methanol and Aqueous Extracts.

Ranunculus hirtellus, also known as crowfoot (buttercup), has a rich tradition of use in various biological contexts. While antibacterial studies on extracts from this plant have been conducted, the phytochemical composition, antioxidant properties, and antidiabetic effects remain unexplored. In this study, the phytochemical, antioxidant, and antidiabetic effects of its methanol and aqueous extracts were investigated. Our approach involved gas chromatography-mass spectrometry (GC/MS), alongside quantitative and qualitative methods, for phytochemical profiles. Additionally, concerning biological activities, the antioxidant effect was assessed through 2, 2-diphenyl-pieryl hydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays, while the antidiabetic effect was examined through the α-amylase inhibitory assay. The chloroform, ethyl acetate, and n-hexane extracts of R. hirtellus revealed the presence of 14 distinct compounds. In the methanol extract, sterols, quinones, glycosides, lactones, lignin, and flavonoids were identified. The aqueous extract contained sterols, alkaloids, glycosides, triterpenes, terpenoids, quinones, leucoanthocyanins, and lactones. The total flavonoid content (TFC), total phenolic content (TPC), total tannin content (TTC), and reducing sugar content (RDC) were determined in plant extracts, and a linear relationship was found between these parameters. Additionally, the TTC, TPC, and TFC values for both extracts hovered around 0.3786, 0.0476, and 0.1864 µg/mL, respectively, across all plant concentrations, while RDC ranged from 0.9336 to 1.0119 µg/mL in all four extracts. In vitro assays demonstrated dose-dependent antidiabetic activity in both methanolic and aqueous extracts by inhibiting α-amylase. Furthermore, the antioxidant activity observed in the DPPH assay was greater in the aqueous extract compared with the methanolic extract. In addition, the ethyl acetate extract exhibited the highest inhibition among chloroform and n-hexane in the ABTS assay. The results suggest that R. hirtellus can be a potential source of natural antioxidants and antidiabetic agents, and further studies are warranted to investigate the underlying mechanisms of its therapeutic effects.

Thorough examination of the potential biological implications of the cuproptosis-related gene LIPT2 in the prognosis and immunotherapy in pan-cancer.

OBJECTIVES: To elucidate the expression levels and prognostic value of the Lipoyltransferase 2 (LIPT2) gene in a pan-cancer view. METHODOLOGY: Our study comprehensively investigated the role of LIPT2 in pan-cancer, combining bioinformatics analyses with experimental validations. RESULTS: Analysis of LIPT2 mRNA expression across various cancers revealed a significant up-regulation in 18 tumor types and down-regulation in 8 types, indicating its diverse involvement. Prognostic assessment demonstrated a correlation between elevated LIPT2 expression and poorer outcomes in Overall Survival (OS) and Disease-Free Survival (DFS), particularly in Glioblastoma Multiforme (GBM), Liver Hepatocellular Carcinoma (LIHC), and Pheochromocytoma and Paraganglioma (PCPG). Protein expression analysis in GBM, LIHC, and PCPG affirmed a consistent increase in LIPT2 levels compared to normal tissues. Examining the methylation status in GBM, LIHC, and PCPG, we found reduced promoter methylation levels in tumor samples, suggesting a potential influence on LIPT2 function. Genetic mutation analysis using cBioPortal indicated a low mutation frequency (< 2%) in LIPT2 across GBM, LIHC, and PCPG. Immune correlation analysis unveiled a positive association between LIPT2 expression and infiltration levels of immune cells in GBM, LIHC, and PCPG. Single-cell analysis illustrated LIPT2's positive correlation with functional states, including angiogenesis and inflammation. Enrichment analysis identified LIPT2-associated processes and pathways, providing insights into its potential molecular mechanisms. Drug sensitivity analysis demonstrated that elevated LIPT2 expression conferred resistance to multiple compounds, while lower expression increased sensitivity. Finally, RT-qPCR validation in HCC cell lines confirmed the heightened expression of LIPT2 compared to a control cell line, reinforcing the bioinformatics findings. CONCLUSION: Overall, our study highlights LIPT2 as a versatile player in cancer, influencing diverse aspects from molecular processes to clinical outcomes across different cancer types.

Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.

OBJECTIVES: In this comprehensive study spanning 33 malignancies, we explored the differential expression and prognostic significance of Heparan sulfate 6-O-sulfotransferase 2 (HS6ST2). METHODS: TIMER2, UALCAN, and GEPIA2 were used for the expression analysis. cBioPortal was used for mutational analysis. CancerSEA, STRING, and DAVID, were employed for the single cell sequencing data analysis, protein-protein interaction network development, and gene enrichment analyses, respectively. GSCAlite and RT-qPCR were used for drug sensitivity and expression validation analysis. RESULTS: HS6ST2 exhibited significant (P < 0.05) overexpression in multiple cancers. Prognostically, elevated HS6ST2 expression was significantly associated with poor overall survival (OS) in patients with cervical squamous cell carcinoma (CESC), kidney chromophobe (KICH), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD), emphasizing its potential as a prognostic indicator in these cancers. Moreover, HS6ST2 expression correlated with pathological stages in CESC, KICH, LUAD, and STAD patients. Exploration of genetic alterations using cBioPortal unveiled distinct mutational landscapes, with low mutation frequencies in CESC, KICH, LUAD, and STAD. Additionally, reduced DNA methylation in CESC, KICH, LUAD, and STAD suggested a potential link between hypomethylation and heightened HS6ST2 expression. Analysis of immune cell infiltration revealed a positive correlation between HS6ST2 expression and the infiltration of CD8+ T and CD4+ T cells in CESC, KICH, LUAD, and STAD, highlighting its involvement in the tumor immunology processes. Single-cell functional states analysis demonstrated associations between HS6ST2 and diverse cellular processes. Moreover, gene enrichment analysis revealed the involvement HS6ST2 in crucial cellular activities. GSCAlite analysis underscored the potential of HS6ST2 as a therapeutic target, showing associations with drug sensitivity. Finally, experimental validation through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in LUAD tissues confirmed elevated HS6ST2 expression. CONCLUSION: Overall, this study provides a comprehensive understanding of HS6ST2 in CESC, KICH, LUAD, and STAD, emphasizing its potential as a prognostic biomarker and therapeutic target.

Decoding the DSCC1 gene as a pan-cancer biomarker in human cancers via comprehensive multi-omics analyses.

OBJECTIVES: While dysregulation of DSCC1 (DNA Replication And Sister Chromatid Cohesion 1) has been established in breast cancer and colorectal cancer, its associations with other tumors remain unclear. Therefore, this study was launched to explore the role of DSCC1 in pan-cancer. METHODOLOGY: In this study, we investigate the biological functions of DSCC1 across 33 solid tumors, elucidating its role in promoting oncogenesis and progression in various cancers through comprehensive analysis of multi-omics data. RESULTS: We conducted a comprehensive analysis of DSCC1 expression using RNA-seq data from TCGA and GTEx databases across 30 cancer types. Striking variations were observed, with significant overexpression of DSCC1 identified in numerous cancers. Elevated DSCC1 level was strongly associated with poorer prognosis, shorter survival, and advanced tumor stages in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), as indicated by Kaplan-Meier curves and GEPIA2 analysis. Further investigation into the molecular mechanisms revealed reduced DNA methylation in the DSCC1 promoter region in KIRP, LIHC, and LUAD, supporting enhanced RNA transcription. Protein expression analysis via the Human Protein Atlas (HPA) corroborated mRNA expression findings, showcasing elevated DSCC1 protein in KIRP, LIHC, and LUAD tissues. Mutational analysis using cBioPortal revealed alterations in 0.4% of KIRP, 17% of LIHC, and 5% of LUAD samples, predominantly characterized by amplification. Immune cell infiltration analysis demonstrated robust positive correlations between DSCC1 expression and CD8+ T cells, CD4+ T cells, and B cells, influencing the tumor microenvironment. STRING and gene enrichment analyses unveiled DSCC1's involvement in critical pathways, emphasizing its multifaceted impact. Notably, drug sensitivity analysis highlighted a significant correlation between DSCC1 mRNA expression and responses to 78 anticancer treatments, suggesting its potential as a predictive biomarker and therapeutic target for KIRP, LIHC, and LUAD. Finally, immunohistochemistry staining of clinical samples validated computational results, confirming elevated DSCC1 protein expression. CONCLUSION: Overall, this study provides comprehensive insights into the pivotal role of DSCC1 in KIRP, LIHC, and LUAD initiation, progression, and therapeutic responsiveness, laying the foundation for further investigations and personalized treatment strategies.

