Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway.

Neurogenesis as a potential strategy to improve the consequences of intracerebral hemorrhage (ICH). The current study investigates the effects of withaferin A (WFA) in combination with leptin (LEP) on ICH and neurogenesis mechanisms. LEP levels were dramatically reduced on days 7 and 14 following ICH insults in mice, but continuous WFA therapy significantly improved the potency of intrinsic LEP on day 14 after ICH. Furthermore, WFA combined with LEP enhances intrinsic neurogenesis and lessen motor deficits and long-term cognitive outcomes after ICH. In parallel, leptin deficiency in ob/ob mice limits enhancement of neurogenesis following ICH in response to WFA combined with LEP treatment. Importantly, the functional recovery conferred by WFA combined with LEP after ICH was inhibited by neurogenesis suppression. Mechanistically, this study unveiled that the signal transducer and activator of transcription-3 (STAT3) / suppressor of cytokine signaling-3 (SOCS3) pathway is a critical signaling pathway through which WFA combined with LEP treatment promotes intrinsic neurogenesis after ICH. Collectively, the results of this study elucidate the neuroprotective effects of WFA and LEP in ICH, and highlight a potential approach for ICH cell therapy.

Genetic dissection of cold tolerance at the budding stage of rice in an indica-japonica recombination inbred line population.

Rice is highly cold-sensitive, and thus, the promotion of cold resistance in buds is essential. In this study, we conducted a mapping analysis to identify quantitative trait loci (QTLs) associated with cold tolerance in buds. The analysis was performed using a recombinant inbred line (RIL) population consisting of 192 lines derived from the cold-tolerant strain 02428 and the cold-sensitive strain YZX. Seven additive loci on chromosomes 1, 4, 5, and 6 were identified, of which loci 3 and 7 were found in two crop seasons, indicating stability. Three epistatic interactions, one present over two seasons, were found. Loci 3 and 7 pyramided with two main-effect QTLs observed to control the rate of low-temperature germination in our previous study. Two materials with good cold resistance at the germination and bud stages were obtained, namely, G93 and G146. Transcriptome sequencing analysis of the two parent buds after cold treatment found that genes expressed differentially between the two parents were related to photosynthesis, energy metabolism, and reactive oxygen scavenging. Five candidate genes, namely, Os01g0385400, Os01g0388000, Os06g0287700, Os06g0289200, and Os06g0291100, were selected in the two stable intervals based on gene expression profiles and annotations. These genetic loci exhibit strong potential as targets for breeding cold tolerance in buds and require additional investigation. In conclusion, this work provides valuable genetic resources that can be utilized to improve the cold tolerance of rice.

Acoustic source localization using L-shaped sensor clusters: A review.

Acoustic source localization (ASL) plays an important role in structural health monitoring (SHM). The L-shaped sensor cluster (LSSC) is very convenient for ASL, and hence SHM. Various techniques based on LSSC have been developed rapidly in the past decade. LSSC can be conveniently used for damage detection and localization, a necessary step for monitoring structures through non-destructive testing (NDT). After ten years of development, LSSC still has a wide development space. In this paper, the fundamental roles of LSSC in developing different techniques within last ten years and its future potentials are discussed. The LSSC-based time difference of arrival localization techniques and the wave front shape-based localization techniques are reviewed in detail in this paper. This paper aims to give readers a more comprehensive and clear understanding of these techniques. The discussion on the advantages and disadvantages of these techniques and various sources of the errors will give the readers the current limitations and future development prospects of ASL and damage detection techniques using LSSC.

Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage.

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage (ICH). Withaferin A (WFA), a natural compound, exhibits a positive effect on a number of neurological diseases. However, the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown. In this study, we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis. We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH. WFA was injected intracerebroventricularly at 0.1, 1 or 5 µg/kg once daily for 7 days, starting immediately after ICH operation. WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage. Through in vitro experiments, cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury. Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde, an oxidative stress marker, and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH. Western blot assay, quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis, promoted translocation of Nrf2 from the cytoplasm to nucleus, and increased HO-1 expression. Silencing Nrf2 with siRNA completely reversed HO-1 expression, oxidative stress and protective effects of WFA. Furthermore, WFA reduced hemin-induced ferroptosis. However, after treatment with an HO-1 inhibitor, the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened. MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury. Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway, which may highlight a potential role of WFA for the treatment of ICH.

