Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies.

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/− 0.4% for methylisothiazolinone and C +/− 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R² of 0.9996.

A good understanding of the possible risk factors for coronavirus disease 19 (COVID-19) severity could help clinicians in identifying patients who need prioritized treatment to prevent disease progression and adverse outcomes. COVID-19-linked coagulopathy is one of the life-threatening severe acute respiratory syndrome coronavirus 2 infections. Growing evidence indicates a correlation between abnormal coagulation and increased risk of venous thromboembolism; in COVID-19-infected patients, yet a clear understanding of the role of coagulopathy in the severity of COVID-19 illness is still unresolved. This retrospective cohort study was thus undertaken to investigate the role of coagulation dysfunction with COVID-19 mortality/severity. Blood samples from 1000 hospitalized patients with COVID-19 pneumonia were collected. The study participants were both male and female in equal ratios with a mean age of 48.94. Patients were followed-up until discharge either for recovery or death. All biochemical investigations-complete blood count and coagulation profile including D-dimers, prothrombin time, partial prothrombin time, and international normalized ratio was performed in COVID-19 survivors and in non-survivors admitted in intensive care unit. In the survivor group, all coagulation parameters were within normal limits, and 8.7% had a low red blood count. The most common risk factors associated with COVID-19 patients were diabetes mellitus (2.8%), hypertension (10.8%), and heart disease (3%). In the non-survivor group, the coagulation parameters were above the normal range (prothrombin in 31.5%, PTT in 10.5%, international normalized ratio in 26.3%, D-dimer in 36.8%) with thrombocytopenia in 21.04% of patients. Other complications were pulmonary embolism in 21.05% and venous thromboembolism in 15.7% of non-survivors. A significant association was found between increased markers of coagulopathy and the severity of SARS-CoV2 infection. Furthermore, the severity of infection was observed to increase with risk factors such as age, heart disease, hypertension, and DM eventually affecting COVID-19 prognosis and mortality.

Neuroinflammation via the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway and reduced hippocampal brain-derived neurotrophic factor (BDNF) expression are key mechanisms underlying stress-induced depression. Vitamin D3, acting through the vitamin D receptor (VDR), is known to possess immunomodulatory and neurotrophic properties, but its role under chronic stress remains unclear. This study investigated the effects of vitamin D3 on chronic unpredictable mild stress (CUMS)-induced neuroinflammation and neurotrophic deficits in male Wistar rats. Thirty-two rats were divided into four groups: control, CUMS only, CUMS + vitamin D3 (1000 IU/kg), and CUMS + vitamin D3 (10,000 IU/kg). Vitamin D3 was injected intramuscularly three times weekly for 28 days. Hippocampal mRNA expression of cGAS–STING pathway markers, BDNF, microglial activation marker Iba1, and pro-inflammatory cytokines was quantified by RT-qPCR, and relative expression was calculated using the 2^−ΔΔCt method. Serum vitamin D3 and corticosterone concentrations were measured by ELISA. CUMS significantly reduced serum vitamin D3, increased corticosterone, activated hippocampal cGAS–STING signaling, upregulated inflammatory mediators and Iba1, and suppressed VDR and BDNF mRNA expression (all p < 0.05). Vitamin D3 administration effectively restored serum vitamin D3, normalized corticosterone levels, attenuated cGAS–STING activation and inflammatory gene expression, reduced microglial activation, and enhanced hippocampal VDR and BDNF mRNA expression (all p < 0.05). These findings demonstrate that vitamin D3 alleviates CUMS-induced hippocampal inflammation and neurotrophic deficits through coordinated modulation of immune signaling and BDNF, highlighting its potential as a therapeutic approach for stress-related brain disorders.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs (S-Allyl Cysteine Poly (D,L-lactide-co-glycolic acid) Nanoparticles) were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency to be 5.13 ± 0.10% and 82.36 ± 4.01%, respectively. SC PLGA NPs showed a spherical morphology of an average size (134.8 ± 4.61 nm), PDI: 0.277 ± 0.004, and −25.3 ± 1.03 mV Zeta-Potential (ZP), and is suitable for oral delivery. The development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameter examinations with 1.219 min RT, MS (162.00/73.10), and a total run-time of 2.0 min. Additionally, 1.0–1000.0 ng/mL was a linear range with inter- and intra-day accuracy of 92.55–99.40%, followed by a precision of 1.88–4.23%. SC PLGA NP’s oral bioavailability was significantly higher (** p < 0.01) in comparison to the SC-S treated groups’ (iv and oral). The antimicrobial activity of SC PLGA NPs proved to be more effective than pure S-Allyl-L-Cysteine with significant results (p < 0.01) in comparison to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties, which can be helpful for oral administration. Based on the proposed research results, SC PLGA NPs were used for the improvement in oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.