搜索结果：Cellular and molecular biology (Noisy-le-Grand, France)

Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by dysregulated immune responses, epithelial barrier dysfunction, and progressive tissue damage. Despite advances in biologic therapies, treatment resistance and loss of response remain common. The activating receptor NKG2D, expressed on natural killer cells and T cell subsets, recognizes stress-induced ligands (MICA, MICB, ULBP) upregulated on intestinal epithelial cells under inflammatory conditions. In CD, sustained ligand expression promotes NKG2D-dependent cytotoxicity, pro-inflammatory cytokine release (IFN-γ, IL-17), and lymphocyte trafficking into the mucosa, perpetuating a cycle of epithelial injury and chronic inflammation. Preclinical colitis models and clinical trials with anti-NKG2D monoclonal antibodies (e.g., NNC0142-0002) demonstrate reduced disease activity, improved histological outcomes, and induction of remission in moderate-to-severe CD patients. However, challenges remain, including potential impairment of immune surveillance against infections and tumors, patient heterogeneity, and pathway redundancy. Future directions include biomarker-guided patient selection, combination therapies with anti-TNF or anti-integrin agents, and next-generation biologics such as bispecific antibodies. Understanding the cellular and molecular basis of NKG2D signaling in mucosal inflammation positions this receptor as a promising, mechanistically anchored therapeutic target in Crohn's disease.

Piezo1 ion channels play a crucial role in apoptosis regulation in human breast cancer cells (MCF-7), and this study evaluates the effects of Piezo1 agonist (Yoda1), inhibitor (GsMTx4), and ultrasound microbubble (USMB) treatment on cellular apoptosis pathways. In this research, in vitro cultures of normal breast epithelial cells (MCF-10A) and cancer cell lines (MCF-7, MDA-MB-231) were analyzed by Western blotting to determine Piezo1 protein levels, with MCF-7 selected for further analysis. Groups included control (untreated), Yoda1, USMB, GsMTx4, and USMB+GsMTx4, and apoptosis rates were measured via flow cytometry. Levels of apoptosis-related proteins (Bcl-2, Bax), endoplasmic reticulum stress proteins (GRP-78, Caspase 12), and mitochondrial pathway proteins (Cyt-c, Caspase 3, Caspase 9) were quantified, while JC-1 and Ca2+ fluorescent probes were used to assess mitochondrial membrane potential and intracellular Ca2+ concentration. Results showed MCF-7 cells expressed the highest Piezo1 levels. Yoda1 and USMB both markedly increased apoptosis, enhanced ER stress, and induced the mitochondrial apoptosis pathway in comparison to control, while GsMTx4 had the opposite effect and USMB reversed GsMTx4's phenotype. The USMB group exhibited the lowest mitochondrial membrane potential and the highest Ca2+ fluorescence intensity. These findings indicate that USMB activates ER stress via Piezo1, induces mitochondrial dysfunction, elevates intracellular Ca2+, and thereby promotes apoptosis in breast cancer cells.​​.

Necroptosis, a lytic type of cell death that is dependent on RIPK1-activated RIPK3 and MLKL, has been implicated in the progression of septic shock-related events. However, the role of RIPK1/RIPK3/MLKL necrosome in hemodynamic alterations associated with necroptotic and inflammatory tissue injury due to bacterial infections has not been explored. Therefore, we aimed to investigate whether inhibition of the RIPK1-driven necroptosis by a selective inhibitor of RIPK1, Nec-1s, protects against hypotension and tachycardia associated with necroptotic-, inflammatory-, and injury-related changes induced by bacterial LPS in rats. We also investigated the effects of RIPK1 inhibition on TLR4/TRIF- and caspase-8-related pathways that may contribute to these changes induced by LPS. The MAP and HR values were recorded from the conscious animals using a tail-cuff method. Serum iNOS, HMGB1, MPO, and LDH levels were determined using ELISA kits. The immunoblotting method was used to determine the changes in the expression of proteins related to the TLR4/TRIF- and caspase-8-mediated necroptotic and inflammatory pathways in the TA, RA, PA, and MCA. In the heart, kidney, lung, and brain, histopathological changes were evaluated by the H&E staining method. Expression of RIPK1, RIPK3, MLKL, and HMGB1 proteins in these organs was determined using immunohistochemical staining. Nec-1s prevented LPS-induced hypotension and tachycardia, increased serum iNOS, HMGB1, MPO, and LDH levels as well as expression of unphosphorylated and/or phosphorylated proteins of TLR4/TRIF/RIPK1/RIPK3/MLKL/HMGB1-, TLR4/MyD88/TAK1/IKKβ/NF-kB/iNOS/NO/VASP-, and caspase-8-related pathways in the arterial vasculature, but did not increase RIPK1, RIPK3, and MLKL protein expression induced by LPS in the heart, kidney, and lung tissues. The LPS-induced increase in scores related to histopathological changes in the kidney was attenuated by Nec-1s. These findings suggest that inhibition of the RIPK1-driven necroptosis protects against hypotension and tachycardia, along with arterial and/or renal necroptotic-, inflammatory-, and injury-related changes during septic shock. It also seems that suppression of the TLR4/TRIF- and caspase-8-related pathways may contribute to the beneficial effects of Nec-1s during septic shock.