Repurposing the drug, amprolium as a novel molluscicide against the land snail (Eobania vermiculata).

Amprolium (AMP) is an organic compound used as a poultry anticoccidiostat. The aim of this work is to repurpose AMP to control the land snail, Eobania vermiculata in the laboratory and in the field. When snails treated with ½ LC50 of AMP, the levels of alkaline phosphatase (ALP), total lipids (TL), urea, creatinine, malondialdehyde (MDA), catalase (CAT), and nitric oxide (NO) were significantly increased, whereas the levels of acetylcholinesterase (AChE), total protein (TP), and glutathione (GSH) decreased. It also induced histopathological and ultrastructural changes in the digestive gland, hermaphrodite gland, kidney, mucus gland, and cerebral ganglion. Furthermore, scanning electron micrographs revealed various damages in the tegumental structures of the mantle-foot region of E. vermiculata snails. The field application demonstrated that the AMP spray caused reduced percentages in snail population of 75 and 84% after 7 and 14 days of treatment. In conclusion, because AMP disrupts the biology and physiology of the land snail, E. vermiculata, it can be used as an effective molluscicide.

Intralesional injection of tuberculin purified protein derivative (PPD) versus measles, mumps, and rubella (MMR) vaccine in treatment of molluscum contagiosum: a comparative study.

Molluscum contagiosum (MC) is a skin and mucous membrane infection caused by the molluscum virus (MCV). To evaluate safety and efficacy of intralesional injection of tuberculin purified protein derivative (PPD) antigen injection versus MMR (mumps, measles, rubella) antigen for the treatment of molluscum contagiosum (MC). A total of thirty clinically confirmed patients of molluscum were recruited for this trial. Patients who were divided into three groups (A, B and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections, group (B) subjects received intralesional PPD injection and group (C) received intralesional saline injection. The results of the present study revealed complete clearance of the injected lesions in 12 patients (80%), partial response in 3 patients (20%) of group (A). In group (B), complete clearance of the treated warts was observed in 11 patients (73.3%) and partial response in 4 (26.7%) of patients. In group (C), the majority of patients 8 (53.3%) demonstrated no response while 7 (46.7%) patients showed only partial clearance. We established a good safety and efficacy profile for tuberculin PPD and MMR antigens in treatment of molluscum contagiosum.

Uncovering the Therapeutic Potential of Phosphocreatine in Diabetic Retinopathy: Mitigating Mitochondrial Dysfunction and Apoptosis via JAK2/STAT3 Signaling Pathway.

