Synthesis, characterization, and evaluation of antibacterial and antifungal activities of CuO-ZnO-Co3O4 nanocomposites.

The co-precipitation method was used to prepare CuO, ZnO, Co3O4 nanoparticles and CuO-ZnO-Co3O4 nanocomposite. The structural, morphological, and optical properties of the prepared samples were studied using X-ray diffraction (XRD), total reflection X-ray fluorescence (TXRF), transmission electron microscopy (TEM), selected area electron diffraction (SAED), diffuse reflectance spectroscopy (DRS), and zeta potential. XRD analysis revealed that the crystal structures of CuO, ZnO, and Co3O4 nanoparticles are monoclinic, hexagonal, and cubic, with average crystallite sizes of 30.8 nm, 31.8 nm, and 32.8 nm, respectively. For CuO-ZnO-Co3O4 nanocomposites, the corresponding sizes were 24.9 nm, 13.6 nm, and 16.1 nm. The optical bandgaps of CuO, ZnO, Co3O4 nanoparticles, and CuO-ZnO-Co3O4 nanocomposites were 1.5 eV, 3.14 eV, 1.2 eV, and 1.3 eV, respectively. In this study, the antibacterial activity of CuO-ZnO-Co3O4 nanocomposite against Gram-negative bacteria (E. coli, Klebsiella, pseudomonas, and Salmonella) and Gram-positive bacteria (Staphylococcus aureus) was investigated and compared with the antibiotic Azithromycin. In addition, the effect of the nanocomposite on fungi was studied and compared with the antifungal Mystatin.

Unveiling the potency of FDA-approved oxidopamine HBr for cervical cancer regulation and replication proteins.

Cervical Cancer remains a women's health concern worldwide and ranks among the most prevalent cancers, particularly in developing countries. Many women are diagnosed with cervical cancer, with a substantial number succumbing to the disease even after the availability of vaccines and drugs. The tumour microenvironment often exhibits immune evasion, including suppression of T-cell activity and altered cytokine, impacting the efficacy of therapeutic interventions and highlighting the need for treatments to modulate the immune response. Despite efforts to promote HPV vaccination and regular screenings, it causes many deaths, underscoring the urgent need for continued research, healthcare access, and rapid drug development or repurposing. In this study, we identified various proteins involved in cervical cancer cell cycle regulation and DNA replication proteins, performed the multitargeted docking with an FDA-approved library, and identified Oxidopamine HBr as a multitargeted drug. Studies extended with pharmacokinetics and compared with the standard values followed by DFT, which supported the compound as a multitargeted inhibitor. Further, the docked complexes were taken for the interaction fingerprints, and it was identified that there are many 9 polar, 5 hydrophobic, 2 aromatic, and 2 basic residues. We extended our studies for 100ns MD Simulation in water, and the computations explored the deviation and fluctuations under 2Å and many intermolecular interactions; the same trajectory files were used for the MM\GBSA studies. All the studies have supported the Oxidopamine HBr as a cervical cancer multitargeted inhibitor-however, experimental studies are needed before human use.

Phytochemical Composition and Bioactivities of Some Hydrophytes: Antioxidant, Antiparasitic, Antibacterial, and Anticancer Properties and Mechanisms.

