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Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-β. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-β in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future. [Image: see text]

Compound 511 (511) is specially developed for opioid addiction treatment based on the Ancient Chinese drug rehabilitation literature, and its composition has profound effects in the treatment of drug addiction in various clinical trials and animal experiments. The effect of 511 on the rewarding properties of morphine and craving responses and its potential mechanisms remain unclear. Here, we have applied a conditioned place preference (CPP) paradigm in mice to measure morphine-induced rewarding effects under the treatment of 511. Then we used the RNA sequencing strategy to screen its potential mechanisms. In our research, firstly, we found 511 could decrease CPP score, locomotor activity, self-administration, jumping behavior, weight loss, wet-dog shakes, and stereotyped behavior. Then the brain VTA region tissues were performed mRNA sequencing to detect potential mechanisms. We found the brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) were downregulated in morphine-induced CPP, whereas the decreased BDNF and TrkB were reversed after 511 treatment. We retested the levels of BDNF and TrkB using qRT-PCR and Western blot and found the similar results to mRNA sequencing. It has been widely reported that BDNF-TrkB signaling in the VTA is involved in multiple facets of addiction, including reward and motivation, so we focused on the BDNF-TrkB signaling to investigate the anti-addiction mechanisms of 511 in morphine addiction mice. We studied the downstream pathway of BDNF-TrkB and the soma size of dopaminergic neurons. The results showed 511 could increase the phosphorylation levels of PI3K and AKT, which were decreased in morphine-induced CPP. Simultaneously, 511 could decrease the level of PLCγ1 and the phosphorylation levels of ERK and S6K, which were increased in morphine-induced CPP. In addition, 511 also enlarged the soma size of VTA dopaminergic neurons, which was reduced in morphine-induced CPP. Hence, our research indicated 511 maybe mediate the BDNF-TrkB signaling in VTA to improve morphine addiction behavior.

Background. Simple obesity has become a global risk to health of human beings. Acupuncture, as one of traditional Chinese medicine therapies, has been widely used in obesity treatment in recent years. However, the individual heterogeneity which makes acupuncture’s efficiency unstable leads to some controversy. So more evidence-based results are necessary to judge the effectiveness of acupuncture in treatment of simple obesity. Compared with clinical trials, animal experiments are controllable, and the underlying mechanism is more likely to be explored. Last but not the least, more and more experimental studies on acupuncture for animal obesity have been published. Therefore, we conducted the systematic review and meta-analysis to evaluate the effectiveness of acupuncture in treating simple obesity in animal experiments. Methods. Randomized Controlled Trials (RCTs) on acupuncture for simple obesity animal models were searched from six databases: PubMed, MEDLINE, CNKI, VIP, WanFang Date, and CMB from inception to February 2017 and updated on April 12, 2019. RevMan 5.3 software was used for meta-analysis. Treatment effects were summarized as relative risk (RR) and Standard mean difference (SMD) with 95% of confidence interval (CI). Results. A total of 108 trials involving 5731 rats were included. Meta-analysis showed that acupuncture had better effect on reducing weight (SMD -2.60, 95%CI: -2.93 to -2.26, p Conclusions. Our review provided positive evidence of acupuncture for simple obesity. Unfortunately, none of the firm conclusions can be drawn due to methodological flaws, high heterogeneity, and publication bias. More high-quality trials are needed in future to get objective conclusions.