Diabetic retinopathy (DR) stands as a prevalent complication of diabetes mellitus, causing damage to the delicate retinal capillaries and potentially leading to visual impairment. While the exact underlying cause of DR remains elusive, compelling research suggests that mitochondrial energy deficiency and the excessive generation of reactive oxygen species (ROS) play pivotal roles in its pathogenesis. Recognizing that controlling hyperglycemia alone fails to reverse the defects in retinal mitochondria induced by diabetes, current strategies seek to restore mitochondrial function as a means of safeguarding against DR. To address this pressing issue, a comprehensive study was undertaken to explore the potential of phosphocreatine (PCr) in bolstering mitochondrial bioenergetics and providing protection against DR via modulation of the JAK2/STAT3 signaling pathway. Employing rat mitochondria and RGC-5 cells, the investigation meticulously assessed the impact of PCr on ROS production, mitochondrial membrane potential, as well as the expression of crucial apoptotic and JAK2/STAT3 signaling pathway proteins, utilizing cutting-edge techniques such as high-resolution respirometry and western blotting. The remarkable outcomes revealed that PCr exerts a profound protective influence against DR by enhancing mitochondrial function and alleviating diabetes-associated symptoms and biochemical markers. Notably, PCr administration resulted in an upregulation of antiapoptotic proteins, concomitant with a downregulation of proapoptotic proteins and the JAK2/STAT3 signaling pathway. These significant findings firmly establish PCr as a potential therapeutic avenue for combating diabetic retinopathy. By augmenting mitochondrial function and exerting antiapoptotic effects via the JAK2/STAT3 signaling pathway, PCr demonstrates promising efficacy both in vivo and in vitro, particularly in counteracting the oxidative stress engendered by hyperglycemia. In summary, our study sheds light on the potential of PCr as an innovative therapeutic strategy for diabetic retinopathy. By bolstering mitochondrial function and exerting protective effects via the modulation of the JAK2/STAT3 signaling pathway, PCr holds immense promise in ameliorating the impact of DR in the face of oxidative stress induced by hyperglycemia.

Hair disorders associated with post-COVID-19 infection in females: a cross-sectional study.

BACKGROUND: Coronavirus disease (COVID-19) currently named SARS-CoV-2 is a contagious disease caused by a coronavirus. The virus may infect the hair follicles directly or indirectly through systemic changes in the immune or hormonal systems. AIMS: In the current study we aimed to determine the prevalence of hair disorders in females infected with COVID-19. METHODS: Data was collected using a questionnaire covering four main domains: personal data, past medical history, COVID-19 history and treatment, and existence of any hair problems and their management. No identifier or sensitive data were collected. Those complaining of hair loss were subjected to complete general and local hair examination using trichoscopy to confirm hair loss. RESULTS: Hair problems were reported in 307 (61.4%) of COVID-19-infected female subjects. A total of 68.1% patients reported that hair loss existed and increased after COVID-19; 29.6% reported their hair problems only post-COVID-19 while 2.3% had hair shedding issues during infection only. The main reported hair problems were telogen effluvium (60.8%), increased gray hair (13.8%), seborrheic dermatitis (5.6%) trichotillomania (3.6%), and alopecia areata (2.2%). CONCLUSION: In conclusion, we reported prevalence of post-COVID hair fall that was confirmed by trichoscopy and which affected approximately 61.4% of infected females.

A Review on the Efficacy of Plant-derived Bio-active Compounds Curcumin and Aged Garlic Extract in Modulating Cancer and Age-related Diseases.

Aging is a process characterized by accumulating degenerative changes resulting in the death of an organism. Aging is mediated by various pathways that are directly linked to the individual's lifespan and are shunted for many age-related diseases. Many strategies for alleviating age-related diseases have been studied, which can target cells and molecules. Modern drugs such as Metformin, Rapamycin, and other drugs are used to reduce the effects of age-related diseases. Despite their beneficial activity, they possess some side effects which can limit their applications, mainly in older adults. Natural phytochemicals which have anti-aging activities have been studied by many researchers from a broader aspect and suggested that plant-based compounds can be a possible, direct, and practical way to treat age-related diseases which has enormous anti-aging activity. Also, studies indicated that the synergistic action of phytochemicals might enhance the biological effect rather than the individual or summative effects of natural compounds. Curcumin has an antioxidant property and is an effective scavenger of reactive oxygen species. Curcumin also has a beneficial role in many age-related diseases like diabetes, cardiovascular disease, neurological disorder, and cancer. Aged garlic extracts are also another bioactive component that has high antioxidant properties. Many studies demonstrated aged garlic extract, which has high antioxidant properties, could play a significant role in anti-aging and age-related diseases. The synergistic effect of these compounds can decrease the requirement of doses of a single drug, thus reducing its side effects caused by increased concentration of the single drug.

Immune modulation and prognostic significance of MCM10 in pan-cancer: a comprehensive analysis.