Few researches have explored the production of pharmaceuticals from aquatic plants. Therefore, this study explored, for the first time, the phytochemical composition and bioactivities of ten aquatic plants. Aquatic plant shoots from various Nile River canals were collected, dried, and ground for aqueous extract preparation. Phytochemical composition and antioxidant capacity were assessed using DPPH assays. Extracts were tested for antiparasitic, antibacterial, anti-biofilm, and anticancer activities through standard in vitro assays, measuring IC50 values, and evaluating mechanisms of action, including cell viability and high-content screening assays. The results showed that the aquatic plants were rich in pharmaceutical compounds. The antioxidant capacity of these extracts exceeded that of vitamin C. The extracts showed promising antiparasitic activity against pathogens like Opisthorchis viverrini and Plasmodium falciparum, with IC50 values between 0.7 and 2.5 µg/mL. They also demonstrated low MICs against various pathogenic bacteria, causing DNA damage, increased plasma membrane permeability, and 90% biofilm inhibition. In terms of anticancer activity, extracts were effective against a panel of cancer cell lines, with Ludwigia stolonifera exhibiting the highest efficacy. Its IC50 ranged from 0.5 µg/mL for pancreatic, esophageal, and colon cancer cells to 1.5 µg/mL for gastric cancer cells. Overall, IC50 values for all extracts were below 6 µg/mL, showing significant apoptotic activity, increased nuclear intensity, plasma membrane permeability, mitochondrial membrane permeability, and cytochrome c release, and outperforming doxorubicin. This study highlights the potential of aquatic plants as sources for new, safe, and effective drugs with strong antiparasitic, antibacterial, and anticancer properties.

Correction: Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

Assessment of community pharmacists' knowledge, attitudes and their willingness to provide vaccination services in Saudi Arabia.

BACKGROUND: Community pharmacists play an important role in increasing vaccination rates especially in countries where they offer vaccination services and administration. However, little is known about community pharmacist's willingness to provide vaccination services in Saudi Arabia. The objective of this study was to assess knowledge, attitudes, willingness and beliefs of community pharmacists in Saudi Arabia towards providing vaccines at pharmacies. METHODS: A cross-sectional, online questionnaire-based study using convenience sampling (Snowball technique) was used to obtain responses from community pharmacists across Saudi Arabia. The survey collected information on participants' demographics, knowledge about vaccine, attitude towards vaccine and their attitude to be immunization providers. Bivariate analysis and multiple linear regression models were employed to assess the relationships between demographic variables and outcomes. RESULTS: The study sample consisted of 384 community pharmacists. More than half of participants had poor knowledge about vaccines (54%). Only 8.4% of participants had good knowledge about vaccines. The results indicated that community pharmacists in the study sample have positive attitude toward vaccines and are willing to provide vaccination services. There was a significant relationship between knowledge about vaccine and attitude toward vaccines. Pharmacists with poor knowledge about vaccines had negative attitude toward vaccines as compared to those with high knowledge (ß = -1.743; P-value = 0.024). Additionally, there was a significant relationship between knowledge about vaccine and attitude to be immunization providers. Pharmacists with poor knowledge about vaccines had negative attitude to be immunization providers as compared to those with high knowledge (ß = -2.631; P-value = 0.002). Furthermore, a significant number of the community pharmacists reported facing critical barriers to provide vaccines including legal liability, lack of personal resources and lack of appropriate training. CONCLUSION: Comprehensive training and certification programs for pharmacists are crucial to improve their competencies in handling and administering vaccines to increase the rate of vaccinations in Saudi Arabia.

Khat chewing among parents and their children: A potential transgenerational effect.

Background: Khat has a stimulating and addictive effect and can induce consequences on the health and socioeconomic status of khat chewers. Objectives: This study aims to assess knowledge, attitude, and practice of khat chewing among parents in Jazan and its consequential effect on their children. Methods: This cross-sectional investigation was conducted in the Jazan region of Saudi Arabia. Data was collected via a web-based, self-administered questionnaire measuring demographics, knowledge, attitudes, and practices concerning khat chewing. The Chi-square test or Fisher's exact test was used to assess factors associated with khat chewing among parents and its consequential effect on their children. Results: A total of 724 parents were included. The sample had an overall good knowledge about the health hazards of khat chewing and an attitude against khat chewing. Nonetheless, the number of parents who reported that they had ever tried khat chewing was 200 (27.6%) and 106 parents (14.6%) confirmed that their children were khat chewers. Additionally, 98 (13.5%) parents declared that they practiced khat chewing in front of their children. Higher frequencies of parents who reported providing khat to their children were identified among parents with higher attitude levels that favor khat chewing (P value = 0.04). Conclusions: Efforts should be made to develop targeted preventive and educational strategies to reduce khat chewing among parents who have favorable attitudes toward khat chewing.