The discovery of selective inhibitors of factor XIIa (FXIIa) is an attractive approach for development of new antithrombotics that do not interfere with normal hemostasis. Here we report an in vitro chromogenic assay and in silico molecular modeling-based integrated protocol for predicting the inhibitory aptitude of natural flavonoids, Fisetin, Morin, Rutin and the synthetic derivative (FXIIa-IN-4) of the FXIIa enzyme. The frontier molecular orbitals (FMO) analysis, accompanied by the electrostatic potential (ESP) maps and a non-covalent interaction (NCI) map, provided the information about electronic reactivity of the title compounds. Chromogenic assays data of assessed flavonoids, Fisetin, Morin and Rutin have been shown a dose-dependent inhibition of FXIIa activity, in which at higher concentration (1000 µM) they exhibited about 52.6%, 57.1% and 71.9% inhibition, respectively. Molecular docking studies showed that Rutin has the lowest binding energy with FXIIa (8.6 kcal/mol) and Fisetin has with optimal balance between affinity, structural compactness and reactivity. In addition, molecular dynamics enables comparison of the stability and flexibility of the various ligand-protein complexes. Fisetin is the ligand that provides best structural stability, and Rutin causes a greater conformational variation, but with more hydrogen bond interactions. A detailed absorption, distribution, metabolism, and excretion (ADMET) analysis revealed that FXIIa-IN-4 has the best ADMET profile, while Fisetin is the second. Morin and Rutin, on the other hand, were found to have less clear toxic effects. Taken together, although the in vitro chromogenic assessment results demonstrated that Rutin has superiority in inhibition of FXIIa enzyme activity, the overall obtained data indicated the importance of Fisetin among all tested flavonoid compounds as an equilibrative natural inhibitor demanding in vivo experimental confirmation and focused molecular modification.

Plasmodium falciparum is the most dangerous malaria parasite affecting humans. Compounds such as mukonal, 7-hydroxymukonal, and 7-methoxymukonal have shown potential for the treatment of this disease. Density Functional Theory (DFT), molecular docking, and pharmacokinetic analyses are valuable computational approaches for predicting potential drug candidates against P. falciparum. In this study, three compounds mukonal, 7-hydroxymukonal, and 7-methoxymukonal were optimized and evaluated through molecular docking and pharmacokinetic analysis against the target protein PF3D7_1441900 (transcription factor TFIIH complex subunit Tfb5, putative) from P. falciparum isolate 3D7. Frontier molecular orbital and density of states analyses revealed that 7-methoxymukonal has a relatively smaller energy gap compared with the other two compounds. In addition, 7-methoxymukonal exhibited the strongest binding affinity toward the target protein. The ADME results indicated favorable drug-like properties and low toxicity, further supporting the therapeutic potential of these compounds. Overall, our theoretical findings suggest that compound 3, namely 7-methoxymukonal, is the most promising candidate against the selected protein, in agreement with the other computed parameters.