Myocardial infarction (MI), the most common symptom is chest pain, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. Electroacupuncture pretreatment (EP) is a recent observation which has been shown to induce ischemic tolerance like the ischemia preconditioning, suggesting that EP may be a promising preventive strategy for individual susceptibility to MI. This study investigated mechanisms that underlie the effect of EP on MI through the use of gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling. Male Sprague-Dawley rats were randomly divided to receive or not receive three days of EP at PC6 (Neiguan). Then on the fourth day, each group was further divided to undergo mock surgery or MI, induced by ligation of the left anterior descending coronary artery. After 24[Formula: see text]h, the blood samples and hearts were collected for the follow-up research. The results showed that treatment by EP significantly reduced the levels of CK-MB, cTnT, AST, and MDH in serum and decreased myocardial infarction area. According to GC-MS-based serum metabolic profiling and analysis, a total of 636 characteristic peaks were identified, including 158 known and 478 unknown metabolites. MI caused comprehensive metabolic changes in glycolysis-related metabolites, malate-aspartate shuttle (MAS) metabolites, and purine metabolites with anti-oxidant functions, while EP reversed more than half of the differential metabolic changes, mainly affecting amino acid and energy metabolism, especially the glutamate metabolism and MAS. In a word, our findings suggest that EP exerts its cardioprotective effect on MI by regulating amino acid and energy metabolisms. Meanwhile, GC-MS-based metabolomics provided a powerful way to characterize the metabolic features of MI, with and without EP, and thereby improved our understanding of the effect and mechanisms of EP.

BackgroundPrevious studies had suggested that electroacupuncture (EA) can promote white adipose tissue (WAT) browning to counter obesity. But the mechanism was still not very clear.AimIn this study, we aim to study the effect of EA on promoting inguinal WAT (iWAT) browning and its possible mechanism.MethodThree-week-old rats were randomly divided into a normal diet (ND) group and a high-fat diet (HFD) group. After 10 weeks, the HFD rats were grouped into HFD + EA group and HFD control group. Rats in the EA group were electro-acupunctured for 4 weeks on Tianshu (ST25) acupoint under gas anesthesia with isoflurane, while the rats in HFD group were under gas anesthesia only. Body weight and cumulative food intake were monitored, and H&E staining was performed to assess adipocyte area. The effect of EA on WAT was assessed by qPCR, immunoblotting, immunoprecipitation and Co-immunoprecipitation. Mitochondria were isolated from IWAT to observe the expression of mitochondrial transcription factor A (TFAM).ResultsThe body weight, WAT/body weight ratio and cumulative food consumption obviously decreased (P < 0.05) in the EA group. The expressions of brown adipose tissue (BAT) markers were increased in the iWAT of EA rats. Nevertheless, the mRNA expressions of WAT genes were suppressed by 4-week EA treatment. Moreover, EA increased the protein expressions of SIRT-1, PPARγ, PGC-1α, UCP1 and PRDM16 which trigger the molecular conversion of iWAT browning. The decrease of PPARγ acetylation was also found in EA group, indicating EA could advance WAT-browning through SIRT-1 dependent PPARγ deacetylation pathway. Besides, we found that EA could activate AMPK to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis.ConclusionIn conclusion, EA can remodel WAT to BAT through inducing SIRT-1 dependent PPARγ deacetylation, and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. This may be one of the mechanisms by which EA affects weight loss.

Background. Cancer-induced bone pain (CIBP) is a highly prevalent symptom, which afflicts vast majority of patients who suffer from cancer. The current treatment options failed to achieve satisfactory effect and the side effects were prominent. Recent randomized controlled trials (RCTs) of animal demonstrate the benefit of acupuncture for CIBP. We sought to determine if the pooled data from available RCTs supports the use of acupuncture for CIBP. Methods. A literature search for randomized controlled trials was conducted in six electronic databases from inception to May 31, 2019. Meta-analysis was performed with Review Manager 5.3 software; the publication bias was assessed by Stata 12.0 software. We used random effects model for pooling data because heterogeneity is absolute among studies to some extent. Results. Twenty-four trials were included in the review, of which 12 trials provided detailed data for meta-analyses. Preliminary evidence indicates that compared to wait list/sham group, acupuncture was effective on increasing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Compared to medicine, acupuncture was less effective on PWT, but as effective as medicine on PWL. Acupuncture can reinforce medicine’s effect on PWT and PWL. Compared to the control group, acupuncture was superior to increase body weight (BW), decrease spinal cord glial fibrillary acidic protein (GFAP), and interleukin-1β (IL-1β). Furthermore, some studies showed acupuncture delay or partially reverse morphine tolerance. Three studies found acupuncture has no effect on PWT, but 2 of them found acupuncture could enhance small dose of Celebrex’s effect on CIBP. Conclusions. Acupuncture was superior to wait list/sham acupuncture on increasing PWT and has no less effect on increasing PWL compared to medicine; acupuncture improved the efficacy of drugs, increased the CIBP animals’ body weight, and decreased their spinal cord GFAP and IL-1β. High-quality studies are necessary to confirm the results.