[Effect of electroacupuncture on visceral sensitivity and colonic NGF, TrkA, TRPV1 expression in IBS-D rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg-1•d-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION: Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.

Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage.

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.

[Effect of electroacupuncture on colonic motility and RhoA and ROCK protein expression in IBS-D rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Tianshu"(ST25) and "Shangjuxu"(ST37)on gastrointestinal motility, psychological abnormality and expression of RhoA and ROCK protein in rats with diarrhea predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in improving IBS-D. METHODS: Thirty-six male rats were randomly and equally divided into control, model, EA and medication groups (n=9 in each group). The IBS-D model with psychological abnormality was established by gavage of dinitrobenzene sulfonic acid (DNBS) + chronic restraint stress. EA (2 Hz/100 Hz, 0.3 mA) was applied to bilateral ST25 and ST37 for 20 min, once a day for 7 days. Rats of the medication group received gavage of pinaverium bromide solution (15 mg/kg), once a day for 7 days. The rats' food intake in 24 h, body mass and colonic contraction waves were recorded. The anhedonia-related behavior was measured using the sucrose consumption test. The elevated plus maze test (the open-arm residence time ratio) was used to assess the anxiety-like behavior. The small intestinal propulsion rate test was used to assess the intestinal motility. The expression levels of RhoA and ROCK proteins in the colonic tissue were measured by Western blot. RESULTS: After modeling, the body mass, food consumption, sucrose preference index, the open-arm residence time ratio andlatency of colonic contraction waves were significantly decreased (P<0.05), and the number of contraction waves, intestinal propulsive rate, and the expression levels of RhoA and ROCK proteins considerably increased (P<0.01，P<0.05) in the model group relevant to the control group. Following the interventions, the decrease of body mass, food consumption, sucrose preference index, open-arm residence time ratio and latency of contraction waves, and the increase of the contraction waves, intestinal propulsive rate, and the expression levels of RhoA and ROCK proteins were all reversed by both EA and medication (P<0.05，P<0.01). The effect of EA was significantly superior to that of medication in increasing the sucrose pre-ference index (P<0.05). CONCLUSION: EA can improve both colonic motility and psychological disorders in IBS-D rats with psychological disorder, which may be related to its function in down-regulating the expression of colonic RhoA and ROCK proteins.

Hemorrhage-Induced Sphingosine Kinase 1 Contributes to Ferroptosis-Mediated Secondary Brain Injury in Intracerebral Hemorrhage.

The pathogenic processes of brain injury after intracerebral hemorrhage (ICH) have not yet been fully elucidated. Increasing evidence suggests that ferroptosis activation aggravates injury after ICH, but the underlying mechanism remains unclear. Sphingosine kinase 1 (Sphk1) is a key enzyme in the regulation of sphingosine metabolism involved in the ferroptosis pathway, but its role in ICH needs clarification. In this study, transcriptional changes in ICH patients were assessed by microarray data, exposing Sphk1 as a highly upregulated gene during ICH. Furthermore, Sphk1 chemical inhibitors and siRNA were used to inhibit ICH-induced Sphk1 upregulation in in vivo and in vitro models, showing that Sphk1 inhibition after protects against ferroptosis and attenuates secondary brain injury and cell death. Mechanistically, this study unveiled that sphingosine kinase 1/sphingosine 1-phosphate/extracellular-regulated protein kinases/phosphorylated extracellular-regulated protein kinases (Sphk1/S1p/ERK/p-ERK) pathway is responsible for regulation of ferroptosis leading to secondary brain injury and cell death following ICH. Collectively, this study demonstrates that ferroptosis is closely associated with ICH, and that Sphk1 has a critical role in this lethal process. These results suggest a novel unique and effective therapeutic approach for ICH prevention and treatment.

[Acupuncture and moxibustion treatment for dry eye disease: a network Meta-analysis of rando-mized controlled trial].

