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Breast cancer is one of the leading causes of death in women worldwide, highlighting the crucial need for novel and effective treatments. In this study, we look at the ability of four natural compounds i.e. Berberine, Curcumin, Withaferin A, and Ellagic Acid to target important breast cancer biomarkers such as B-cell lymphoma 2 (BCL-2), programmed death-ligand 1 (PDL-1), cyclin-dependent kinase 4/6 (CDK4/6) and fibroblast growth factor receptor (FGFR). These indicators have important roles in tumor development, survival, immune response, and cell cycle control, making them potential targets for future cancer treatments. Our study employs a variety of techniques, including pharmacokinetic profiling (ADME), molecular docking, and molecular dynamics simulations, to determine how successful these drugs could be in therapy. The pharmacokinetic investigation found that Berberine and Ellagic Acid stand out due to their high absorption and solubility, implying that they could be suitable for clinical application. When we ran docking simulations, we discovered substantial connections between these chemicals and the target proteins. Additionally, Berberine has a binding affinity of − 9.3 kcal/mol for BCL-2, indicating that it can impair the protein’s cancer cell-protective activities. Ellagic Acid, on the other hand, has an even higher binding affinity for PDL-1 of − 9.8 kcal/mol, showing that it may be able to increase immune responses against tumors. Molecular dynamics simulations over 100 ns demonstrated the stability of these protein–ligand complexes. Interestingly, Ellagic Acid was found to be more structurally stable than Berberine throughout these simulations. We found consistent interactions between the chemicals and key residues in the target proteins. For example, Ellagic Acid (CID: 5281855) established persistent linkages with LYS43, ASP163, and VAL27, whereas Berberine (CID: 2353) interacted with VAL27, ALA41, and LEU152 throughout the simulation. In conclusion, the combination of good pharmacokinetics, robust interactions with cancer biomarkers, and stable complexes makes Berberine and Ellagic Acid interesting candidates for further investigation as natural inhibitors in breast cancer treatment. These findings establish the framework for future research into novel and inventive techniques to effectively combating breast cancer.

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea ( BPU ), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC 50  = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored − 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and − 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

In recent decades, the rate of infection with dengue virus (DENV) has risen significantly, now affecting nearly 400 million individuals annually. Dengue fever among humans is caused via specific mosquito vectors bites. Sporadic cases have been reported in Egypt. The goal of this study was to identify the serotype of the DENV outbreak in both human and mosquito vector along the coast of the Red Sea, Upper Egypt, in 2017. Identification of the serotype of the virus may help identify its source and assist in applying epidemiological and control measures. The current study was carried out in El Quseir City, Red Sea Governorate, Upper Egypt, on 144 patients complaining of symptoms indicative of dengue fever at the time of the 2017 Egypt outbreak. Human blood samples and the mosquito reservoirs were identified as having dengue virus infection serologically and molecularly. Overall, 97 (67.4%) patients were positive for dengue virus IgM antibodies. Molecular examination of the human samples and pools of mosquitoes revealed that DENV-2 virus was the serotype responsible for the outbreak. Only one pool of female mosquitoes containing was infected with dengue fever virus (DENV-2). This was the first serotyping of the DENV responsible for dengue virus outbreak in Egypt in 2017. Determining the serotype of dengue virus can help to avoid and monitor outbreaks. The serotype identified in this study was DENV-2, while DENV-1 was the serotype found in the previous outbreak in 2015 in the province of Assiut. This study thus raises concerns that a new dengue serotype could have been introduced into Egypt. It is necessary for a comprehensive risk assessment to be carried out in the country, including an entomological survey, to assess the presence and potential geographical expansion of mosquito vectors there.

Although it looks reasonable to say menopausal women experience significant changes in quality of life, however the period is filled with anxiety and distress. Women can experience an array of symptoms including hot flushes, night sweats, sleep and mood disorders, impaired memory, lack of concentration, nervousness, depression, insomnia, bone and joint complaints Objectives:1. To assess Quality of life in menopausal women attending primary health care centers of Jazan, KSA 2. To conduct factor analysis for the variables affecting quality of life of menopausal women Methodology: A cross-sectional study conducted in primary health centers located in Jazan city. All menopausal women between age of 40-79 years were considered. A predesigned questionnaire drawn from World Health Organization Quality Of Life BREF (WHO QOL BREF) utilized Results: Mean age was 50.02+4.5 (Age + SD) Physical changes domain mean was 1.42+1.46 (mean + SD), greater than other domains and the participants were experiencing physical changes affecting quality of life more than any domain Sexual changes domain mean + SD was 1.21+1.99 and the participants were extremely bothered with symptoms of this domain. Conclusions: Significant shift in health care services is required for improving QOL of menopausal women which continue to be overlooked.