The study aimed to evaluate the antioxidant properties, chemical composition, and total phenolic and flavonoid contents of the stembark from Breonadia salicina. Furthermore, lead compounds were studied for their possible antioxidant and anticancer effects using in silico analysis. Antioxidant activity was measured using the ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays. The chemical composition was analyzed with LCMS/LC-HRM (Liquid Chromatography-High Resolution Mass Spectrometry) technique. The ethyl acetate (EAS) fraction derived from Stembark exhibited significant antioxidant properties, as evidenced by its total phenolic content (146.8 ± 1.2 mg GAE/g), flavonoid contents (84.7 ± 4.6 mg Rutin/g), DPPH and ABTS radical scavenging activity, yielding values of 279.7 and 259 μg/mL, respectively. A total of twenty-one compounds were identified within the EAS fraction. Notably, compounds 7, 18, and 19 recorded the highest docking scores of -9.2, -9.2, and -9.3 (kcal/mol, respectively. Compounds 1, 5, 8, 9, and 13 demonstrated significant cytotoxicity against ovarian cancer, with a probability (Pa) greater than 0.92. Furthermore, compounds 1, 2, 3, 6, 8, 9, 10, 12, 15, 19, and 21 exhibited strong IC50 values of less than 1 µM. Among these, compounds 1 and 19 received the highest predictive scores from the three in silico assessment tools employed. Anacardic acid (compound 1) and SSR161421 (compound 19) achieved the best results, being recognized by two of the three anticancer in silico tools. These lead compounds may serve as promising candidates for the development of therapeutic agents aimed at specifically targeting cancer cells.

Human epidermal growth factor receptor 2 (HER2) is one of the key drivers of oncogenesis in HER2+ breast cancer. The overexpression resulted in uncontrollable cell division and additional tumor growth. Despite the current clinical therapeutics such as Tucatinib, Lapatinib, and Neratinib, the demand for novel inhibitors still exists. The research aimed to employ a multi-step computational framework for the discovery of highly effective small molecule inhibitors. The crystal structure of HER2 (PDB: 3PPO) was retrieved, and subsequently, virtual screening of small molecules was carried forward with the Mcule library. The screening resulted in filtering 100 compounds, out of which 45 were found to be non-toxic and had good ADME properties. BOILED-egg analysis predicted favorable HIA and BBB permeability properties surpassing the performance of clinically approved HER2 inhibitors. The docking studies singled out 11 compounds that had a high affinity towards the protein. On filtering those, the top two compounds achieved the best binding energies of -9.9 kcal/mol and -9.8 kcal/mol, respectively, outperforming the reference inhibitors. Moving ahead, 100 ns MD simulations confirmed enhanced stability, lower RMSF values, higher compactness, better solvation free energy, and persistent hydrogen bonding throughout the simulation period, showing the comparable results to the inhibitor. In comparison, findings reveal that Compound 1 hits structurally and energetically outperforming the existing therapeutics. Compound 2 showed a little less impact than compound 1, but can be considered as well as surpassing all the parameters successfully. Thereby, making the potential lead candidates for further experimental validation in breast cancer therapy.

Rapid eye movement (REM) sleep is a critical phase in which most dreaming occurs, and its deprivation (REM SD) can lead to disturbances in mood, cognition, synaptic plasticity, and neuroplasticity-related genes such as brain-derived neurotrophic factor (BDNF). Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is known to modulate BDNF expression, and sex-dependent variations in its effects have been suggested. This study investigated the effects of REM SD, fluoxetine, and their combination on behavioral and molecular outcomes in male and female rats. Results: Following 24 hours of REM SD, animals exhibited impaired memory, increased immobility, reduced rearing, elevated pain threshold, and decreased locomotor activity, along with reduced BDNF levels in the prefrontal cortex. Females were less sensitive to REM SD regarding pain threshold and locomotor activity. Fluoxetine administration (10 mg/kg, i.p.) reversed the effects of REM SD on immobility and rearing exclusively in females, while also mitigating locomotor deficits induced by REM SD. In both sexes, fluoxetine counteracted REM SD-induced changes in pain threshold, but only in females did it restore BDNF downregulation. In conclusion, the findings suggest sex-specific variations in the consequences of REM SD and in the therapeutic response to fluoxetine. While REM SD broadly impairs cognitive, affective, and molecular parameters, females exhibit partial resilience, particularly in pain threshold and locomotor activity. Moreover, fluoxetine demonstrates sex-dependent protective effects, especially in restoring BDNF expression and behavioral outcomes in females.

