ABSTRACT
Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.
ABSTRACT
Background and objective: Antidepressants are widely prescribed to treat depression and anxiety disorders that may become chronic conditions among women. Epidemiological studies have yielded inconsistent results on the correlation between antidepressant use and the incidence risk of female breast and gynecological cancer, along with uncertain dose-response relationship. Therefore, we performed a systematic review and dose-response meta-analysis to investigate the association. Methods: Web of Science, Embase, PubMed, The Cochrane Library, and PsycINFO were systematically searched in January 2022, with no language limits. Random-effect models were used to calculate pooled effect sizes and 95% confidence intervals between studies. Linear and non-linear dose-response analyses were performed to evaluate the dose or duration of antidepressant use affecting the incidence risk of female breast and gynecological cancer. Further subgroup analyses were systematically performed by stratifying almost all study characteristics and important potential confounders, in order to further clarify and validate the important potential hypotheses regarding the biological mechanism underlying this association. Results: Based on a systematic literature search, 34 eligible studies (27 case-control studies and 7 cohort studies) involving 160,727 female breast and gynecological cancer patients found that antidepressant use did not increase the incidence risk of female breast and gynecological cancer (pooled OR: 1.01; 95% CI: 0.97, 1.04, I² = 71.5%, p < 0.001), and even decreased the incidence risk of ovarian cancer (pooled OR: 0.91; 95% CI: 0.83, 1, I² = 17.4%, p = 0.293). There were a non-linear dose-response relationship (p non-linearity < 0.05) between the duration of antidepressant use and incidence risk of female breast cancer, and an inverse linear dose-response relationship between antidepressant use and the incidence risk of gynecological cancer, specifically with an increase of cumulative defined daily dose or duration to a high level, like 25,550 doses (OR: 0.91, 95% CI: 0.85-0.98, p linearity < 0.05) or 4,380 days (OR: 0.82; 95% CI: 0.7, 0.96, p linearity < 0.05), compared to never antidepressant users. Conclusion: This systematic review and dose-response meta-analysis found that antidepressant use did not increase the incidence risk of female breast and gynecological cancer and even decreased the incidence risk of ovarian cancer, along with a non-linear or linear dose-response relationship. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=313364, identifier CRD42022313364.
ABSTRACT
[This corrects the article DOI: 10.3389/fonc.2022.939636.].
ABSTRACT
Ginger, a widely used functional food and food additive, little is known about the effect of ginger juice, which is rich in many healthful agents, on healthy humans or on its relationship with gut microbiota composition variation. The aim of this study was to investigate the changes in the gut microbial communities that occur following the supplementation of fresh ginger-derived juice in healthy adults and its potential associations with function. A crossover intervention study in which 123 healthy subjects (63 men and 60 women) consumed fresh ginger juice from Zingiber officinale Rosc. or sterile 0.9% sodium chloride was conducted. 16S rRNA sequencing analyses were applied to characterize gut microbiota variation. We found that ginger juice intervention increased the species number of intestinal flora. A decreased relative abundance of the Prevotella-to-Bacteroides ratio and pro-inflammatory Ruminococcus_1 and Ruminococcus_2 while a tendency toward an increased Firmicutes-to-Bacteroidetes ratio, Proteobacteria and anti-inflammatory Faecalibacterium were found. When we did not consider gender, we found differences in bacterial diversity both in community evenness and in richness caused by ginger intervention. In fact, there were different changes in bacterial α-diversity induced by the ginger juice in men and women. We identified 19 bacterial genera with significant differences between the control group (women) and ginger group (women) and 15 significant differences between the control group (men) and ginger group (men) at the genus level. Our results showed that short-term intake of ginger juice had substantial effects on the composition and function of gut microbiota in healthy people. Moreover, our findings underscored the importance of analyzing both male and female individuals to investigate the effects of ginger on gut microbiota. Additional studies are necessary to confirm these findings.
ABSTRACT
Berberine is a plant alkaloid that can be extracted from many Chinese herbs. It has been reported that berberine could protect mice from ulcerative colitis, but the mechanism remains unclear. The current study's aim was to determine the potential mechanism by which berberine exhibits its anti-inflammatory function. Mice with colitis induced by dextran sulfate sodium (DSS) were administered with berberine at 50 mg/kg by gavage. Berberine significantly increased the proportion of regulatory T cells (Treg cells). The targeted metabolomics analysis was then performed to find that glutamine and glutamate metabolism played an important role in the process of regulating immune response. mTORC1 pathway was reported to closely relate with glutamine metabolism. As a result, the relative expression levels of downstream effector genes of mTORC were further determined, and data obtained showed that berberine could significantly increase the relative expression levels of S6K1 and 4EBP1. In addition, rapamycin was used to inhibit mTORC1 signaling, and it was found that colon length, disease associated index (DAI), and proportion of Treg cells of mice in the rapamycin-DSS group were not different from those of mice in the rapamycin/berberine-DSS group. Together, these results suggest that berberine exhibits significant protective effects against DSS colitis by activating the mTORC1 pathway to increase the proportion of Treg cells.