Unmet need for contraception remains a persistent global reproductive health challenge. In Saudi Arabia, national estimates indicate moderate contraceptive uptake; however, region-specific data on awareness, accessibility, and utilization of family planning (FP) services remain limited, particularly in semi-rural settings such as Al-Baha. To evaluate awareness, access, and utilization of family planning and reproductive health services and to identify perceived barriers and sociodemographic determinants among adult women in Al-Baha, Saudi Arabia. A population-based cross-sectional study was conducted using a 23-item online questionnaire administered to female residents aged ≥18 years between December 2024 and February 2025 through convenience sampling. Descriptive statistics summarized participant characteristics and FP-related variables. Associations between categorical variables were assessed using chi-square ( ²) tests. Univariable and multivariable logistic regression analyses were performed to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at a two-sided  < 0.05. Ethical approval was obtained from the Deanship of Scientific Research, Al-Baha University (Approval No. 46110701-20241117), and electronic informed consent was secured prior to participation. A total of 892 women participated (mean age 38 ± 10.5 years). Awareness of FP initiatives was reported by 24%, and 18% had previously received FP consultation/services. Although 94% reported geographic access to a healthcare facility within 30 min, routine reproductive health service utilization remained limited, with 53% reporting infrequent visits. Current contraceptive use was reported by 42%, predominantly oral contraceptive pills (15%) and intrauterine methods (9%). Overall, 32% reported at least one barrier to contraception access, with \"other barriers\" (14%) and limited availability (11%) cited most frequently. Several outcomes demonstrated significant sociodemographic variation (  < 0.05). In multivariable analysis, age >30 years independently predicted current contraceptive use (aOR 3.97; 95% CI 2.64-5.98;  < 0.001). Despite reported geographic accessibility, awareness and counselling uptake remain suboptimal in Al-Baha. Targeted, culturally responsive primary care-based interventions and strengthened service availability are warranted to improve informed reproductive health decision-making.

Background: Research is ongoing to better understand the immune response and the role of cytokines in COVID-19's pathogenicity and clinical heterogeneity. Objectives: This study aimed to assess the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-6, IL-10, and IL-4 in the blood of patients infected with severe acute respiratory syndrome (SARS)-CoV-2 in Kassala State, Eastern Sudan, compared to healthy individuals residing in the same state. Methods: This case-control study was conducted on 90 adult patients with COVID-19 infection at Kassala Teaching Hospital (KTH), confirmed by RT-PCR, and compared to 90 age- and sex-matched healthy subjects as controls. Serum samples were collected and analyzed for cytokine levels using the enzyme-linked immunosorbent assay (ELISA). Results: The levels of TNF-α, IL-17, and IL-10 in patients were significantly higher (P = 0.021, 0.000, and 0.015, respectively) than those in the control group. Conversely, the IL-4 levels were significantly lower (P = 0.000) in patients than in controls. A comparison between mild, moderate, and severe groups showed that the levels of TNF-α and IL-10 were higher in the severe group than in the mild and moderate groups, whereas the levels of IL-4 decreased with increasing disease severity without reaching significant differences. Tumor necrosis factor-α, IL-17, and IL-4 could predict the disease severity of 2019-nCoV infections according to the area under the curve (AUC) of the receiver operating curve (ROC). Conclusions: Our findings suggest that TNF-α, IL-17, IL-10, and IL-4 can serve as indicators and reliable predictors of severe illness in Sudanese patients with COVID-19.

El-Kady AM, Osman HA, Alemam MF, et al. Infect Drug Resist. 2022;15:2713-2721. The authors have advised that the acknowledgment statement on page 2719 is incorrect. The text “This research was supported by Princess Nourah Bint Abdulrahman University Project number (PNURSP2022R39), Riyadh, Saudi Arabia” should read “This research was supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R39), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia”. The authors apologize for this error.

Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the mutations result in complex alterations of the immune system in addition to MC deficiency. We revisited the role of MCs in vaccination responses using and mice that lack connective tissue MCs or all MCs, respectively, but feature an otherwise normal immune system. These animals showed no impairment of T and B cell responses to intradermal vaccination with protein antigen plus complete Freund's adjuvant. Moreover, we demonstrate that the adjuvant effects of the MC secretagogue c48/80 in intradermal or mucosal immunization are independent of the presence of MCs. We hence find no evidence for a regulation by MCs of adaptive immune responses to protein antigens. The finding that immunological MC functions differ from those suggested by experiments in mutants, emphasizes the importance of rigorous tests in Kit-independent MC-deficiency models.

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored - 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and - 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored - 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and - 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

Hyperekplexia “startle disease” is a neurological disorder that is primarily caused by hereditary mutations disrupting the inhibitory signals in the spinal cord. The Glycine receptor, GlyR, α-subunit GLRA1 gene is the main site of these mutations. As a result, GlyR loses its function of chloride channel due to decreased sensitivity to glycine, reduced surface expression, decreased current, or fast channel closure. The V280M mutation in GlyR-α1 subunit causes hyperekplexia but, surprisingly, these receptors showed a gain of function. The mutation produced spontaneous channel activity, increased glycine sensitivity, with no apparent reduction in the membrane expression. We investigated possible mechanisms for V280M α1GlyR in causing hyperekplexia. We took two approaches. Using electrophysiology, we found that the increased sensitivity of the receptor to glycine led to increased occupancy of the desensitized state. We conditioned α1GlyR with low concentrations of glycine, followed by activating the receptors by a saturating concentration of glycine. We found that 10µM glycine, the concentration present in cerebrospinal fluid (CSF), desensitized > 98% V280M α1GlyR compared to 30% of wild type α1GlyR. Using Number and Brightness imaging of SNAP-tagged GlyR; we monitored receptor oligomerization and receptor association with the anchoring protein gephyrin to form clusters. V280M α1GlyR formed larger oligomers than did wild type α1GlyR. However, V280M α1GlyR harboring gephyrin binding domain did not form clusters when associated with gephyrin, unlike wild type α1GlyR harbor gephyrin binding domain formed clusters when coexpressed with gephyrin. In conclusion, although V280M α1GlyR displays a gain of function, exposure of V280M α1GlyR to CSF levels of glycine would desensitize most of the receptors between synaptic signaling. Furthermore, V280M α1GlyR did not form clusters when associated with gephyrin, suggesting that V280M α1GlyR might fail to localize at the synapse.