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically, but the mechanism is unclear. Interleukin-10 (IL-10), which is produced by regulatory T (Treg) cell, is a key anti-inflammatory cytokine for relieving inflammatory pain. Therefore, the aim of this study is to investigate whether EA could inhibit CFA-induced pain and attenuate inflammation progression by regulating the activation of immunocyte and inducing the expression of IL-10. In this study, mice were treated with EA (2/100 Hz, 2 mA) for five consecutive days after 1 day of CFA injection. The behavioral tests were measured and analyzed after the daily EA treatment; then, hind paw, spinal cord, and spleen tissues were prepared for assessment. The results showed that EA treatment significantly increased the mechanical threshold and thermal latency after CFA injection and boosted the expression of IL-10 in paw and spinal cord tissues. EA treatment promoted Treg cells; suppressed macrophage and neutrophils cells; reduced the expression of IL-1β, NLRP3, and TNF-α; and ultimately relieved inflammatory pain. The findings suggested that the analgesic and anti-inflammatory effect of EA treatment could be partially associated with suppression of pro-inflammatory cytokines mediated by induction of IL-10.

Myocardial ischemia/reperfusion (I/R) is an important complication of reperfusion therapy for myocardial infarction, and trimetazidine is used successfully for treatment of ischemic cardiomyopathy by regulating mitochondrial function. Moreover, electroacupuncture (EA) preconditioning was demonstrated to be cardioprotective in both in vivo rodent models and in patients undergoing heart valve replacement surgery. However, the mechanisms have not been well elucidated. Mitophagy, mediated by the mTORC1-ULK1-FUNDC1 (mTOR complex 1-unc-51-like autophagy-activating kinase 1-FUN14 domain-containing 1) pathway, can regulate mitochondrial mass and cell survival effectively to restrain the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we hypothesized that EA preconditioning ameliorated MIRI via mitophagy. To test this, rapamycin, an mTOR inhibitor, was used. The results showed that EA preconditioning could reduce the infarct size and risk size, and decrease the ventricular arrhythmia score and serum creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in MIRI rats. Moreover, it also attenuated MIRI-induced apoptosis and mitophagy accompanied by elevated mTORC1 level and decreased ULK1 and FUNDC1 levels. However, these effects of EA preconditioning were blocked by rapamycin, which aggravated MIRI, reduced adenosine triphosphate (ATP) production, and antagonized infarct size reduction. In conclusion, our results indicated that EA preconditioning protected the myocardium against I/R injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway.

The pathological process and mechanism of myocardial ischemia (MI) is very complicated, and remains unclear. An integrated proteomic-metabolomics analysis was applied to comprehensively understand the pathological changes and mechanism of MI. Male Sprague-Dawley rats were randomly divided into a mock surgery (MS) group and an MI group. The MI model was made by ligating the left anterior descending coronary artery, twenty-four hours after which, echocardiography was employed to assess left ventricular (LV) function variables. Blood samples and left ventricular tissues were collected for ELISA, metabolomics and proteomics analysis. The results showed that LV function, including ejection fraction (EF) and fractional shortening (FS), was significantly reduced and the level of cTnT in the serum increased after MI. iTRAQ proteomics showed that a total of 169 proteins were altered including 52 and 117 proteins with increased and decreased expression, respectively, which were mainly involved in the following activities: complement and coagulation cascades, tight junction, regulation of actin cytoskeleton, MAPK signaling pathway, endocytosis, NOD-like receptor signaling pathway, as well as phagosome coupled with vitamin digestion and absorption. Altered metabolomic profiling of this transition was mostly enriched in pathways including ABC transporters, glycerophospholipid metabolism, protein digestion and absorption and aminoacyl-tRNA biosynthesis. The integrated metabolomics and proteomics analysis indicated that myocardial injury after MI is closely related to several metabolic pathways, especially energy metabolism, amino acid metabolism, vascular smooth muscle contraction, gap junction and neuroactive ligand-receptor interaction. These findings may contribute to understanding the mechanism of MI and have implication for new therapeutic targets.