Cancer is the leading cause of morbidity and mortality globally, underscoring the need for precise diagnostic approaches and effective therapeutic strategies. The invention of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system has transformed cancer research by enabling accurate and efficient genome editing. This review provides a comprehensive overview of CRISPR-based applications in cancer therapeutics and diagnostics, beginning with an introduction to cancer biology and the CRISPR/Cas9 mechanism of action. The therapeutic potential of CRISPR is discussed with a focus on targeting oncogenes, restoring tumor suppressor gene function, and advancing cancer immunotherapy through approaches such as CAR-T cell engineering. The use of CRISPR-based screening platforms to identify genes associated with drug resistance is also examined, along with current challenges including off-target effects, delivery limitations, and ethical considerations, as well as future directions for clinical translation. In addition, the diagnostic capabilities of CRISPR technologies are highlighted, including the detection of circulating tumor DNA, cancer-associated extracellular vesicles, protein biomarkers, and microRNAs. Recent advances in CRISPR/Cas-based strategies aimed at improving detection sensitivity and specificity are summarized. Overall, this review highlights the expanding role of CRISPR systems in cancer diagnosis and therapy and emphasizes their potential to contribute to the development of more personalized and effective cancer management strategies.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths globally. It results from polyp growth or ulcers formation in the colon or intestine lining. Genetic, environmental factors, unhealthy eating habits, and lifestyle choices contribute to CRC development. Genetic and epigenetic changes play a crucial role in tumor development. Homeobox (HOX) genes contain the homeodomain, encoding transcription factors that regulate gene expression. Paired Related Homeobox 1 (PRRX1) and Paired Related Homeobox 2(PRRX2), a homeobox genes, is overexpressed in diseases and involved in tumor metastasis, impacting cancer cell properties and metastasis. In this study, our goal was to analyze the presence of PRRX1and PRRX2 in both colorectal cancer and nearby normal tissues. The expression levels of PRRX1 and PRRX2 were evaluated in 100 colorectal tumor tissues and 100 adjacent control tissues using the Quantitative Real-Time PCR (qRT-PCR) method. Additionally, we assessed the diagnostic effectiveness of PRRX1 and PRRX2 by creating a receiver operating characteristic (ROC) curve. Our findings showed that the expression of PRRX1 and PRRX2 were significantly overexpress in colorectal cancer patients compared to the adjacent control group sample. Examination of clinicopathological characteristics of patients revealed varied correlations between PRRX1 and PRRX2 genes expressions and TMN stage (p<0.0001, p<0.0001). Also, the expression levels of PRRX1, PRRX2 between patients with LVI+ and those with LVI-, with p-values of p<0.0001, p<0.0001 for each. These findings suggest that PRRX1and PRRX2 levels could be used as possible diagnostic indicators for colorectal cancer.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system with limited treatment efficacy for progressive forms. Mesenchymal stem cells (MSCs) and their secreted exosomes offer therapeutic potential via regenerative and immunomodulatory actions, including T-cell suppression and neurotrophic factor secretion. Exosomes, as cell-free alternatives, may mediate MSC effects by delivering cargo such as microRNAs, potentially promoting oligodendrocyte precursor cell differentiation and blood-brain barrier stabilization with reduced immunogenicity. Preclinical experimental autoimmune encephalomyelitis models and early MSC clinical trials demonstrate promise in reducing disease severity, although optimization of exosome sources, delivery routes (intrathecal versus intravenous), dosing, and standardization remains a challenge for clinical translation. Here, we describe a 44-year-old female with a 21-year history of progressive MS unresponsive to interferon beta-1a and Ocrelizumab, who presented with widespread neurological deficits, including sensory disturbances, weakness, and urge incontinence. Examination revealed ataxia, intention tremor, and hyperreflexia, with previous MRIs confirming MS plaques. In 2025, she received allogeneic umbilical cord-derived MSC exosomes (1 cc intrathecally; 1 cc intravenously at half dose) with adjunctive intravenous laser therapy. Within three weeks, she reported 70-80% symptomatic improvement, including resolution of Lhermitte's sign and enhanced muscle strength, vision, memory, and energy. Two-month follow-up MRIs showed persistent lesions without new contrast enhancement, indicating no active disease progression. This case highlights significant symptomatic improvement in long-standing progressive MS following combined intrathecal and intravenous allogeneic UC-MSC exosome administration. The rapid clinical benefits and absence of new MRI activity suggest a potential modulatory role for exosome therapy in MS, although these encouraging findings from a single case with adjunctive therapy necessitate larger, controlled clinical trials to validate efficacy, safety, and optimal protocols, and to elucidate underlying mechanisms.

