NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model.

Schizophrenia, a global mental health disorder affecting approximately 1 % of the population, is characterized by neurotransmitter dysregulation, particularly dopamine, serotonin, and glutamate. Current antipsychotic therapies, despite their efficacy, are accompanied by adverse effects, which has motivated researchers to investigate more secure substitutes. This study examines the potential antipsychotic effects of esculetin, a natural coumarin derivative recognized for its wide-ranging pharmacological activities (anti-inflammatory, antioxidant, anti-pathogenic, anticancer, and neuroprotective), in animal model of schizophrenia induced by ketamine. In order to induce disease, acute and chronic ketamine administration was performed on Swiss albino mice, supplemented with esculetin (as the test substance) and clozapine (as the reference standard). Behavioral studies and biochemical assays were performed to evaluate positive, negative, and cognitive symptoms of schizophrenia, as well as antioxidant and oxidant levels in various brain regions. Esculetin demonstrated significant improvements in behavioral symptoms, attenuated oxidative stress and neuroinflammation, and modulated neurotransmitter levels. Afterwards, ELISA was performed to evaluate levels of schizophrenia biomarkers AChE, BDNF. Moreover, proinflammatory cytokines (IL-6 and TNF-α) and NF-κB were also determined. Histopathological parameters of under study brain parts i.e., hippocampus, cortex and striata were also assessed. Esculetin and clozapine significantly (***p < 0.0001) altered ketamine induced behavioral symptoms and attenuated ketamine induced oxidative stress and neuroinflammation. Additionally, esculetin significantly (***p < 0.0001) altered neurotransmitter (dopamine, serotonin, glutamate) levels. ELISA analysis depicts ketamine reduced BDNF levels in hippocampus, cortex and striata while esculetin significantly (***p < 0.0001) increased BDNF levels in under study three parts of brain. Histopathological changes were seen in test groups. The findings of this study indicate that esculetin may have therapeutic potential in the treatment of schizophrenia induced by ketamine. As a result, esculetin may have the potential to be utilized as a treatment for schizophrenia.

Efficacy of Remdesivir on Clinical Outcomes in COVID-19 Patients: A Study in a Tertiary Care Hospital in Pakistan.

Background: As of October 3, 2023, the global COVID-19 case tally exceeded 696 million, with almost 7 million fatalities. Remdesivir, approved for treatment of COVID-19 by regulatory bodies, has seen varying recommendations by the World Health Organization over time. Despite certain studies questioning its efficacy, others highlight potential benefits. The objective of this study was to gauge the impact of remdesivir on clinical outcomes in a Pakistani tertiary care hospital. Methods: An analytical cross-sectional study was conducted on 108 COVID-19 patients at Mayo Hospital Lahore between September 2020 and August 2021. Of these, 52 received remdesivir. The study employed a structured proforma for data collection, with analyses conducted using SPSS version 26, considering a p-value of less than 0.05 as statistically significant. Results: Demographic distribution between remdesivir-treated and untreated groups was similar. Significant improvement was observed in the remdesivir cohort in terms of oxygen saturation (58%), ferritin levels (58.2%), chest X-ray results (67.8%), and discharge rates (66.7%) when compared to the untreated group. Stratification based on disease severity showed that remdesivir was particularly beneficial for moderate illness cases in several parameters. Conclusion: This study suggests that remdesivir can be associated with improved outcomes, especially in patients with moderate COVID-19 severity. The data emphasizes the importance of the disease stage when considering therapeutic interventions and calls for more region-specific research to guide health responses amid diverse epidemiological landscapes.

Pharmacological screening of silibinin for antischizophrenic activity along with its acute toxicity evaluation in experimental animals.