The Knowledge, Attitudes, and Practices of Primary Healthcare Physicians in the Al Qassim Region, Saudi Arabia Regarding Travel Medicine: A Cross-Sectional Study.

Background and objective In the age of globalization, diseases associated with travel have emerged as a focal point of public health interest. This has become particularly relevant in Saudi Arabia after the changes in tourism policy in recent years. Primary care physicians are expected to suspect diseases of importance in certain geographic areas. They should dispense pre- and post-travel advice. This study aimed to assess the knowledge, attitudes, and practices of primary care physicians in the Al Qassim region, Saudi Arabia regarding travel medicine. Methods This cross-sectional study was conducted in the Al Qassim region, Saudi Arabia between October and November 2023. We reached out to all primary care physicians in the region regardless of their gender, nationality, and years of experience. The data were collected using a self-administered questionnaire, which was designed based on the available literature and validated by experts. Results A total of 197 physicians participated in the study; 74% were male, 46% were general practitioners, and 48% had 5-10 years of experience. More than half (51%) of the participants reported a weekly patient load of 50-100, while 47% engaged with 5-10 travelers annually; 53% provided travel health advice and a quarter of primary healthcare physicians never attended travel update sessions or conferences. In the last six months, 48% and 43% of the physicians conducted pre- and post-travel consultations respectively. Approximately 49.2% demonstrated a fair knowledge of the topic. Factors associated with fair knowledge included non-Saudi nationality, age below 30 years, minimal traveler exposure, and infrequent conference attendance (p<0.05). A positive attitude was linked to being under 30 years old, having <5 years of experience, seeing <5 travelers yearly, and possessing a fair knowledge of the topic (p<0.05). Conclusions Overall, about half of the physicians in the Al Qassim region engage with travelers and demonstrate good attitudes and practices toward travel medicine. Opening Saudi borders to tourism necessitates the inclusion of travel medicine in continuing medical education programs to prepare primary care physicians to care for travelers more efficiently.

Epigenetic changes in shear-stressed endothelial cells.

Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions.

Myeloablative Haploidentical Donor Hematopoietic Transplantation Using Post-Transplantation Cyclophosphamide and Antithymocyte Globulin.

Haploidentical donor (haplo-) hematopoietic stem cell transplantation (HSCT) with post-transplantation cyclophosphamide (PTCy) is now performed on a large scale worldwide. Our patient outcomes did not completely reflect the results published by other groups. We herein present the results of 60 patients with hematologic malignancies treated homogeneously on a modified version of the standard protocol by adding ATG as an additional graft-versus-host disease (GVHD) prophylaxis measure. This was a retrospective analysis of 60 haplo-HSCT recipients using a myeloablative conditioning regimen with antithymocyte globulin and PTCy for GVHD prophylaxis. At 5 years, overall survival was 59.2%, relapse-free survival (RFS) was 48.6%, and chronic GVHD (cGVHD) and relapse-free survival was 40%. The median time to neutrophil and platelet engraftment was 16 days and 28.5 days, respectively. The rates of grade II-IV acute GVHD and extensive cGVHD were 46.7% and 23.3%, respectively. The cumulative incidence of relapse was 30%, nonrelapse mortality was 21.6%, and transplantation-related mortality was 11%. Higher Disease Risk Index and 50% HLA match were associated with lower RFS. Female donor to male recipient and older donor age were associated with an elevated risk of cGVHD. The use of PTCy might not yield the same results in different populations. Many remaining questions need to be addressed in randomized trials, including optimal graft source and donor, date of calcineurin inhibitor initiation, personalized or targeted dose of PTCy, immune reconstitution, and others.

Retraction: Intussusception in Adults: A Rare Etiology of Small Intestinal Obstruction.

[This retracts the article DOI: 10.7759/cureus.20502.].

Retraction: Urinary Bladder Hernia: A Rare Cause of Urinary Frequency.

[This retracts the article DOI: 10.7759/cureus.20993.].