BACKGROUND: Oncogenic processes in cancer are often characterized by dysregulation of critical genes. Our study focused on the minichromosome maintenance 10 replication initiation factor (MCM10) gene's expression and its potential diagnostic and prognostic implications in pan-cancer. METHOD: Leveraging large-scale genomic datasets, and experimental validation we embarked on a comprehensive analysis to shed light on the diagnostic and prognostic role of MCM10. RESULTS: Our findings underscore the wide-ranging up-regulation of MCM10 across 24 major cancer types, positioning it as a ubiquitous player in tumorigenesis. Significantly, MCM10 up-regulation was strongly associated with poorer overall survival in Kidney Renal Papillary Cell Carcinoma (KIRP), Liver Hepatocellular Carcinoma (LIHC), and Lung Adenocarcinoma (LUAD), emphasizing its potential as a valuable prognostic marker in these cancers. While genetic mutations often drive oncogenic processes, our mutational analysis revealed the relative stability of MCM10 in KIRP, LIHC, and LUAD. This suggests that epigenetic (hypomethylation) and non-mutational regulatory mechanisms predominantly govern MCM10 expression in these cancer types. Further analyses demonstrated positive correlations between MCM10 expression and immune cell infiltration, particularly CD8+ T cells and CD4+ T cells, offering insights into the gene's influence on the tumor immune microenvironment. Additionally, pathway enrichment analysis highlighted MCM10-associated genes' involvement in crucial signaling pathways, such as the cell cycle, DNA replication, and repair. Exploring the therapeutic potential, we examined important drugs capable of regulating MCM10 expression, opening doors to personalized treatment strategies. CONCLUSION: Our study elucidates the multifaceted roles of MCM10 in KIRP, LIHC, and LUAD. Its pervasive up-regulation, prognostic significance, epigenetic regulation, and influence on the immune microenvironment provide valuable insights into these cancers. This research contributes to the growing body of evidence surrounding MCM10 and invites further investigation, validation, and potential translational efforts to harness its clinical relevance.

Dynamic response of a long cylinder under thermal shock in micropolar thermoelasticity.

In this manuscript, the dynamic response of a long cylinder subjected to an asymmetric thermal shock is investigated within the framework of generalized micropolar thermoelasticity. The displacement and micro-rotation are assumed to vanish at the surface. Laplace transformation techniques are used to solve the problem. The solution is obtained in the transformed field using an innovative direct approach. Furthermore, we obtain the inverse transformations using a numerical method based on Fourier expansion. The obtained results are carefully presented through graphical representations and discussed extensively across different relaxation time values. It is evident that the relaxation time parameter significantly influences all the distributions. The displacement distributions are always continuous, whereas all other functions, including temperature variation, stress distribution, and micro-rotation, exhibit discontinuity at the wave front. The results obtained hold significant importance in various technological applications and in the manufacturing of mechanical components.

Evaluation of the Cutting Seton Technique in Treating High Anal Fistula.

Objectives Fistula-in-ano is a common condition that negatively affects the quality of life of its sufferers. A high anal fistula poses a significant challenge for surgeons due to its proximity to the anorectal ring and the potential risk of incontinence rather than recurrence. Many modalities have been used in a justified search for a satisfactory cure for the condition, but the seton remains a mainstay of surgical treatment. Therefore, the rationale of this study is to assess the outcome of treating a high anal fistula using the cutting seton technique in a hospital in Al Madinah, Saudi Arabia. The evaluation is intended through a retrospective analysis of patients' outcomes, comparing its effectiveness to similar articles. Methods This is a retrospective study that includes 50 patients with high anal fistulas who were treated with a cutting seton at the National Guard Hospital over a four-year period (2019-2022). Information obtained from medical records included clinical and demographic data. The data collected during the study was compiled and statistically analyzed using the SPSS Statistics version 26.0 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.). A p-value of <0.05 was considered statistically significant. Results A total of 50 patients with high anal fistula treated with a cutting seton were included: 82% were males and 18% were females, with 66% below 45 years of age. Approximately 92% had inter-sphincteric fistulas, and only 28% had a recurrent fistula. Almost all patients (98%) had an MRI done before surgery. Around 70% of patients were completely cured, 26% had minor complications, 8% of the operated patients experienced mild incontinence, and only one recurrence (2%). Conclusion The cutting seton is still a valid modality in treating patients with a high anal fistula, as it is considerably safe, effective, and yields good outcomes. Standard preoperative assessment and thorough surgical techniques are cornerstones for achieving a satisfactory outcome.