Colorectal cancer, a malignant neoplasm that occurs in the colorectal mucosa, is one of the most common types of gastrointestinal cancer. Colorectal cancer has been studied extensively, but the molecular mechanisms of this malignancy have not been characterized. This study identified and verified core genes associated with colorectal cancer using integrated bioinformatics analysis. Three gene expression profiles (GSE15781, GSE110223, and GSE110224) were downloaded from the Gene Expression Omnibus (GEO) databases. A total of 87 common differentially expressed genes (DEGs) among GSE15781, GSE110223, and GSE110224 were identified, including 19 upregulated genes and 68 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for common DEGs using clusterProfiler. These common DEGs were significantly involved in cancer-associated functions and signaling pathways. Then, we constructed protein-protein interaction networks of these common DEGs using Cytoscape software, which resulted in the identification of the following 10 core genes: SST, PYY, CXCL1, CXCL8, CXCL3, ZG16, AQP8, CLCA4, MS4A12, and GUCA2A. Analysis using qRT-PCR has shown that SST, CXCL8, and MS4A12 were significant differentially expressed between colorectal cancer tissues and normal colorectal tissues (P<0.05). Gene Expression Profiling Interactive Analysis (GEPIA) overall survival (OS) has shown that low expressions of AQP8, ZG16, CXCL3, and CXCL8 may predict poor survival outcome in colorectal cancer. In conclusion, the core genes identified in this study contributed to the understanding of the molecular mechanisms involved in colorectal cancer development and may be targets for early diagnosis, prevention, and treatment of colorectal cancer.

Aims Electro-acupuncture pretreatment (EAP) plays a protective role in myocardial ischemia (MI) injury. However, the underlying mechanism remains unclear. A growing body of evidence suggests postinfarction inflammatory response directly affects the remodeling of ventricular function. The purpose of this study was to investigate whether EAP alleviates MI through NLRP3 inflammasome inhibition. Materials and methods We constructed an AMI model by ligating the left anterior descending (LAD) coronary artery after 3 days of EAP with C57BL/6 mice. Echocardiography and TTC staining were employed to evaluate cardiac function and infarct size after 24 h of ischemia. HE staining and immunohistochemistry were employed to determine inflammatory level. Then, inflammasome activation was detected by western blotting, and macrophage polarization and neutrophil infiltration were observed by flow cytometry. Key findings Our preliminary findings showed that EAP reduced the infarct area and increased fractional shortening (FS) and ejection fraction (EF) and decreased the degree of inflammation after AMI injury. Meanwhile, EAP inhibited the expression of NLRP3, cleaved caspase-1 and IL-1β in ischemia myocardial tissue, companied by inhibiting the expression of F4/80+, CD11b+, CD206low macrophages and activated M2 macrophage, and decreasing Ly-6G+CD11b+ neutrophils in ischemia myocardial and spleen tissue. Significance EAP inhibits the activation of NLRP3 inflammasome, promotes M2 polarization of macrophages and reduces the recruitment of neutrophils in damaged myocardium, thereby decreases the infarct size and improves the cardiac function.