Retraction: Lipoma of the Pancreas: A Rare Incidental Tumor.

[This retracts the article DOI: 10.7759/cureus.20122.].

Retraction: Large Pleural Lipoma Manifesting With Chronic Shoulder Pain.

[This retracts the article DOI: 10.7759/cureus.21113.].

Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

The Impact of Negative Emotions on Binge Eating and BMI Among Medical Students.

Background Binge eating disorder (BED) is a condition characterized by episodes of consuming large amounts of food and feeling a lack of control over eating behavior. Stress, anxiety, and depression are risk factors for developing BED, which may be particularly relevant for medical students who experience high levels of academic pressure and stress. This study aims to investigate the prevalence of binge eating behaviors among medical students, as well as the types of negative emotions that are most strongly associated with binge eating. Methodology This cross-sectional study employed convenience sampling and included 332 medical students from Almaarefa University in Riyadh, Saudi Arabia. All medical students of all academic levels were eligible to participate in this study. Students from other colleges such as pharmacy students or students from other universities were excluded from this study. The research questionnaire collected information about negative emotions, BMI, number of meals, consumption of fast food, overeating behavior, and relevant demographic data. Descriptive and inferential statistics were used to analyze the data using SPSS Statistics version 26 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.). Results The descriptive analysis showed that the majority of students reported consuming two meals per day and having snacks twice a day. Fast food consumption was reported by 58.1% of students. The study found that negative emotions such as stress, depression, and loneliness were significantly associated with binge eating behavior and had an impact on weight and BMI. The findings suggest the need for interventions to address negative emotions and promote healthy eating habits among medical students. Conclusion The study concludes that negative emotions such as stress, aggression, and boredom are significantly associated with binge eating behaviors among medical students. Depression, disappointment, and thoughts about difficult tasks were linked to detrimental effects on BMI and weight loss.

Incidence and risk factors for secondary graft failure in uniformly treated patients with severe aplastic anemia receiving fludarabine and cyclophosphamide for conditioning and matched sibling bone marrow graft as stem cell source.

BACKGROUND AIMS: Graft failure after allogeneic transplant for aplastic anemia is problematic. The risk of graft failure depends on multiple variables, including the preparative regimen, donor type, stem cell dose and source among other variables. METHODS: We performed a retrospective analysis of patients with aplastic anemia who underwent matched-sibling allogeneic transplant at a single center. RESULTS: We identified 82 patients who fit the inclusion criteria. One had primary graft failure and was excluded from this analysis. The recipient median age was 22 years. The donor median age was 23 years. The median time from diagnosis to transplant was 1.6 months. The median number of red cell transfusions before transplant was nine. The median number of platelet transfusions before transplant was 18. Thirteen patients developed secondary graft failure, with a cumulative incidence at 5 years of 16% and median time to develop secondary graft failure of 129 days. All patients engrafted with a median time for neutrophil engraftment of 19 days and a median time for platelet engraftment of 22 days. The survival of patients with or without secondary graft failure was not different. Major or bidirectional ABO incompatibility and older recipient age were statistically significantly associated with greater risk of secondary graft failure. CONCLUSIONS: Secondary graft failure is a significant complication after allogeneic transplant for SAA. Identification of recipients at risk and mitigating the potential risks of this complication is warranted.

Surgical androgen deprivation therapy in advanced prostate cancer in patients of African descent: comparison of biochemical efficacy of bilateral total and subcapsular orchidectomy.

Background: Surgical androgen deprivation therapy (ADT) to treat advanced prostate cancer can be achieved either by bilateral total orchidectomy (BTO) or bilateral subcapsular orchidectomy (BSCO). However, biochemical and clinical equivalence between BTO and BSCO among native Africans is undocumented. Objective: To compare the biochemical response (testosterone and prostate specific antigen) in patients who had BTO and BSCO for advanced prostate cancer. Methods: A randomized single- blind study of 64 consenting patients that underwent either BTO or BSCO. Pre- and post-operative PSA and testosterone assays were done serially at intervals and compared between each treatment group. Results: Each treatment group were similar with no statistically significant difference in terms of age (p= 0.449) or degree of tumor differentiation (p =0.714). Neither median testosterone (p= 0.515) nor the mean pre-operative PSA differ between the two groups (p = 0.482). Also, similar trends were noticed post operatively except at the 2nd month when a statistically significant difference was recorded (p = 0.003). Conclusion: The two techniques of orchidectomy were effective in accomplishing androgen deprivation. They produced similar biochemical (testosterone and PSA) response.