Anti-inflammatory and anti-oxidant activities of mesenchymal stem cells in chemically induced arthritic rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have been extensively used as cell-based treatments for decades due to their anti-inflammatory, immunomodulatory, and healing abilities. The intent of our study was to determine the efficacy of MSCs in alleviating rheumatoid arthritis (RA) induced by Complete Freund's adjuvant (CFA) and to investigate the anti-inflammatory and antioxidant characteristics of MSCs. METHODS AND RESULTS: Intrapedally injecting 0.1 ml of CFA directly into the footpad of the right hind paw daily for 2 days was used to induce RA. Arthritic rats received four doses of MSCs (1 × 106 cells/rat/dose) intravenously through the lateral tail vein. Our results showed that arthritic rats treated with MSCs exhibited reduced levels of paw edema. Furthermore, arthritic rats treated with MSCs exhibited a significant decrease in the levels of RF, CRP, IL-1ß, TNF-α, IL-17 and ADAMTS-5, along with a significant increase in the levels of IL-4 and TIMP-3. Additionally, MSCs significantly reduced the expression of TGF-ß. Both the glutathione (GSH) content and antioxidant activity of GST were enhanced by MSCs, while LPO levels were suppressed. CONCLUSION: These findings provide further evidence that MSCs are valuable in treating RA, possibly due to their anti-inflammatory and anti-oxidative properties. Thus, MSCs have potential as a more effective therapeutic strategy for treating RA.

A study on the therapeutic potential of graphene titanate nanocomposite for treating chemically induced arthritis in rats.

Nanotechnology holds substantial promise in the innovative therapies for rheumatoid arthritis (RA). The current study was designed to synthesize and characterize a new graphene titanate nanocomposite (GTNc) and explore its anti-arthritic, anti-inflammatory, and antioxidant potencies against Complete Freund's adjuvant (CFA)-induced arthritis in rats, as well as investigate the underlying molecular mechanisms. Our characterization methods included XRD, FT-IR, SEM, EDX, zeta potential, practical size, and XRF to characterize the novel GTNc. Our findings revealed that arthritic rats treated with GTNc exhibited lower levels of RF, CRP, IL-1ß, TNF-α, IL-17, and ADAMTS-5, and higher levels of IL-4 and TIMP-3. In arthritic rats, GTNc reduced LPO levels while increasing GSH content and GST antioxidant activity. Additionally, GTNc decreased the expression of the TGF-ß mRNA gene in arthritic rats. Histopathological investigation showed that GTNc reduced inflammatory cell infiltration, cartilage degradation, and bone destruction in joint injuries caused by CFA in the arthritic rats. Collectively, the anti-arthritic, anti-inflammatory, and antioxidant properties of GTNc appear promising for future arthritis treatments and bone disability research.

Unraveling the Anticancer Potential of Statins: Mechanisms and Clinical Significance.

Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression of cholesterol production, statins appear to have pleitropic effects in a wide variety of other diseases by modulating signaling pathways. In recent years, statins have seen a large increase in interest due to their putative anticancer effects. Statins appear to cause upregulation or inhibition in key pathways involved in cancer such as inhibition of proliferation, angiogenesis, and metastasis as well as reducing cancer stemness. Further, statins have been found to induce oxidative stress, cell cycle arrest, autophagy, and apoptosis of cancer cells. Interestingly, clinical studies have shown that statin use is associated with a decreased risk of cancer formation, lower cancer grade at diagnosis, reduction in the risk of local reoccurrence, and increasing survival in patients. Therefore, our objective in the present review is to summarize the findings of the publications on the underlying mechanisms of statins' anticancer effects and their clinical implications.