Objective: This study investigated the influence of electroacupuncture (EA) and its potential underlying mechanisms on adipose tissue in obese mice. Methods: Three-week-old male C56BL/6 mice were randomly divided to feed or not to feed high-fat diet (HFD), named HFD group and chow diet (CD) group, respectively. After 12 weeks, CD and HFD mice were randomly divided into two groups, respectively, to receive or not receive EA for 4 weeks. Body weight (BW) was monitored. Intraperitoneal glucose tolerance test and metabolic chamber recordings were performed. Blood samples and adipose tissue were collected for the analysis of leptin, triglyceride levels, and fat browning-related proteins. Results: EA significantly reduced food intake, BW, and white adipose tissue (WAT)/BW ratio; decreased the adipocyte size and serum concentrations of triglyceride (TG) and cholesterol; and increased oxygen consumption in HFD mice. Compared with the CD mice, the HFD mice had elevated fasting serum glucose level and impaired glucose tolerance; however, these parameters were decreased by EA treatment. Meanwhile, EA promoted the protein and mRNA expressions of UCP1, PRDM16, and PGC-1α in adipose tissue, and activated sympathetic nerves via p-TH, A2AR, and β3AR in white adipose tissue. Conclusions: EA reduced food intake, BW, TG, and cholesterol, and improved glucose tolerance in HFD mice. This ameliorative effect of EA on obesity-related symptoms associated with its promoted adipose tissue plasticity via activating sympathetic nerves.

Muscle atrophy refers to a decrease in the size of muscles in the body, occurs in certain muscles with inactivity in many diseases and lacks effective therapies up to date. Natural products still play an important role in drug discovery. In the present study, derivatives of a natural product, oleanolic acid, were screened with myoblast differentiation and myotube atrophy assays, respectively. Results revealed that one of the derivatives, HA-19 showed the most potent anti-muscle atrophy activity, and was used for further studies. We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. The interesting thing was that HA-19 also suppressed protein degradation to prevent myotube atrophy by down-regulating negative growth factors, FoxO1, MuRF1 and Atrogin-1. The results were also supported by puromycin labelling and protein ubiquitination assays. These data revealed that HA-19 possessed a "dual effect" on inhibition of muscle atrophy. In disuse-induced muscle atrophy mice model, HA-19 treatment significantly increased the weights of bilateral tibialis anterior (TA), gastrocnemius (Gastroc.), quadriceps (Quad.), suggesting the effectiveness of HA-19 to remit disuse-induced muscle atrophy. Our finding demonstrated that HA-19 has a great potential as an inhibitor or lead compound for the anti-muscle atrophy drug discovery.

Electroacupuncture (EA) has been developed on the basis of traditional Chinese acupuncture. EA can suppress craving in opioid addicts and opioid-seeking responses in rodents. However, the molecular mechanism of EA on the rewarding properties of morphine and craving responses is not known. Here, we have applied a conditioned place preference paradigm in mice to measure morphine-induced rewarding effects along with EA treatment. Circular RNAs (circRNAs) can function as micro RNA (miRNA) sponges to effectively regulate gene expression levels. CircRNA profiling within the nucleus accumbens (NAc) was performed in EA-treated and sham-treated mice. Following RNAseq, data were analyzed by gene ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) tools. We identified 112 significantly differentially expressed circRNAs, including 51 that were up-regulated and 61 that were down-regulated. Our bioinformatics analyses show that these differentially expressed circRNAs map into pathways that are mainly involved with renin secretion and the cGMP-PKG signaling. We further constructed a circRNA-miRNA network that predicts the potential roles of the differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our secondary sequencing and bioinformatics analysis in the NAc after EA treatment on morphine-induced CPP provides putative novel targets on molecular mechanisms involved in morphine reinforcement and possibly craving.

Objectives. Our previous study has used RNA-seq technology to show that apoptotic molecules were involved in the myocardial protection of electroacupuncture pretreatment (EAP) on the ischemia/reperfusion (I/R) animal model. Therefore, this study was designed to investigate how EAP protects myocardium against myocardial I/R injury through antiapoptotic mechanism.Methods. By using rats with myocardial I/R, we ligated the left anterior descending artery (LAD) for 30 minutes followed by 4 hr of reperfusion after EAP at the Neiguan (PC6) acupoint for 12 days; we employed arrhythmia scores, serum myocardial enzymes, and cardiac troponin T (cTnT) to evaluate the cardioprotective effect. Heart tissues were harvested for western blot analyses for the expressions of pro- and antiapoptotic signaling molecules.Results. Our preliminary findings showed that EAP increased the survival of the animals along with declined arrhythmia scores and decreased CK, LDH, CK-Mb, and cTnT levels. Further analyses with the heart tissues detected reduced myocardial fiber damage, decreased number of apoptotic cells and the protein expressions of Cyt c and cleaved caspase 3, and the elevated level of Endo G and AIF after EAP intervention. At the same time, the protein expressions of antiapoptotic molecules, including Xiap, BclxL, and Bcl2, were obviously increased.Conclusions. The present study suggested that EAP protected the myocardium from I/R injury at least partially through the activation of endogenous antiapoptotic signaling.