OBJECTIVE: A network Meta-analysis based on Bayesian theory was used to evaluate efficacy and safety of acupuncture and moxibustion in the treatment of dry eye disease(DED), so as to provide evidence-based research basis for clinical application. METHODS: Randomized controlled trials (RCT) for acupuncture and moxibustion treatment of DED published from the inception of database to November 25, 2020 were searched from PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang and VIP Database. Two reviewers independently screened the literatures, extracted the data. The quality of the included literature was evaluated, and network Meta-analysis was performed by using Stata14.0 and R4.0.3 software. RESULTS: A total of 71 literatures were identified, including 5 536 patients with DED, covering 11 different interventions. Network Meta-analysis showed that acupuncture+traditional Chinese medicine+artificial tears was the best treatment option in terms of the clinical effective rate, breakup time of tear film (BUT), Schirmer I test (SIT) with surface under cumulative ranking area value. Acupuncture+traditional Chinese medicine+artificial tears was better than artificial tears in the clinical effective rate (odds ratio［OR］=12.34, 95% confidence interval［CI］［4.72, 36.89］), BUT(mean differenc［MD］=2.76, 95%CI［0.16, 5.40］), SIT(MD=4.76, 95%CI［1.23, 8.29］). CONCLUSION: Acupuncture and moxibustion in the treatment of DED are generally better than artificial tears, and acupuncture-moxibustion combined with other traditional Chinese medicine therapy has the best effect.

OIP5-AS1: A Fascinating Long Noncoding RNA in Carcinoma.

BACKGROUND: It is substantiated that LncRNAs are associated with carcinoma progression. OIP5- AS1 is a tumor-related carcinoma suppressor lncRNA, previously discovered in zebrafish, which is involved in the progression of a variety of cancers, has a regulatory effect on carcinoma, and interacts with miRNA and other biomolecules to affect the physiological and pathological processes of carcinoma cells. This article will discuss the effect of OIP5-AS1 in various cancers and its regulatory mechanism. METHODS: This paper summarized and analyzed OIP5-AS1, which functions on the germination and progression of carcinoma and its regulatory mechanism. Meanwhile, the related research was retrieved and collected by the PubMed system. RESULT: OIP5-AS1 is overexpressed in various tumors, which regulates and controls tumor growth and participates in tumor progression, including breast carcinoma, ovarian carcinoma, cervical carcinoma, lung carcinoma, laryngeal squamous cell gastric carcinoma and hepatocellular carcinoma. The research evidence proves that OIP5-AS1 takes part in carcinoma proliferation, growth, migration, invasion, and apoptosis. CONCLUSION: OIP5-AS1 probably can be an effective biomarker or a potential therapeutic target in multiple tumors.

Critical Functions of lncRNA DGCR5 in Cancers of the Digestive System.

BACKGROUND: Long non-coding RNAs (lncRNAs) has no protein-coding potential due to the lack of an apparent open reading frame. There is growing evidence that lncRNA DGCR5 has a vital regulatory role in human illnesses' pathological development, particularly in the digestive system's carcinogenesis and progression. Abnormal DGCR5 expression affects different cellular functions such as proliferation, aggression, and metastasis. This paper aims to probe into the pathophysiological functions and molecular mechanisms of DGCR5 in cancers of the digestive system. METHODS: This review summarizes and analyzes the biological functions and mechanisms of lncRNA DGCR5 in digestive system cancers occurrence. Relevant studies were conducted and reviewed by searching PubMed for articles with lncRNA DGCR5 and digestive system cancer as keywords in recent years. RESULTS: DCGR5, as a novel tumor-related lncRNA, is recently identified to be abnormally expressed in digestive system cancers, such as pancreatic ductal adenocarcinoma, pancreatic cancer, gastric cancer, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma. The role played by DCGR5 is vital and varies in different digestive cancers. Taken together, aberrant expression of DCGR5 regulates the progression of digestive cancers by affecting cancer cell proliferation, aggression, metastasis, and drug resistance. CONCLUSION: LncRNA DGCR5 might be a viable marker or a promising therapeutic target in digestive system cancers.

[Effect of acupuncture on intestinal flora and TLR4 in brain and intestinal tissues in rats with stress gastric ulcer].

