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We further demonstrated that itaconate attenuates reductive carboxylation at IDH2, restricting its own production and the accumulation of the immunomodulatory metabolites citrate and 2-hydroxyglutarate. In line with this, reductive carboxylation is enhanced in ACOD1-depleted macrophages. Mechanistically, the inhibition of IDH2 by itaconate is linked to the alteration of the mitochondrial NADP+/NADPH ratio and competitive succinate dehydrogenase inhibition. Taken together, our findings extend the current model of TCA cycle reprogramming during pro-inflammatory macrophage activation and identified novel regulatory properties of itaconate.5-HT2A receptors (5-HT2ARs) are widely expressed in the central nervous system, including in the ventrolateral orbital cortex (VLO). The VLO is an important cortical component for pain processing. Brain 5-HT2ARs are implicated in both pro- and anti- nociceptive functions. However, the roles of 5-HT2ARs in the VLO in trigeminal neuralgia and neuronal synaptic function remain to be understood. We used chronic constriction injury of infraorbital nerve (IoN-CCI) model and shRNA mediated gene knockdown in mice to investigate the role of 5-HT2ARs in the VLO in trigeminal neuralgia. We found that knockdown of 5-HT2ARs in the VLO aggravated spontaneous pain and mechanical allodynia in mice after IoN-CCI. At the synaptic level, decreasing 5-HT2AR expression by shRNA or inhibition of 5-HT2AR activity by its antagonist ketanserin decreased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of the neurons in the VLO, whereas 5-HT2AR partial agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) enhanced sEPSCs of the neurons in the VLO. In summary, 5-HT2ARs in the VLO modulate the trigeminal pain by regulating neuronal glutamatergic activity.The potent anti-cancer activity of naturally occurring organopolysulfides has attracted wide research attention over the last two decades. Sustained donation of hydrogen sulfide (H2S) from organopolysulfides is found to be beneficial for the treatment of several organ-specific cancers. In the present study, for the first time, the mechanism of action for the potent anti-cancer activity of bis(3,5-dimethoxybenzyl) trisulfide 4 against highly aggressive triple-negative breast cancer cells (MDA-MB-231) is described. Preliminary in vitro studies revealed potent anti-proliferative activity of the trisulfide 4 against triple-negative breast cancer cells with an IC50 value of 1.0 μM. Mechanistic studies reveal that the compound exhibited anti-cancer activity, primarily by targeting and suppressing the Wnt/β-catenin signaling pathway. The inactivation of the β-catenin level was associated with the cell cycle arrest in the G2/M phase and the significant down-regulation of downstream signaling genes such as Cyclin D1 and c-Myc expression. Several control experiments with analogous organosulfur compounds and the key enzyme inhibitors reveal that the presence of a trisulfide unit in the compound is crucial for the desired inactivation of β-catenin expression, which is promoted by GSK-3β-induced phosphorylation of β-catenin and its proteasomal degradation. Moreover, the trisulfide unit or the released H2S induced down-regulation of the p53 expression with the possible S-sulfhydration process led to p53-independent up-regulation of p21 expression. Therefore, the key results of this study highlighting the potency of synthetic benzylic organotrisulfide and the released H2S towards the growth inhibition of triple-negative breast cancer via Wnt/β-catenin signaling pathway would certainly be helpful for further studies and developing small-molecule anti-cancer therapeutics in future.Maternal hypothyroidism is associated with pre-eclampsia and intrauterine growth restriction, gestational diseases involving oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the placenta. However, it is not known whether hypothyroidism also causes OS and ERS at the maternal-fetal interface. The aim was to evaluate the fetal-placental development and the expression of mediators of OS and of the unfolded protein response (UPR) in the maternal-fetal interface of hypothyroid rats. Hypothyroidism was induced in Wistar rats with propylthiouracil and the fetal-placental development and placental and decidual expression of antioxidant, hypoxia, and UPR mediators were analyzed at 14 and 18 days of gestation (DG), as well the expression of 8-OHdG and MDA, and reactive oxygen species (ROS) and peroxynitrite levels. Hypothyroidism reduced fetal weight at 14 and 18 DG, in addition to increasing the percentage of fetal death and reducing the weight of the uteroplacental unit at 18 DG. At 14 DG, there was greater decidual and/or placental immunostaining of Hif1α, 8-OHdG, MDA, SOD1, GPx1/2, Grp78 and CHOP in hypothyroid rats, while there was a reduction in placental and/or decidual gene expression of Sod1, Gpx1, Atf6, Perk, Ho1, Xbp1, Grp78 and Chop in the same gestational period. At 18 DG, hypothyroidism increased the placental ROS levels and the decidual and/or placental immunostaining of HIF1α, 8-OHdG, MDA, ATF4, GRP78 and CHOP, while it reduced the immunostaining and enzymatic activity of SOD1, CAT, GST. Hypothyroidism increased the placental mRNA expression of Hifα, Nrf2, Sod2, Gpx1, Cat, Perk, Atf6 and Chop at 18 DG, while decreasing the decidual expression of Sod2, Cat and Atf6. These findings demonstrated that fetal-placental restriction in female rats with hypothyroidism is associated with hypoxia and dysregulation in placental and decidual expression of UPR mediators and antioxidant enzymes, and activation of oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface.