Acupuncture is considered to be a promising alternative therapy for depression. Nevertheless, up to now, it remains controversial on the effects exerted by acupuncture on behavioral changes in depression models. Consequently, it’s necessary to develop a systematic review and meta-analysis to assess the effect of acupuncture for model rats of depression. Ultimately, 90 studies involving 1861 models were identified. Behavioral indicators including the number of crossings (NC) and the number of rearings (NR) in open field test (OFT), the capacity of sucrose intake (CSI) and the rate of sucrose intake (RSI) in sucrose intake test (SIT), final weight (FW) and gain weight (GW) were employed as main outcomes in depression model rats. The pooled results showed that acupuncture had not less effect than western medicine on improving NC, NR, FW, GW, RSI (P > 0.05). However, the CSI improvement was poorer compared with west medicine (P

Aims To study the protective effects of late remote ischaemic preconditioning (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO). Methods and results Mice were exposed to lower limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects. Heart tissues were harvested to determine the cardiomyocytes' anti-apoptotic and survival signaling. When compared with the Stat5fl/fl mice without RIPC, Stat5fl/fl mice with RIPC (Stat5fl/fl+RIPC + I/R) displayed a decreased myocardial IS/LV (16 ± 1.5 vs. 30.1 ± 3.1%, P < 0.01; IS/ area at risk (AAR), 42.2 ± 3.5 vs. 69.2 ± 4.9%, P < 0.01), a reduced cardiomyocyte apoptotic rate (2.1 ± 0.37 vs. 5.5 ± 0.53%, P < 0.01), and lower creatine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels. To the contrary, the Stat5-cKO mice (Stat5fl/fl; Tnnt2Cremice with Doxycycline treatment for 7 days) did not exhibit any effect of RIPC-induced cardioprotection. Activation of STAT5 protein was significantly higher in the Stat5fl/fl+RIPC + I/R group than in the Stat5fl/fl+I/R group, while there was no significant difference between the Stat5-cKO + RIPC + I/R and the Stat5-cKO + I/R group. Further analyses with heart tissues detected decreased protein expressions of cytochrome c (Cyt c) and cleaved Caspase-3 in the Stat5fl/fl+RIPC + I/R mice, along with increased anti-apoptotic molecules, including B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma-2 (Bcl-2); such changes were not noted in the Stat5-cKO + RIPC + I/R mice. Additionally, RIPC increased cardiac hypoxia inducible factor-1 (HIF-1α) and interleukin-10 (IL10) protein levels and caused activation of AKT, phosphatidylinositol 3 kinase (PI3K), and vascular endothelial growth factor in the heart of the Stat5fl/fl mice. However, these changes were completely inhibited by the absence of Stat5. Conclusions These results suggest that RIPC-induced late cardioprotection against myocardial I/R injury is Stat5-dependent and is correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling.

Acupuncture is reported to be effective in treating obesity related illnesses, but its mechanism is still unclear. To investigate this mechanism we applied electro-acupuncture (EA) in a mouse model of obesity and used RNA-seq to identify molecular consequences. Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity. Acupuncture, in turn, reduced body weight and the ratio of epididymal white adipose tissue (Epi-WAT) to body weight, and it also decreased plasma concentrations of glucose, triglyceride, and cholesterol. In addition, EA increased cold endurance of Stat5NKO obese mice. EA reversed altered gene expressions in the hypothalamus and Epi-WAT, especially in the hypothalamus in Stat5NKO obese mice. This study provides, for the first time, insight into genomic networks of obesity and their modulation by electro-acupuncture, which in turn reveals potential mechanisms that explain acupuncture-induced weight-loss.