Mentha longifolia (horsemint) and Mentha spicata (spearmint) are economically valuable aromatic plants widely utilized in food, cosmetic, and pharmaceutical industries due to their rich reservoir of bioactive compounds. This study investigated the antifungal and antibiofilm properties of essential oils extracted from these species against various Candida strains, particularly Candida albicans, a major opportunistic pathogen responsible for oral and systemic infections. Essential oils were extracted via hydrodistillation using a Clevenger apparatus and chemically characterized through GC-MS, revealing that M. longifolia oil was predominantly composed of pulegone (29.7%), menthone (26%), and eucalyptol (17.8%), while M. spicata oil was mainly enriched in pulegone (68.5%), eucalyptol (5.2%), and thymol (3.5%). The antifungal activity, evaluated by agar-well diffusion and broth microdilution assays, showed inhibition zones ranging from 9-14 mm for M. longifolia and 9-12 mm for M. spicata, with corresponding minimal inhibitory concentrations (MICs) of 0.39-6.25 mg/mL and fungicidal concentrations (MFCs) of 12.5-100 mg/mL. Both oils markedly reduced biofilm biomass in a concentration-dependent manner, with up to 90% inhibition observed at 4&#xd7; MIC. The potent biofilm disruption was attributed to the high terpenoid content, capable of altering fungal membrane integrity. Overall, these findings demonstrate that the essential oils of M. longifolia and M. spicata possess significant antifungal and antibiofilm potential, highlighting their possible application as natural, plant-derived therapeutic agents for controlling Candida-associated oral and biomedical infections.

Increasing hepatic lipid accumulation is the primary cause of non-alcoholic fatty liver disease (NAFLD), which has become an emerging health concern globally. Many studies have used the HepG2 cell-based in vitro model of NAFLD to investigate intracellular lipid accumulation after several hours of exposure to free fatty acids (FFAs). However, the molecular mechanisms underlying the early onset of lipid accumulation are yet to be unveiled. In this study, we examined oleic acid (OA) and palmitic acid (PA)- induced lipid accumulation in HepG2 cells at early time points, i.e., in minutes. Using Oil Red O staining and fluorescence microscopy imaging, we observed a time-dependent increase in intracellular lipid accumulation in cells treated with 0, 0.25, 0.5, and 1.0 mM FFAs. Notably, significant lipid droplet formation was detected within 15 min of OA treatment at 0.5 and 1.0 mM concentrations compared to the control, whereas PA did not elicit such an early response. Gene expression analysis revealed upregulation of genes related to lipid metabolism (SREBF1, PDK4, and G6PC), beta-oxidation (CPT1a) and cholesterol synthesis (HMGCR) at the early time point. Additionally, immunoblot analysis showed increased expression of Fatty acid synthase (FASN), which is a well-known marker of lipogenesis. In summary, our findings indicate that OA induces lipid accumulation more robustly than PA at early time points, providing insights into the molecular changes at the onset of NAFLD progression.