OBJECTIVE: To observe the effect of acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) on intestinal flora and Toll-like receptors-4 (TLR4) in brain and intestinal tissue in rats with stress gastric ulcer (SGU), and to explore the possible mechanism of acupuncture for SGU. METHODS: Thirty-one male SD rats were randomly divided into a blank group (n=7), a model group (n=8), an acupuncture group (n=8) and a drug group (n=8). The rats in the model group, acupuncture group and drug group were treated with modified restraint plus water-immersion stress method to establish SGU model. After modeling, the rats in the acupuncture group were treated with acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39), 20 min each time, and the needles were twirled for 30 s every 5 min. The rats in the drug group were treated with intragastric administration of 2 mL omeprazole enteric-coated tablets (20 mg/mL). Both the treatments were given once a day for 5 days. After the intervention, the gastric mucosal damage index was calculated by Guth method; the morphological changes of gastric mucosa were observed by HE staining; the diversity of intestinal flora was detected by 16S rDNA high-throughput sequencing; TLR4 contents in brain and intestinal tissues were determined by ELISA. RESULTS: Compared with the blank group, the gastric mucosal damage index was significantly increased in the model group (P<0.01); the morphological changes of gastric mucosa were obvious; the Observed Species index and Shannon index of α diversity index of intestinal flora were decreased (P<0.05); the ß diversity showed that the spatial distance between the model group and the blank group was far; the TLR4 contents in the brain and intestinal tissue were increased (P<0.05, P<0.01). Compared with the model group, the gastric mucosal damage index was decreased in the acupuncture group and the drug group (P<0.05); the morphology of gastric mucosa was improved; the Observed Species index and Shannon index of α diversity index of intestinal flora in the acupuncture group was increased (P<0.05), and the Shannon index in the drug group was increased (P<0.05); the ß diversity showed that the spatial distance between the acupuncture group and the blank group was close; the TLR4 contents in the brain and intestinal tissues of the acupuncture group were decreased (P<0.01). Compared with the drug group, the contents of TLR4 in the intestinal tissue of the acupuncture group were decreased (P<0.05). CONCLUSION: Acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) could alleviate SGU in rats, and its mechanism may be related to increasing the diversity of intestinal flora, promoting the disorder of intestinal flora to normal, and reducing the overexpression of TLR4 in brain and intestinal tissues.

The Function of LncRNA FTX in Several Common Cancers.

BACKGROUND: LncRNA is a kind of non-coding RNA and its research is more popular in recent years, which has more than 200 nucleotides. It plays a significant part in various biological functions, including chromosome modification, genome modification, transcriptional activation, transcriptional interference, and other processes. FTX, at the center of the X chromosome inactivation and it has been shown that lncRNA FTX regulates cancer cells' development, migration, and invasion in many studies. METHODS: Relevant literature was collected through the PubMed system search and is summarized in this article. RESULTS: LncRNA FTX abnormally increased in tumor cells, such as liver cancer, stomach cancer, leukemia, renal cell carcinoma, colorectal cancer, glioma, osteosarcoma, etc. However, the expression level decreased in temporal lobe epilepsy, liver cirrhosis, heart failure, etc. Conclusion: FTX may be an important regulatory factor and a potential therapeutic target in cancers.

[Effect of acupuncture on intestinal flora in rats with stress gastric ulcer].

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery. METHODS: Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora. RESULTS: Compared with the control group, the GMDI of rats in the model group was increased (P<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (P<0.05), the diversity index Simpson was increased (P<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (P<0.01, P<0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (P<0.05) and the diversity index Simpson decreased (P<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (P<0.01), the recovery of gastric mucosal injury was better than that of the medication group. CONCLUSION: Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.

[Effect of acupuncture on serum inflammatory cytokines and intestinal flora in rats with stress-induced gastric ulcer].

OBJECTIVE: To investigate the effect of acupuncture on serum inflammatory cytokines and intestinal flora in rats with stress-induced gastric ulcer (SGU), and to explore the mechanism of acupuncture in the treatment of SGU. METHODS: Sprague-Dawley rats were randomly divided into blank, model, acupuncture, and medication groups, with 7 rats in each group. Restraint water-immersion stress was used to establish the model of SGU. The rats in the acupuncture group were given acupuncture at "Zhongwan"(CV12) and bilateral "Zusanli"(ST36) for 20 min, once a day for 5 days, and those in the medication group were given 2 mL solution of Omeprazole enteric-coated tablets (0.2 mg/kg) by gavage, once a day for 5 days. The Guth method was used to calculate the gastric mucosa damage index, HE staining was used to observe the histopathological changes of the gastric mucosa, ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), and 16S rDNA sequencing method was used to observe the change in intestinal flora. RESULTS: Compared with the blank group, the model group had a significant increase in gastric mucosa damage index (P<0.01), markedly pathological changes of the gastric mucosa shown by HE staining, a significant reduction in the content of serum IL-4 (P<0.01), and a significant increase in the content of serum IL-6 (P<0.01), as well as a significant reduction in Bacteroidetes and Firmicutes at the phylum level. Compared with the model group, the acupuncture group and the medication group had a significant reduction in gastric mucosa damage index (P<0.01, P<0.05). HE staining showed reduced pathological changes of the gastric mucosa, as well as a significant increase in the content of serum IL-4 (P<0.01, P<0.05) and a significant reduction in the content of serum IL-6 (P<0.01, P<0.05). As for the intestinal flora, there was a significant increase in Bacteroidetes. Compared with the medication group, the gastric mucosa damage index was decreased （P<0.05），the content of serum IL-4 was significantly increased （P<0.05）, while the content of serum IL-6 significantly decreased (P<0.05) in the acupuncture group. CONCLUSION: Acupuncture at CV12 and ST36 can down-regulate the content of serum IL-6, up-regulate the content of serum IL-4, maintain the relative homeostasis of inflammatory cytokines, and regulate the community structure of intestinal flora, and thus help to repair the damage of gastric mucosa.

