Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders.

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as a promising candidate for the prevention and treatment of conditions affecting the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other neurological disorders. These effects also include neuroprotection in epilepsy models, as evidenced by a reduction in seizure-like behavior, cell death in specific hippocampal regions, and lowered neuroinflammatory markers. In AD, SA treatment enhances memory, reverses cognitive deficits, and attenuates astrocyte activation. SA also has positive effects on cognition by improving memory and lowering oxidative stress. This is shown by lower levels of oxidative stress markers, higher levels of antioxidant enzyme activity, and better memory retention. Additionally, in ischemic stroke and PD models, SA provides microglial protection and exerts anti-inflammatory effects. This review emphasizes SA's multifaceted neuroprotective properties and its potential role in the prevention and treatment of various brain disorders. Despite the need for further research to fully understand its mechanisms of action and clinical applicability, SA stands out as a valuable bioactive compound in the ongoing quest to combat neurodegenerative diseases and enhance the quality of life for affected individuals.

Comprehensive assessment of TECENTRIQ® and OPDIVO®: analyzing immunotherapy indications withdrawn in triple-negative breast cancer and hepatocellular carcinoma.

Atezolizumab (TECENTRIQ®) and nivolumab (OPDIVO®) are both immunotherapeutic indications targeting programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 (PD-1), respectively. These inhibitors hold promise as therapies for triple-negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) and have demonstrated encouraging results in reducing the progression and spread of tumors. However, due to their adverse effects and low response rates, the US Food and Drug Administration (FDA) has withdrawn the approval of atezolizumab in TNBC and nivolumab in HCC treatment. The withdrawals of atezolizumab and nivolumab have raised concerns regarding their effectiveness and the ability to predict treatment responses. Therefore, the current study aims to investigate the immunotherapy withdrawal of PD-1/PD-L1 inhibitors, specifically atezolizumab for TNBC and nivolumab for HCC. This study will examine both the structural and clinical aspects. This review provides detailed insights into the structure of the PD-1 receptor and its ligands, the interactions between PD-1 and PD-L1, and their interactions with the withdrawn antibodies (atezolizumab and nivolumab) as well as PD-1 and PD-L1 modifications. In addition, this review further assesses these antibodies in the context of TNBC and HCC. It seeks to elucidate the factors that contribute to diverse responses to PD-1/PD-L1 therapy in different types of cancer and propose approaches for predicting responses, mitigating the potential risks linked to therapy withdrawals, and optimizing patient outcomes. By better understanding the mechanisms underlying responses to PD-1/PD-L1 therapy and developing strategies to predict these responses, it is possible to create more efficient treatments for TNBC and HCC.

The effect of co-administration of artemisinin and N-acetyl cysteine on antioxidant status, spermatological parameters and histopathology of testis in adult male mice.

OBJECTIVES: This in vivo study aimed to evaluate the effect of various concentrations of artemisinin (Art) alone or together with N-acetyl cysteine (NAC) on spermatological indices, antioxidant status, and histopathological parameters of testicular tissue in adult male mice. METHODS: Six groups of five healthy male mice (25-30 g) were randomly assigned to different experimental groups. These groups received DMSO and corn oil (0.1%) as an Art solvent (Control), 50 mg kg-1 Art (Art-50), 250 mg kg-1 Art (Art-250), 50 mg kg-1 Art + 150 mg kg-1 NAC (Art-50+NAC-150), 250 mg kg-1 Art + 150 mg kg-1 NAC (Art-250+NAC-150) and 150 mg kg-1 NAC (NAC-150) for a period of 7 days. Testes and epididymis were prepared to evaluate the malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), spermatological indices, and histological parameters. RESULTS: We showed that the high dose of Art (Art-250) significantly reduced the sperm count, motility, viability, and the activity of CAT and increased the levels of MDA compared to the control group. Also, the overdose of Art caused adverse changes in testicular tissue. Co-administration of NAC with Art (Art-250+NAC-150) corrected the adverse effects of Art. CONCLUSIONS: The current study reports that a high dose of Art affects, spermatological parameters, antioxidant/stress oxidative status of the male reproductive system, and NAC is capable neutralize all adverse effects caused by Art.

Interaction of lithium and sleep deprivation on memory performance and anxiety-like behavior in male Wistar rats.

Sleep plays a crucial role in the modulation of physiological and cognitive functions. Many studies have reported the impairment effect of sleep deprivation (SD) on cognitive functions such as learning and memory. On the other hand, lithium as one of the oldest drugs used for the treatment of psychiatric disorders, affects cognitive functions and mood state. In this study, we aimed to assess the effect of lithium, SD (for 24 h), and the interaction effect of SD and lithium, on memory function and anxiety-like behavior. The water box, the shuttle box, elevated plus maze, and the three-chamber paradigm test were used to evaluate rat's behavior. Also, lithium was injected intraperitoneal at the doses of 10 and 20 mg/kg, for three consecutive days. The results showed that SD impaired passive avoidance memory and social interaction memory, and decreased anxiety-like behavior. Lithium also impaired passive avoidance memory and induced an anxiolytic effect, while it improved social interaction memory and reversed the impairment effect of SD on social interaction memory. In conclusion, we suggested that interaction effect of SD and lithium on the function of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase3-ß (GSK3-ß) may be involved in the modulation of cognitive functions. As a limitation of this research, it was declared that we did not evaluate the function of GSK3-ß and BDNF in the brain of rats, especially in the hippocampus. We suggested conducting more studies focusing on the interaction of SD and lithium on the function of BDNF and GSK3-ß, and on different cognitive functions.

The association between dietary intake of white rice and central obesity in obese adults.

BACKGROUND: Obesity has become one of the most important and the fastest growing health and nutritional problem, not only in developed but also in developing countries. White rice consumption causes an increase in postprandial blood glucose and could be a probable reason for obesity. This study was conducted to investigate the association between intake of white rice and central obesity in an Iranian population. METHODS: In the present cross-sectional study, a total of 212 subjects were selected based on convenience non-random sampling procedure. Expert interviewers collected socio-demographic and dietary intake data by a face to face method. RESULTS: We failed to find any significant association between frequency of white rice consumption and body mass index or waist circumference, neither in crude model nor in adjusted models. CONCLUSION: Although there was no significant association between white rice intake and obesity factors in our study, more studies are necessary with larger population and better design.