Forced Swimming-Induced Depressive-like Behavior and Anxiety Are Reduced by Chlorpheniramine via Suppression of Oxidative and Inflammatory Mediators and Activating the Nrf2-BDNF Signaling Pathway.

The first-generation antihistamine chlorpheniramine (CPA) is believed to have both anxiolytic and antidepressant properties. The current study sought to assess the mechanisms behind the antidepressant and anxiolytic effects of CPA therapy concerning oxidative stress, inflammation, and nuclear factor p45 for erythroid 2-Brain-derived neurotrophic factor (Nrf2-BDNF) signaling pathway in forced swimming-induced depressive-like behavior and anxiety. Eighteen male Wistar rats (180-200 gm) rats were separated into three groups (n = 6): a stressed group (acute stress) that underwent the forced swimming test (FST) and a stressed group that received pretreatment with CPA (10 mg/kg body weight) for 3 weeks (CPA + acute stress). Animals were subsequently put through the following behavioral tests after undergoing a forced swim test (FST) for 5 min: an immobility test, open field test, and elevated plus maze test. Serum cortisol levels were measured when the rats were euthanized at the end of the experiments. Brain neurotransmitters (cortisol, serotonin, and noradrenaline), oxidative stress (SOD and MDA), inflammatory (IL-6 and IL-1) biomarkers, and the Nrf2-BDNF signaling pathway in the hippocampus and cerebral cortex tissues was determined. CPA prevented stress-induced increases in cortisol levels (p < 0.0001), decreased brain neurotransmitters, and increased oxidative stress and inflammation. CPA also upregulated the Nrf2-BDNF signaling pathway. Thus, CPA mitigates depressive-like behavior and anxiety by inhibiting oxidative stress and inflammation and upregulating the Nrf2-BDNF signaling pathway in the brain tissues.

Successful restoration of checkpoint inhibitors efficacy after allogeneic hematopoietic cell transplant for classic Hodgkin lymphoma patients.

BACKGROUND: Classic Hodgkin lymphoma (cHL) is a highly-curable disease. However, relapses after bone marrow transplant are challenging especially relapses after allogeneic transplant. METHODS: A retrospective chart review of the institution transplant database to summarize the safety and efficacy of checkpoint inhibitors (CPIs) use for cHL relapses postallo-HCT in patients who already failed to derive sustained benefit from CPIs received prior to allo-HCT. RESULTS: Six cases were identified and reviewed. All patients received and failed to derive sustained benefit from CPIs and brentuximab vedotin preallo-HCT. The median age at the time of allo-HCT was 28.6 years (IQR 23.6-34.2), the median number of lines received prior to allo-HCT was 6.5 (range 5-9). The median duration of CPI therapy prior to allo-HCT was 8.1 months (IQR 6.7-12.9). The median time between the discontinuation of CPI and allo-HCT was 5.78 months (IQR 3.15-15.8). The median time to progression postallo-HCT was 5.75 months (IQR 2.6-11.7). The median time between allo-HCT and re-challenge with a CPI was 7.6 months (IQR 3.2-28.6). The median time of follow up after starting postallo-HCT CPIs was 16 months (IQR 7.25-25.75). Five out six patients responded and two patients developed GvHD. CONCLUSION: Our report shows preserved efficacy without any new safety signals by using CPIs postallo-HCT despite using and having failed to derive sustained benefit from CPIs preallo-HCT.

Corrigendum: Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

[This corrects the article DOI: 10.3389/fvets.2023.1089733.].