Oxidative stress and inflammatory condition has been broadly accepted being associated with the progression of diabetes. On the other hand, garlic (大蒜 dà suàn, bulb of Allium sativum) has been shown to possess both antioxidant and anti-inflammatory action in several clinical conditions. Our previous study demonstrated that treatment with garlic oil improves oral glucose tolerance and insulin tolerance and improves the insulin-stimulated utilization of glucose to synthesize glycogen in skeletal muscle in streptozotocin (STZ)-induced diabetes, in vivo and ex vivo, respectively. The aim of the present study is to investigate the antioxidant and anti-inflammatory effects of garlic oil (GO) in the skeletal muscle of diabetic rats. Rats with STZ-induced diabetes received GO (10, 50, or 100 mg/kg body weight) or corn oil by gavage every other day for 3 weeks. Control rats received corn oil only. GO dose-dependently improved insulin sensitivity, as assessed by the insulin tolerance test, and oral glucose tolerance. GO significantly elevated total glutathione and glutathione peroxidase activity and lowered the nitrate/nitrite content in skeletal muscle at 50 and 100 mg/kg and significantly elevated glutathione reductase activity and lowered lipid peroxidation at 100 mg/kg. By contrast, GO did not reverse diabetes-induced elevation of IL-1β and TNF-α in skeletal muscle at any tested dose. On the other hand, GO elevated the expression of GLUT4 in skeletal muscle along with glycogen content as observed with PAS staining. In conclusion, the antidiabetic effect of garlic oil is associated with ameliorated oxidative stress in skeletal muscle.

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ObjectiveWe aimed to investigate the efficacy and tolerability of cranial electrotherapy stimulation (CES) for patients with anxiety symptoms.MethodWe searched the Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Medline for randomized control trials (RCTs) from the time of inception until November 15, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random-effects model. The primary outcomes were the mean change scores for anxiety symptoms. The secondary outcomes were the mean change scores for depressive symptoms.ResultsEleven RCTs were eligible (n = 794, mean age: 41.4, mean population of female: 64.8%). CES significantly reduced the anxiety symptoms compared to the control group [k = 11, n = 692, Hedge's g = −0.625, 95% confidence intervals (CIs) = −0.952 to −0.298, P < 0.001] with moderate effect size. The subgroup analysis showed that CES reduced both primary and secondary anxiety (primary anxiety, k =3, n = 288, Hedges' g = −1.218, 95% CIs = −1.418 to −0.968, P = 0.007; secondary anxiety, k = 8, n = 504, Hedges' g = −0.334, 95% CIs = −0.570 to −0.098, P = 0.006). After performing between group analysis, we found CES has significant better efficacy for patients with primary anxiety than those with secondary anxiety (P < 0.001). For secondary outcome, CES significantly reduced depressive symptoms in patients with anxiety disorders (k = 8, n = 552, Hedges' g = −0.648, 95% CIs = −1.062 to −0.234, P = 0.002). No severe side effects were reported and the most commonly reported adverse events were ear discomfort and ear pain.ConclusionWe found CES is effective in reducing anxiety symptoms with moderate effect size in patients with both primary and secondary anxiety. Furthermore, CES was well-tolerated and acceptable.Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021267916.

Background: Although particular matter (PM) increases incidence and severity of idiopathic pulmonary fibrosis, the underlying mechanism remains elusive. Methods: The effects of PM were evaluated in a murine model of bleomycin-induced pulmonary fibrosis. Mice were divided into four groups, receiving: (1) Saline (control), (2) bleomycin, (3) PM, or (4) bleomycin plus PM (Bleo+PM). Additional groups of Bleo+PM mice were treated with sivelestat (an inhibitor of neutrophil elastase) or reparixin (a C-X-C motif chemokine receptor 2 antagonist), or were genetically modified with keratinocyte chemoattractant (KC) deletion. Results: Pulmonary fibrosis was not observed in the control or PM groups. Bleomycin induced pulmonary fibrosis within 14 days. The Bleo+PM group showed worse pulmonary fibrosis when compared to the bleomycin group. Analyses of immune cell profile and chemokine/cytokine concentrations at day 2-bronchoalveolar lavage fluid (BALF) revealed that the Bleo+PM group had increased neutrophil number and elastase level and KC concentration compared to the bleomycin group. Neutrophil elastase activated the Smad2/Smad3/α-SMA pathway to induce collagen deposition, while sivelestat abrogated the increased severity of pulmonary fibrosis caused by PM. Chemotaxis assay revealed that BALF of the Bleo+PM group recruited neutrophil, which was dependent on KC. Further, genetic KC deletion or pharmaceutical inhibition of KC binding to CXCR2 with reparixin ameliorated the PM-induced increased severity of pulmonary fibrosis. Conclusions: These data provide evidence that the PM-induced increased severity of pulmonary fibrosis depends on KC-mediated neutrophil chemotaxis and give additional mechanic insight that will aid in the development of therapeutic strategies.

Cancer stem cells (CSCs), a subpopulation of cancer cells responsible for tumor initiation and treatment failure, are more susceptible to ferroptosis-inducing agents than bulk cancer cells. However, regulatory pathways controlling ferroptosis, which can selectively induce CSC death, are not fully understood. Here, we demonstrate that the CSCs of esophageal squamous carcinoma cells enriched by spheroid culture have increased intracellular iron levels and lipid peroxidation, thereby increasing exposure to several products of lipid peroxidation, such as MDA and 4-HNE. However, CSCs do not reduce cell viability until glutathione is depleted by erastin treatment. Mechanistic studies revealed that damage from elevated lipid peroxidation is avoided through the activation of Hsp27, which upregulates GPX4 and thereby rescues CSCs from ferroptosis-induced cell death. Our results also revealed a correlation between phospho-Hsp27 and GPX4 expression levels and poor prognosis in patients with esophageal cancer. Together, these data indicate that targeting Hsp27 or GPX4 to block this intrinsic protective mechanism against ferroptosis is a potential treatment strategy for eradicating CSC in esophageal squamous cell carcinoma.