Silibinin (SIL), a flavolignan extracted from the medicinal plant "silybum marianum (milk thistle)", has traditionally been used to treat liver disease. This phytochemical has displayed neuroprotective properties, its activity against schizophrenia is not elucidated. The present study was designed to evaluate the antipsychotic potential of silibinin and probe its toxic potential. The acute oral toxicity study was assessed as per OECD 425 guidelines. Animals were divided into two groups of female rats (n = 6): one group served as the normal control and the other group received a 2,000 mg/kg dose of SIL. We also evaluated the antipsychotic potential of SIL. To this end, animals were divided into six groups (n = 10) of mice for both the preventive and curative protocols. Group I (CMC 1 mL/kg) served as the normal control and received CMC 1 mL/kg; group II was the diseased group treated with ketamine (10 mg/kg) i.p; group III was the standard group treated with clozapine 1 mg/kg; groups IV, V, and VI served as the treatment groups, receiving SIL 50, 100, and 200 mg/kg, respectively, orally for both protocols. Improvement in positive symptoms of the disease was evaluated by stereotypy and hyperlocomotion, while negative symptoms (behavioral despair) were determined by a forced swim test and a tail suspension test in the mice models. The results suggested that the LD50 of SIL was greater than 2,000 mg/kg. Moreover, SIL prevented and reversed ketamine-induced increase in stereotypy (p < 0.001) and behavioral despair in the forced swim and tail suspension tests (p < 0.001). Taken together, the findings suggest that silibinin is a safe drug with low toxicity which demonstrates significant antipsychotic activity against the positive and negative symptoms of schizophrenia.

Design, synthesis, and comparative study of optoelectronic properties of arylated triazine-based sulfanilamide derivatives through Suzuki-Miyaura cross-coupling reactions.

In this study, a series of arylated triazine-based sulfanilamide derivatives was designed and synthesized via palladium (Pd-0)-catalyzed, Suzuki-Miyaura cross-coupling. The theoretical investigation of the optoelectronic attributes of the synthesized compounds was accomplished using Gaussian-09 package by Density Functional Theory (DFT) approach at WB97XD/6-31G (d, p). The triazine core was stabilized by the electron-rich environment around the HOMO orbital which in turn ensured the availibity of electrons for complexation of the Pd center. The computations in DFT were carried out for better comprehension of structure-property relationship. The theoretically computed values were in good agreement with the experimental findings. The outcomes of this investigation validated importance of mono- and di-substituted arylated triazine-based sulfanilamide derivatives in organic electronics. The structural identity of newly synthesized compounds was confirmed by 1H NMR, 13C NMR, and EI-MS analyses.

Does board activeness strengthen the relationship between structure of corporate ownership and firm performance?

This study empirically investigates the moderating effect of board activeness on the relationship between the structure of corporate ownership and firm performance. The objective was evaluated using the hierarchal panel regressions with data from non-financial companies of the Pakistan Stock Exchange from 2009 to 2018, operationalizing the ownership structure as state ownership, associated companies, foreign ownership, ownership concentration, institutional ownership, and family ownership, and firm performance as operating performance, financial performance, and stock market performance. The findings of the study revealed that operating, financial, and stock market performance were favorably influenced by the ownership stakes of the state, associated concerns, institutions, and foreigners. Family interests proved to be diverse for the firm performance. The isolated effect of the board consistently uplifted the firm productivity, but its interactional impact with all the ownership stakeholders postulated differential outcomes for internal and external performance. The study provides valuable insights for policymakers and investors to make optimal strategies to manage ownership interests and enhance value.

Nitric oxide regulates water status and associated enzymatic pathways to inhibit nutrients imbalance in maize (Zea mays L.) under drought stress.

Nitric oxide (NO) is a key signaling molecule that instigates significant changes in plant metabolic processes and promotes tolerance against various environmental stresses including drought. In this study, we focused on NO-mediated physiological mechanisms and enzymatic activities that influence the nutrient concentrations and yield in maize under drought stress. The drought-tolerant (NK-8711) and sensitive (P-1574) maize hybrids were sown in lysimeter tanks and two levels of water stress (well-watered at100% field capacity and drought stress at 60% field capacity) were applied at three-leaves stage of maize. Foliar treatment of sodium nitroprusside (SNP), the donor of NO was applied at the cob development stage. The results showed that the foliar spray of NO regulated water relations by increasing proline content and improved drought tolerance in water stressed maize plants. In addition, it stimulated the activity of antioxidative enzymes which reduced the production of free radicals and lipid peroxidation. The activities of nitrate assimilation enzymes were considerably increased by NO spray which, in turn, increased nutrient accumulation and yield in maize under water deficit conditions. These results acknowledge the importance of NO as a stress-signaling molecule that positively regulates defense mechanisms in maize to withstand water-limited conditions.