Background: Autophagy has increasingly been recognized as playing an essential role in the pathogenesis of myocardial ischemia reperfusion injury (MIRI). Moxibustion, a form of heat therapy commonly used in traditional Chinese medicine (TCM), has been shown to exhibit cardioprotective effects. However, whether the cardioprotective effect of moxibustion is related to the regulation of autophagy remains unknown. This study aimed to investigate the possible mechanism underlying the cardioprotective effect of moxibustion preconditioning at PC6 on MIRI by measuring the expressions of proteins involved in the regulation of autophagy. Methods: Male Sprague-Dawley rats were randomly divided to receive moxibustion preconditioning or autophagy inhibitor 3-Methyladenine (3-MA) intervention. Then the MIRI model was established by ligating the left anterior descending (LAD) coronary artery for 30 minutes followed by reperfusion for 4 hours. After 4 hours of reperfusion, the myocardial infarction area was assessed using Evans blue and TTC staining, and cTnT and lactate dehydrogenase (LDH) levels in the serum were determined by ELISA. Hematoxylin and eosin (H&E) staining was performed for morphological evaluation of ventricular tissues. Expressions of autophagy components Beclin 1, Bcl-2, and Akt were assessed using quantitative real-time PCR, immunohistochemistry (IHC) and western blot. Results: Moxibustion preconditioning significantly reduced the necrotic area and the levels of cTnT and LDH were similar to the 3-MA intervention, also attenuated morphological alterations were induced by MIRI. Simultaneously, the mRNA and protein expressions of Beclin 1 and Akt were up-regulated, while those of Bcl-2 were down-regulated by MIRI. Moxibustion preconditioning and 3-MA intervention reversed MIRI-induced changes in Beclin 1, Akt, and Bcl-2 expressions. Conclusions: Moxibustion preconditioning at PC6 can attenuate myocardial injury for MIRI in a similar way to 3-MA intervention. This cardioprotective effect of moxibustion preconditioning may be mediated by modulating autophagy via regulation of Beclin 1, Bcl-2 and Akt.

Background Memory loss is the most prominent symptoms of brain aging, but there is currently no evidence-based treatment strategy. Acupuncture has been widely used in China and the effectiveness for improving learning and memory has been mentioned in previous studies. We conducted this systematic review and meta-analysis to evaluate the effectiveness of acupuncture for improving learning and memory in animal experiments. Methods We searched Pubmed, Embase, Ovid Medline(R), the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and Wanfang data Information Site to collect studies published up to December 2015. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measure is Morris water maze. A meta-analysis was conducted according to the Cochrane systematic review method by using RevMan 5.3 software. Results Forty-two studies involving 944 animals were included. The quality score of the studies ranged from 2 to 8, with a mean of 5.3. Meta-analysis results showed that 24 studies reported significant effect of acupuncture for decreasing escape latency (−3.00, 95 % CI: −3.78 ~ −2.23, P

We investigate the effect of electroacupuncture (EA) on protecting the weight gain side effect of rosiglitazone (RSG) in type 2 diabetes mellitus (T2DM) rats and its possible mechanism in central nervous system (CNS). Our study showed that RSG (5 mg/kg) significantly increased the body weight and food intake of the T2DM rats. After six-week treatment with RSG combined with EA, body weight, food intake, and the ratio of IWAT to body weight decreased significantly, whereas the ratio of BAT to body weight increased markedly. HE staining indicated that the T2DM-RSG rats had increased size of adipocytes in their IWAT, but EA treatment reduced the size of adipocytes. EA effectively reduced the lipid contents without affecting the antidiabetic effect of RSG. Furthermore, we noticed that the expression of PPARγgene in hypothalamus was reduced by EA, while the expressions of leptin receptor and signal transducer and activator of transcription 3 (STAT3) were increased. Our results suggest that EA is an effective approach for inhibiting weight gain in T2DM rats treated by RSG. The possible mechanism might be through increased levels of leptin receptor and STAT3 and decreased PPARγexpression, by which food intake of the rats was reduced and RSG-induced weight gain was inhibited.