Withaferin A alleviates traumatic brain injury induced secondary brain injury via suppressing apoptosis in endothelia cells and modulating activation in the microglia.

Traumatic brain injury (TBI) is a major public health concern with high rates of morbidity and mortality worldwide. Currently used medications, though effective, are also associated with several adverse effects. Development of effective neuroprotective agents with fewer side-effects would be of clinical value. Previous studies have shown that withaferin compounds have a potential neuroprotective effect in nervous system disorders. However, the effect of withaferin compounds, especially withaferin A (WFA), on traumatic brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether WFA could exert a neuroprotective effect after TBI and were used to explore the associated mechanisms. The results showed that WFA significantly improved neurobehavioral function in a dose-dependent fashion and alleviated histological alteration of injury to tissues in TBI mice. In vitro models of TBI revealed that dose-dependent WFA treatment increased the viability of SH-SY5Y cells. In addition, WFA treatment could attenuate blood-brain barrier disruption and brain edema via suppressing apoptosis in endothelial cells. Furthermore, both our in vivo and in vitro results reveal that WFA treatment could significantly reduce levels of several neuroinflammation cytokines (IL-1ß, IL-6, and TNF-α), which correlate with an overall reduction in microglial activation. These data suggest that the neuroprotection by WFA is, at least in part, related to regulation of microglial activation and inhibition of vascular endothelial cell apoptosis. Taken together, these findings support further investigation of WFA as a promising therapeutic agent for promoting functional recovery after traumatic brain injury.

Glutathione alleviates acute intracerebral hemorrhage injury via reversing mitochondrial dysfunction.

Glutathione (GSH) has been studied for its neuroprotection value in several diseases, but the effect of GSH on intracerebral hemorrhage (ICH) is unclear. In this study, we examined the protective effects of GSH in an experimentally induced ICH model and investigated the relative mechanisms. Adult male C57BL/6j mice were randomized into Sham, ICH and GSH treatment groups. GSH was injected with the dose of 50, 100 or 200 mg/kg once per day for 3 days, starting immediately after operation. The results revealed a GSH-mediated improvement of neurological deficits score (NDS), motor and sensory functions impairment in a dose-dependent manner three days post ICH (p < 0.01, GSH 200 vs ICH. Sham, n = 12; ICH, n = 9; GSH 50, n = 10; GSH 100, n = 10; GSH 200, n = 11) in addition to significantly reduced mortality rate (p = 0.2632, GSH 200 vs ICH. n = 12 per group) and damage volume (p < 0.05, GSH 200 vs ICH. n = 12 per group). GSH treatment also attenuated injury measured by decreased brain edema (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), blood-brain barrier disruption (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), and histopathological damage (p < 0.05, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) 72 h after ICH. In addition, GSH treatment also decreased cell apoptosis (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) and resulted in up-regulated protein expression of complex I (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8), which was consistent with an overall up-regulation of complex I function in mitochondria using Oxygraph-2 K high resolution respirometry (p < 0.05, GSH 200 vs ICH. Sham, n = 4; ICH, n = 5; GSH 200, n = 6). In conclusion, GSH effectively improved the prognosis of ICH mice by attenuating neurological impairment, decreasing neural damage, and inhibiting apoptosis. The neuroprotection by GSH resulted from the up-regulation of mitochondrial oxidative respiration function. The results of our study suggest that GSH can be a potential therapeutic agent for ICH.