Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson's disease in a rat model: Involvement of multiple pathways.

BACKGROUND: Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain. OBJECTIVES: To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2-induced Parkinson's disease (PD). METHODS: Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II-Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo-treated plants. RESULTS: ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ-amino butyric acid content and markedly improved the brain levels of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and decreased glycogen synthase kinase-3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa-light-chain-enhancer of activated B cells, Toll-like receptor 4, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 and caspase-1. Bcl-2-associated X-protein and B-cell leukemia/lymphoma 2 protein (Bcl-2) can significantly modify caspase-3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p-protein kinase-like ER kinase (PERK), glucose-regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin-1). DISCUSSION AND CONCLUSION: ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti-inflammatory, antioxidant, and anti-apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl-2 pathway.

Insights and perceptions: Investigating pregnant women's attitudes, understanding, and factors influencing knowledge regarding medication usage during pregnancy-A cross-sectional study.

BACKGROUND: Medication use during pregnancy is a critical concern due to potential risks to both the mother and fetus. To the extent of our knowledge, there has been no prior research to assess medication use and identify the specific factors of pregnant women within the Yemeni community. This study aimed to investigate the knowledge, beliefs, and practices of Yemeni pregnant women regarding medication use and assess the factors associated with the knowledge during pregnancy. METHODS: A cross-sectional multi-center study was conducted through face-to-face interviews using a validated structured questionnaire. The study was conducted on pregnant women receiving antenatal care at tertiary care hospitals in four governorates in Yemen. Univariable and multivariate logistic regressions were employed to examine the relationship between participant variables and their knowledge. A P-value of less than .05 was considered statistically significant. RESULTS: Out of the 1003 pregnant women, 35.4% (n = 355) were aged 21-25 years, 33.9% (n = 340) had primary education, 73.6% (n = 738) lived in urban areas, 12.2% (n = 122) were smokers, 38.3% (n = 384) reported chewing khat, and the majority (90.2%, n = 905) were unemployed. Also, 65.5% (n = 657) of the participants reported taking folic acid in their current pregnancy. A total of 2,623 medications were utilized during pregnancy, with 17.8% during the first trimester (n = 468). Around 39.3% (n = 1,037) of medications used fell under the blood and blood-forming organs category. Education level (AOR: 4.00, P < .001), insurance status (AOR: 1.71, P = .026), information about medication risks to the fetus (AOR: 1.96, P = .023), the use of folic acid either in a previous pregnancy (AOR: 1.65, P < .008) or in the current pregnancy (AOR: 4.26, P < .001), and checking the medication leaflet (AOR: 5.67, P < .001) were predictors of higher knowledge. CONCLUSION: The findings underscore the pressing need for educational interventions aimed at pregnant women. By bridging knowledge gaps and promoting informed decision-making, such initiatives can contribute to a safer and healthier pregnancy journey, reducing the inclination towards self-medication.

Discovering the strength of immunometabolism in cancer therapy: Employing metabolic pathways to enhance immune responses.

Immunometabolism, which studies cellular metabolism and immune cell function, is a possible cancer treatment. Metabolic pathways regulate immune cell activation, differentiation, and effector functions, crucial to tumor identification and elimination. Immune evasion and tumor growth can result from tumor microenvironment metabolic dysregulation. These metabolic pathways can boost antitumor immunity. This overview discusses immune cell metabolism, including glycolysis, oxidative phosphorylation, amino acid, and lipid metabolism. Amino acid and lipid metabolic manipulations may improve immune cell activity and antitumor immunity. Combination therapy using immunometabolism-based strategies may enhance therapeutic efficacy. The complexity of the metabolic network, biomarker development, challenges, and future approaches are all covered, along with a summary of case studies demonstrating the effectiveness of immunometabolism-based therapy. Metabolomics, stable isotope tracing, single-cell analysis, and computational modeling are also reviewed for immunometabolism research. Personalized and combination treatments are considered. This review adds to immunometabolism expertise and sheds light on metabolic treatments' ability to boost cancer treatment immunological response. Also, in this review, we discussed the immune response in cancer treatment and altering metabolic pathways to increase the immune response against malignancies.

ChatGPT and Clinical Training: Perception, Concerns, and Practice of Pharm-D Students.

Background: The emergence of Chat-Generative Pre-trained Transformer (ChatGPT) by OpenAI has revolutionized AI technology, demonstrating significant potential in healthcare and pharmaceutical education, yet its real-world applicability in clinical training warrants further investigation. Methods: A cross-sectional study was conducted between April and May 2023 to assess PharmD students' perceptions, concerns, and experiences regarding the integration of ChatGPT into clinical pharmacy education. The study utilized a convenient sampling method through online platforms and involved a questionnaire with sections on demographics, perceived benefits, concerns, and experience with ChatGPT. Statistical analysis was performed using SPSS, including descriptive and inferential analyses. Results: The findings of the study involving 211 PharmD students revealed that the majority of participants were male (77.3%), and had prior experience with artificial intelligence (68.2%). Over two-thirds were aware of ChatGPT. Most students (n= 139, 65.9%) perceived potential benefits in using ChatGPT for various clinical tasks, with concerns including over-reliance, accuracy, and ethical considerations. Adoption of ChatGPT in clinical training varied, with some students not using it at all, while others utilized it for tasks like evaluating drug-drug interactions and developing care plans. Previous users tended to have higher perceived benefits and lower concerns, but the differences were not statistically significant. Conclusion: Utilizing ChatGPT in clinical training offers opportunities, but students' lack of trust in it for clinical decisions highlights the need for collaborative human-ChatGPT decision-making. It should complement healthcare professionals' expertise and be used strategically to compensate for human limitations. Further research is essential to optimize ChatGPT's effective integration.