Cervical cancer is a multifactorial disease like any other human cancer. Among these factors, genetic polymorphisms of Glutathione S-Transferase Mu1 (GSTM1) have been incriminated, but the studies results remain controversial. The objective of this meta-analysis was to study the influence of GSTM1 polymorphisms on the occurrence of cervical cancer and to explore interactions between genes and human papillomavirus (HPV) infection and exposure to tobacco smoke. A meta-analysis was conducted on studies published up to June 12, 2025, from six databases: ScienceDirect, Embase, Scopus, PubMed, Google Scholar, Web of Science. Eligible studies included all case-control investigations that assessed the association between GSTM1 polymorphisms and the risk of cervical cancer. Odds ratios and confidence intervals from the studies were used to estimate the combined effect size. Statistical analyses were conducted using both the DerSimonian and Laird random-effects model and Mantel and Haenszel fixed-effect model with a 95% confidence interval. Subgroup analyses were performed to identify potential sources of variability. A significant association was observed between the GSTM1-null and an increased risk of Cervical Cancer (ORCC=1.47, Pz=0.011) and Squamous Intraepithelial Lesions (ORSIL=1.42, Pz=0.035) compared with the GSTM1-present. The included studies showed high heterogeneity. Overall, carriers of the GSTM1-null had a higher likelihood of developing Cervical Cancer compared to carriers of the GSTM1-present. In subgroup analyses, an increased risk associated with the GSTM1-null was found among Asian populations (ORCC=1.54, Pz=0.002) and according to sample type, in blood DNA extracts (ORCC=1.27, Pz=0.052). Furthermore, the GSTM1-null was associated with increased risk in HPV+ women (ORCC=4.88, Pz=0.005) and in women exposed to tobacco smoke (ORCC=1.35, Pz=0.033). According to histological type, GSTM1-null was also associated with the development of Squamous Cell Carcinoma (ORSCC=1.52, Pz=0.020). in conclusion, GSTM1-nullwere associated with an increased risk of cervical cancer in women, especially in HPV+ women and those exposed to tobacco smoke.

It is currently known that meniscal damage has a bidirectional relationship with the onset/development of osteoarthritis (OA), making the development of new therapeutic strategies that comprehensively address both issues crucial. In this context, the present study aimed to evaluate the biological effect of peniocerol (PEN), an emerging phytopharmaceutical, in an in vitro model of inflammation induced by IL-1&#x3b2; and TNF-&#x3b1; in human meniscal fibrochondrocyte cells. Human meniscal fibrochondrocyte cells were isolated, cultured, and treated with different concentrations of PEN to determine those that promote cell proliferation and the IC&#x2085;&#x2080; using the MTT assay. The cells were then stimulated with TNF-&#x3b1; (10 ng/mL) or IL-1&#x3b2; (5 ng/mL), with or without PEN (300 and 500 &#xb5;M). Cell morphology and the expression of ACAN, type I+III collagen, type II collagen, MMP13, and p65 were evaluated by immunofluorescence. Treatment with TNF-&#x3b1; and IL-1&#x3b2; significantly reduced the expression of ACAN and type II collagen, while increasing MMP13 and p65, indicating a degenerative phenotype. Co-treatment with PEN at 300 &#x3bc;M showed partial improvements, while PEN at 500 &#xb5;M normalized the levels of ACAN, Col2A1, and p65 to values similar to the control, while significantly inhibiting the markers for COL I+III and MMP3. In an in vitro degenerative fibrochondrocyte model, PEN at 500 &#x3bc;M demonstrated its ability to halt extracellular matrix degradation and actively promote its recovery, showing an optimal balance between efficacy and safety as a potential therapeutic strategy for the comprehensive treatment of OA progression.

Cancers of the brain and nervous system are among the top five most common malignancies affecting both men and women in Iraq. Improvements in diagnostic techniques alongside increased medical awareness have facilitated earlier detection, thereby potentially improving patient outcomes. Cancer stem cells (CSCs) have been recognized as key players in the initiation, progression, and recurrence of tumors, including glioblastoma, the most aggressive form of brain cancer. These CSCs are characterized by specific markers that contribute to tumor growth, resistance to therapy, and poor prognosis. In this study, we collected 26 glioma tissue samples from Iraqi patients and classified them according to tumor grade. Using immunohistochemical methods, we investigated the expression patterns of three important CSC markers-ALDH1A1, CD44, and OCT3/4-across different glioblastoma grades. Our findings demonstrated a significant upregulation of cytoplasmic ALDH1A1 and membrane-bound CD44 in higher-grade tumors (grades III and IV), with P-values of less than 0.0174 and 0.0013, respectively. Additionally, nuclear OCT3/4 expression was markedly increased in these advanced tumor grades (P < 0.05), suggesting a role in tumor aggressiveness and stemness. These data provide compelling evidence that ALDH1A1, CD44, and OCT3/4 are not only involved in glioblastoma progression but may also serve as useful prognostic biomarkers. Furthermore, their elevated presence in more malignant tumors highlights their potential as targets for novel therapeutic interventions aimed at improving treatment efficacy and patient survival. This study thus contributes valuable insights into the molecular landscape of glioblastoma in the Iraqi population and sets a foundation for future research in targeted cancer therapy.

