Through the ACE2, a main enzyme of the renin–angiotensin system (RAS), SARS-CoV-2 gains access into the cell, resulting in different complications which may extend beyond the RAS and impact the Arachidonic Acid (ArA) pathway. The contribution of the RAS through ArA pathways metabolites in the pathogenesis of COVID-19 is unknown. We investigated whether RAS components and ArA metabolites can be considered biomarkers of COVID-19. We measured the plasma levels of RAS and ArA metabolites using an LC-MS/MS. Results indicate that Ang 1–7 levels were significantly lower, whereas Ang II levels were higher in the COVID-19 patients than in healthy control individuals. The ratio of Ang 1–7/Ang II as an indicator of the RAS classical and protective arms balance was dramatically lower in COVID-19 patients. There was no significant increase in inflammatory 19-HETE and 20-HETE levels. The concentration of EETs was significantly increased in COVID-19 patients, whereas the DHETs concentration was repressed. Their plasma levels were correlated with Ang II concentration in COVID-19 patients. In conclusion, evaluating the RAS and ArA pathway biomarkers could provide helpful information for the early detection of high-risk groups, avoid delayed medical attention, facilitate resource allocation, and improve patient clinical outcomes to prevent long COVID incidence.

Perinatal mental health is a major public health issue that arises during pregnancy and/or after birth, with substantial implications for social, parental, and maternal functioning, as well as overall quality of life. The study aimed to determine the prevalence of perinatal depression and its associated risk factors among women who visited a maternity hospital in Kathmandu, Nepal. A cross-sectional study was conducted at the Paropakar Maternity and Women’s Hospital in Kathmandu. A total of 300 women in their perinatal period were interviewed. The Edinburgh Perinatal Depression Scale (EPDS) was used to measure perinatal depression. The Poisson regression model was used to determine risk factors associated with perinatal depression. The mean age of respondents was 25.5 (SD 4.5) years; average age during their first pregnancy was 23.5 (SD 3.7) years; and 53.7% of respondents were in the antenatal period. The prevalence of depressive symptoms (EPDS ≥ 10) was 40% (95% CI 31.4% to 45.8%). Unsupportive family members (adjusted prevalence ratio [aPR] 2.23; 95% CI 1.75–2.86), postnatal period (aPR 2.64; 95% CI 1.97–3.53), complications faced during delivery (aPR 1.76; 95%CI 1.30–2.39), history of intimate partner violence (aPR 0.48; 95% CI 0.36–0.64), and first pregnancy at the age of ≤25 years (aPR 0.61; 95% CI 0.42–0.88) were identified as key risk factors of perinatal depression. Strong family support and the active involvement of partners in counselling can contribute to alleviating perinatal depression symptoms. Targeted interventions in health and well-being services should be implemented to address mental health burden during both pregnancy and postpartum periods.

Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 factorial randomized, controlled design wherein healthy men and women (n = 32) consumed either a grape or placebo drink with a high-fat meal in the morning or evening. Urine was collected for measurements of biomarkers of oxidative stress and grape metabolites at baseline and post-meal at hour 1 and hours 1–6. F-2 isoprostane levels showed main effects of time period (baseline < hour 1 < hours 1–6, p < 0.0001), time (a.m. > p.m., p = 0.008) and treatment (placebo > grape, p = 0.05). Total F2-isoprostane excretion expressed as % baseline was higher in the a.m. vs. p.m. (p = 0.004) and in the a.m. placebo vs. all other groups (p < 0.05). Tartaric acid and resveratrol excretion levels were higher in the grape vs. placebo group (p < 0.05) but were not correlated with F-2 isoprostane levels. The findings support a protective effect of grape consumption against morning sensitivity to oxidative stress.

Nicotinic acetylcholine receptors (nAChRs) are membrane-bound proteins that mediate fast synaptic transmission throughout the nervous system. A functional nAChR subtype is formed by the combination of multiple subunits arranged as homomeric or heteromeric pentamers, each with a distinct pharmacological profile. Disruption of their neurotransmission contributes to various neuropathologies, emphasizing the need for detailed knowledge of receptor structure, function, subunit composition, dynamics, and potential ligand-binding sites. However, their structural complexity as integral membrane proteins has hindered expression in mammalian cell lines and proven even more challenging to crystallize, limiting insights into ligand interactions. Understanding the molecular determinants governing nAChRs function is essential for the rational design of selective therapeutics targeting neurological disorders. The emergence of a chimeric receptor approach has dramatically improved the ability to study these important proteins and opened new avenues for high-throughput screening in drug discovery efforts. This review explains how the design of chimera constructs using soluble homologs, such as AChBP, provides researchers with an immense opportunity to investigate receptor structure–function relationships and subtype-specific properties, thereby facilitating the development of more effective treatments.

Jaspine B, an anhyrophytosphingosine, has potent anticancer properties. However, it exhibits low oral bioavailability, reducing therapeutic effects despite its cytotoxicity. This study aimed to address this issue by improving the pharmacokinetics of Jaspine B through liposomal formulation. Jaspine B liposomes were prepared using microfluidic techniques and characterized using transmission electron microscopy (TEM). A sensitive and selective LC-MS/MS method was developed and validated to quantify Jaspine B concentrations in the rat plasma. The analytical method showed linearity in a wide range of concentrations with high precision. Sprague Dawley rats were used to carry out a pharmacokinetic study to assess the impact of liposomal formulation on the pharmacokinetic parameters of Jaspine B. The liposomal formulation successfully improved the PK of the drug with enhanced bioavailability, increased half-life, and circulation time in the plasma, leading to improved therapeutic outcomes.

Background/Objectives: Jaspine B, a synthetic analog of anhydrophytosphingosine, demonstrates significant anticancer activity; however, its clinical application is hindered by its poor oral bioavailability, resulting in suboptimal systemic exposure. This study aimed to enhance the pharmacokinetic properties of Jaspine B by developing a liposomal delivery system. Methods: Jaspine B-loaded liposomes were formulated using a microfluidic approach and characterized by transmission electron microscopy (TEM) to assess particle morphology and size distribution. A sensitive and selective LC-MS/MS assay was developed and fully validated to quantify Jaspine B in rat plasma. The assay revealed excellent linearity across a broad concentration range and high intra- and inter-day precision. A pharmacokinetic study was conducted in Sprague Dawley rats to evaluate the influence of liposomal encapsulation on the pharmacokinetic profile of Jaspine B. Results: The liposomal formulation accelerated the absorption of Jaspine B, reaching the maximum concentration (T_max) at 2 h as opposed to 6 h in plain Jaspine B. The half-life (t_1/2) increased significantly from 7.9 ± 2.3 h to 26.7 ± 7.3 h. The area under the curve (AUC_0–∞) increased over two-fold from 56.8 ± 12.3 ng.h/mL to 139.7 ± 27.2 ng.h/mL, suggesting increased systemic drug exposure. Similarly, the drug molecule’s mean residence time (MRT) increased over three-fold. Conclusions: These results indicate that liposomal formulation enhances the pharmacokinetics of Jaspine B, prolonging its body circulation and exposure, which explains the improved therapeutic outcomes we observed in our previous pharmacodynamic study.