Association between maternal exposure to arsenic by drinking water during pregnancy and risk of preterm birth: a systematic review and meta-analysis.

The relation of exposure to arsenic in drinking water during pregnancy to the risk of preterm birth (PTB) was contradictory. This meta-analysis aimed to examine the association between drinking water arsenic and PTB. A systematic search in PubMed and Scopus was performed to achieve all relevant studies. Odds ratios (OR) and 95% confidence intervals (CI) were used to pool data using the random-effect models. Overall, 11 studies with a total sample size of 3,404,189 participants were included in the meta-analysis. Arsenic exposure through drinking water during pregnancy was related to an increased risk of PTB (OR = 1.06; 95%CI = 1.01-1.10 for highest versus lowest category of arsenic), with significant heterogeneity across the studies (I2 = 84.8%, P = 0.001). This finding was supported by cohort studies (OR = 1.05; 95%CI = 1.01-1.10). This meta-analysis proposes that higher arsenic exposure in drinking water may be a risk factor for PTB.

Targeting autophagy with tamoxifen in breast cancer: From molecular mechanisms to targeted therapy.

BACKGROUND: Tamoxifen (TAM) is often recommended as a first-line treatment for estrogen receptor-positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro-autophagy and autophagy has recently been identified to be altered in BC, which suggests a potential mechanism for TAM resistance. Autophagy is a cellular stress-induced response to preserve cellular homeostasis. Also, therapy-induced autophagy, which is typically cytoprotective and activated in tumor cells, could sometimes be non-protective, cytostatic, or cytotoxic depending on how it is regulated. OBJECTIVE: This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells. METHODS: Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study. RESULTS: The results demonstrated that protein kinases such as pAMPK, BAX, and p-p70S6K could be a sign of autophagy in developing TAM resistance. According to the study's findings, autophagy plays an important role in BC patients' TAM resistance. CONCLUSION: Therefore, by overcoming endocrine resistance in estrogen receptor-positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM.

An in vitro investigation of the apoptosis-inducing activity of corosolic acid in breast cancer cells.

Objectives: Breast cancer is the most prevalent cancer among females with different molecular subtypes. Corosolic acid is a pentacyclic triterpenoid with anti-cancer properties. Materials and Methods: The MTT assay was used to assess the cytotoxic activity of corosolic acid on MDA-MB-231 and MCF7 cell lines. To determine the apoptotic cells, the flow cytometry technique was utilized. The expression levels of apoptosis-related genes and proteins were quantified using quantitative real time-PCR (qRT-PCR) and Western blotting methods. The activity of caspase enzymes was measured by spectrophotometry. Results: Corosolic acid significantly inhibited the proliferation of both cell lines compared with controls. This agent markedly induced apoptosis in MDA-MB-231 cells but did not affect MCF7 cells compared with controls. Treating the MADA-MB-231 and MCF7 cell lines with corosolic acid showed an inducing effect on apoptosis-associated caspases, including Caspase-8, 9, and -3, in MADA-MB-231 cells with no effect on apoptotic markers in MCF7 cells. Further experiments uncovered corosolic acid-induced apoptosis in MADA-MB-231 cells by decreasing the expression of the phosphorylated form of JAK2 and STAT3 proteins. Conclusion: The present data suggested that corosolic acid is an apoptosis-inducing phytochemical in triple-negative breast cancer MADA-MB-231 cells. Also, corosolic acid triggered apoptosis in these cells by stimulating both pathways of apoptosis and inhibiting the JAK/STAT signaling. Furthermore, corosolic acid was found to inhibit MCF7 cell proliferation by a non-apoptotic mechanism.

Overview of the role and action mechanism of microRNA-128 in viral infections.

Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.

Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism.

MicroRNAs (miRNAs) are emerging as a significant modulator of immunity, and their abnormal expression/activity has been linked to numerous human disorders, such as cancer. It is now known that miRNAs potentially modulate the production of several metabolic processes in tumor-associated immune cells and indirectly via different metabolic enzymes that affect tumor-associated signaling cascades. For instance, Let-7 has been identified as a crucial modulator for the long-lasting survival of CD8+ T cells (naive phenotypes) in cancer by altering their metabolism. Furthermore, in T cells, it has been found that enhancer of zeste homolog 2 (EZH2) expression is controlled via glycolytic metabolism through miRNAs in patients with ovarian cancer. On the other hand, immunometabolism has shown us that cellular metabolic reactions and processes not only generate ATP and biosynthetic intermediates but also modulate the immune system and inflammatory processes. Based on recent studies, new and encouraging approaches to cancer involving the modification of miRNAs in immune cell metabolism are currently being investigated, providing insight into promising targets for therapeutic strategies based on the pivotal role of immunometabolism in cancer. Throughout this overview, we explore and describe the significance of miRNAs in cancer and immune cell metabolism.