The purpose of this study was to examine the relationship of the serum creatinine/cystatin C ratio (CCR) with hand grip strength (HGS), total body muscle mass, trunk muscle mass, and skeletal muscle mass index (SMI) in patients attending a memory clinic.

This cross-sectional study enrolled outpatients of a memory clinic in Japan from October 2010 to July 2017.

We enrolled 1945 participants aged 60years or older with measured skeletal muscle mass, HGS, and serum creatinine and serum cystatin C levels.

Linear multiple regression analysis was performed for men and women using total body muscle mass, trunk muscle mass, and SMI as objective variables. The exposure variables were selected from previous reports if they were strongly linked to muscle mass. Total body muscle mass and trunk muscle mass were corrected by dividing by body weight. Multiple regression analysis was also conducted for men and women using HGS as an objective variable. Because cognitive function and HGS are strongly related, we also conducted sensitivity analysis by excluding participants with a Mini-Mental State Examination score<24 to alleviate any concern that we did not fully adjust for the effect of cognitive dysfunction.

In men, CCR was significantly associated with total body muscle mass, trunk muscle mass, and SMI (P=0.013, P=0.008, and P<0.001, respectively). In women, CCR was significantly associated with total body muscle mass and trunk muscle mass (P=0.013 and P<0.001, respectively), but not with SMI (P=0.932). On the other hand, CCR was significantly associated with grip strength in both men and women (P<0.001 and P<0.001, respectively).

CCR was associated with both muscle mass and muscle strength. This study suggests that CCR is a useful marker not only for muscle mass but also for muscle strength.

CCR was associated with both muscle mass and muscle strength. This study suggests that CCR is a useful marker not only for muscle mass but also for muscle strength.

The research aims to evaluate effects of the Tai Chi exercise therapy on glucose and lipid metabolism in patients with type 2 diabetes mellitus (T2DM).

Systematic review and meta-analysis of existing literature were undertaken.

Seven electronic resource databases were scanned to collect eligible studies. Two reviewers selected studies, the meta-analysis was performed with RevMan 5.3 after quality evaluation.

Nineteen RCT trails involved in 18 reports were included in the meta-analysis, involving 1220 research objects. The results show that the Tai Chi exercise group is better than the control group in decreasing fasting blood glucose (FBG) (MD=-0.79, 95%CI (-1.73, -0.68), p<0.0001), glycated hemoglobin (HbA1c) (MD=-1.10, 95% CI (-1.78, -0.43), p=0.001), triglyceride (TG) (MD=-0.23, 95% CI (-0.32, -0.15), p<0.0001) and in increasing the concentration of high-density lipoprotein cholesterol (HDL-C) (MD=0.15, 95% CI (0.11, 0.20), p<0.0001) of T2DM patients.

Tai Chi exercise therapy shows significant superiority in improving the FBG, HbA1c, TG, and HDL-C in T2DM patients. It can be used as one of the exercise prescriptions for prevention and treatment of T2DM patients.

Tai Chi exercise therapy shows significant superiority in improving the FBG, HbA1c, TG, and HDL-C in T2DM patients. It can be used as one of the exercise prescriptions for prevention and treatment of T2DM patients.

Tart cherries are rich in bioactive compounds, such as anthocyanins and other phytochemicals known to have antioxidant properties and exert cardiovascular protective effects. However, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of tart cherry juice consumption on cardio-metabolic risk factors.

A systematic search was conducted on electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar from inception up to December 2021 to identify eligible RCT studies. A random-effect model was utilized to estimate the weighted mean difference (WMD) and 95% confidence (95% CI).

Ten RCTs were included in the present meta-analysis. The pooled analysis revealed that tart cherry juice consumption led to a significant reduction in the fasting blood sugar (FBS) levels (WMD = -0.51mg/dl [95% CI -0.98, -0.06]). This lowering effect of FBS was robust in subgroups with cross-over studies, participants with age range ≥40, duration of follow-up ≤4 weeks, and baseline BMI ≥30. In contrast, tart cherry juice had no effect on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulin, body mass index (BMI), fat mass, systolic and diastolic blood pressure. However, in the subgroup analysis, some significant effects were observed for insulin, TG, TC, LDL-C, and HDL-C.

In summary, this meta-analysis showed that tart cherry juice mostly had a favorable effect on FBG levels. However, further RCTs with long-term intervention with different doses of administration are needed.

In summary, this meta-analysis showed that tart cherry juice mostly had a favorable effect on FBG levels. However, further RCTs with long-term intervention with different doses of administration are needed.We investigated whether vermal cerebellar low-frequency repetitive transcranial magnetic stimulation (crTMS) affects motor learning of visually guided postural tracking training (VTT) using foot center of pressure (COP) as well as the stability and sensory contribution of upright standing. Twenty-one healthy volunteers participated (10 in the sham-crTMS group and 11 in the active-crTMS group). For VTT, participants stood on the force plate 1.5 m from the monitor on which the COP and target moved in a circle. GGTI 298 purchase Participants tracked the target with their own COP for 1 min, and 10 VTT sessions were conducted. The tracking error (TE) was compared between trials. Active- or sham-crTMS sessions were conducted prior to VTT. At baseline (before crTMS), pre-VTT (after crTMS), and post-VTT, the COP trajectory during upright static standing under four conditions (eyes, open/closed; surface, hard/rubber) was recorded. Comparison of the length of the COP trajectory or path and sensory-contribution-rate showed no significant difference between baseline and pre- and post-VTT.