The emergence of Coronavirus Disease 2016 (COVID-16), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly escalated into a global pandemic, resulting in millions of confirmed cases and deaths worldwide. The objective of this study was to examine the effects of vitamin D and vaccination on mortality and disease severity in patients with COVID-16. In this cross-sectional study, we observed the suspected and confirmed admitted patients with COVID-19 for the possible outcomes after admission to the hospital. The study included patients with a mean age of 71.01 years (range: 28-66), predominantly aged &#x2265;60 years (85.14%) and male (85.05%). Most patients were unvaccinated (77.03%) upon admission. Admission duration ranged from 1-30 days, with the highest proportion staying 8-14 days (36.16%), followed by 1-3 days and >14 days (each 21.62%). Symptoms appeared 1-46 days pre-admission (median: 8 days). Disease severity was critical (41.86%), severe (28.38%), moderate (25.68%), and mild (4.05%). All patients required oxygen. Mortality was 54.05%, 32.43% were discharged unknown, and 13.51% recovered. Key comorbidities included hypertension (66.22%), diabetes (37.84%), IHD (25.68%), smoking (21.62%), and CKD (12.16%). Universal fever presentation included persistent (44.63%) and moderate (28.66%) types. Common symptoms were shortness of breath (66.67%), cough (75.68%), chest pain (60.81%), fatigue (52.7%), and anorexia (50.0%). Vaccination (22.67%) and vitamin D status showed no significant association with disease severity or outcomes. Most patients were elderly, male, unvaccinated, and had comorbidities; high mortality was observed, with no significant association between outcomes and vaccination or vitamin D status.

This study aimed to evaluate the effects of ethanolic extract of dried Moringa oleifera leaves (MO) administered intragastrically at different doses for 30 days on diabetes-induced amnesia and hyperalgesia in rats, as well as to investigate the possible underlying mechanisms. Rats received MO extract (100, 200, and 400 mg/kg) or vehicle starting at the onset of hyperglycemia and continuing for 30 days. Passive avoidance learning (PAL) and memory tasks were used to assess memory, while formalin test was applied to analyze chemical hyperalgesia. Diabetes led to impairments in both phases of the PAL and memory test. MO (200 and 400 mg/kg) protected diabetic rats from learning and memory impairment and enhanced cognition of control animals. In the formalin test, MO at 200 and 400 ng/kg reversed chemical hyperalgesia of diabetic rats, while showing analgesic effects in healthy rats. The most significant hypoglycemic and antioxidant effects were shown with MO 400 mg/kg in diabetic animals. MO (200 and 400mg/kg) enhanced cognitive function and induced analgesia in diabetic rats, possibly by hypoglycemic and antioxidant mechanisms. Therefore, it may be a promising source for management of diabetic neurological complications that deserves notice and further studies.

Receptor activator of nuclear factor-&#x3ba;B ligand (RANKL) is a key mediator linking inflammation to osteoclast activation and bone erosion in rheumatoid arthritis (RA). Evidence on circulating RANKL levels and RANKL (TNFSF11) polymorphisms in RA has been inconsistent. Web of Science, Scopus, and PubMed were searched from inception to December 2025 for clinical studies comparing patients with RA and healthy controls and reporting either serum/plasma RANKL concentrations and/or RANKL genotype/allele distributions. Mean differences (MD) were pooled for circulating RANKL, and odds ratios (OR) were pooled for polymorphisms under allelic, dominant, and recessive models. Ten studies (908 RA; 525 controls) were included for serum RANKL. Serum RANKL was higher in RA than controls (pooled MD 8.16, 95% CI 3.90-12.41). For genetic analyses, three SNPs were eligible for pooling. rs9533156 showed a significant association with RA in the allelic (C vs T: OR 0.82, 95% CI 0.70-0.97) and dominant models (CC+CT vs TT: OR 0.77, 95% CI 0.61-0.98). rs2277438 showed a borderline allelic association (OR 1.21, 95% CI 1.00-1.45) and model-dependent results for the recessive contrast with heterogeneity. RA is associated with increased circulating RANKL, while genetic associations appear SNP-specific, with the most consistent evidence observed for rs9533156. Larger, multi-ethnic studies with standardized biomarker measurements are needed.