The efficacy and safety of acupuncture in nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this study was to determine the efficacy and safety of acupuncture treatment (AT) or acupuncture plus conventional medicine (CM) versus CM alone using a meta-analysis of all published randomized controlled trials (RCTs) for nonalcoholic fatty liver disease (NAFLD). METHODS: Eight databases were searched independently from inception to April 30, 2020. RCTs were included if they contained reports on the use acupuncture or the use of acupuncture combined with CM and compared with the use of CM. Summary odds ratio (OR) and 95% confidence intervals (CIs) were used to calculate the overall clinical efficacy. Secondary outcomes, namely aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index, were calculated by mean difference with 95% CIs. RESULTS: After the final screening, 8 RCTs with 939 patients were included. This meta-analysis showed that AT was superior to CM in improving overall clinical efficacy (OR = 3.19, 95% CI: 2.06-4.92, P  < .00001). In addition, AT plus CM could significantly improve overall clinical efficacy compared to treatment with CM alone (OR = 5.11, 95% CI: 2.43-10.75, P  < .0001). Moreover, the benefits were also demonstrated in other outcomes, including alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol indexes. However, AT plus CM could not decrease body mass index levels in comparison with CM. The safety profile of Acupuncture therapy was satisfactory. Taichong, Zusanli, Fenglong, and Sanyinjiao were major acupoints on NAFLD treatment. CONCLUSION: Acupuncture may be effective and safe for treatment of NAFLD. However, due to insufficient methodological quality and sample size, further high-quality studies are needed.

Efficacy and safety of Shenkang injection as adjuvant therapy in patients with diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy is a frequent microvascular complication of diabetes mellitus that causes end-stage renal disease most of the time. In China, Shenkang injection is one of widely used traditional Chinese medicine for treating chronic kidney disease, but its efficacy and safety have not yet been clarified. We will systematically review the current randomized controlled trial (RCT) evidence to summarize the efficacy and safety of Shenkang injection in treating diabetic nephropathy. METHODS: We will search 7 literature databases including PubMed, EMBASE, Cochrane Library, Sinomed, Chinese National Knowledge Infrastructure, Wanfang, and VIP. Two trial registry platforms will also be searched. The time frame of the search will be from the inceptions of the databases to December 31, 2020. RCTs assessing Shenkang injection combined with basic treatments versus basic treatments alone for treating diabetic nephropathy will be included. The risk of bias within the individual RCTs will be evaluated using criteria proposed by the Cochrane Handbook 5.1.0. The primary outcomes to be investigated are glomerular filtration rate and serum creatinine; the secondary outcome will include 24-hour urine albumin excretion rate, blood urea nitrogen, fasting blood glucose, postprandial blood glucose, hemoglobin A1c, total cholesterol, triglyceride, response to treatment, and incidence of adverse events. The effect data of individual RCTs by performing random-effects model meta-analysis. Statistical heterogeneity will be measured by the Cochran Q test and I-squared statistics. Three subgroup analyses, set based on clinical experience, will be performed to explore the sources of heterogeneity. Sensitivity analyses excluding RCTs with high risk of bias and using fixed effect model will be done to test the robustness of the meta-analytic results. Publication bias across included RCTs will be evaluated by funnel plots and Egger test. RESULTS: This study will provide systematic review on the efficacy and safety of Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy by rigorous quality assessment and reasonable data synthesis. The results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This systematic review will provide the best evidence currently on Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy. INPLASY REGISTRATION NUMBER: INPLASY2020110014.

Heat-sensitive moxibustion self-administration in patients in the community with primary hypertension: A protocol for a multi-center, pragmatic, non-randomized trial.

BACKGROUND: Although the efficacy of antihypertensive drugs has been well established for primary hypertension, their effectiveness is always limited by side effects and poor compliance. Heat-sensitive moxibustion is an innovative acupoint stimulation therapy that is promising as a community health care intervention for hypertension. AIMS: This study aims to evaluate the pragmatic effectiveness and safety of heat-sensitive moxibustion self-administration by patients in the community with primary hypertension. METHODS: This study will adopt a multi-center, pragmatic, nonrandomized design. Six hundred patients with primary hypertension will be recruited from 4 communities. Each patient will choose to either receive heat-sensitive moxibustion self-administration + original antihypertensive drugs or maintain their original antihypertensive drugs without heat-sensitive moxibustion for 1 year. EXPECTED OUTCOMES: The primary outcome will be changes in systolic and diastolic blood pressures and the percentage changes in the doses of antihypertensive drugs. The secondary outcomes will be changes in quality of life assessed by a validated patient-reported outcome scale and the levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urinary albumin, and serum creatinine. The proportion of patients with poor compliance with the heat-sensitive moxibustion regimen will also be evaluated as a secondary outcome. The safety of heat-sensitive moxibustion will be considered by analyzing the incidence of all and serious adverse events and their correlation with heat-sensitive moxibustion. DISCUSSION: The findings of this study will provide pragmatic evidence for heat-sensitive moxibustion self-administration in patients in the community with primary hypertension and may also establish an ethical basis for further randomized controlled trials. TRIAL REGISTRATION: The protocol of this trial was registered in ClinicalTrials.gov at May 11, 2020 (No. NCT04381520).

Changes in cerebral glucose metabolism after acupuncture at KI3 in spontaneously hypertensive rats: a positron emission tomography study.

OBJECTIVE: The aim of this study was to explore the effect of acupuncture stimulation at KI3 on brain glucose metabolism in spontaneously hypertensive rats (SHRs). METHODS: Brain glucose metabolism in SHRs after acupuncture stimulation at KI3 was detected using 18F-2-fluorodeoxy-D-glucose positron emission tomography (18F-FDG-PET). SHRs were randomly divided into three groups: no treatment (SHR group); acupuncture at KI3 (KI3 group); and sham acupuncture (Sham group). Wistar Kyoto (WKY) rats were used as a normal blood pressure (BP) control group. Rats were subjected to 10 min of acupuncture once a day for 7 days. BP and positron emission tomography-computed tomography (PET-CT) were measured after the first acupuncture session and after 7 days of treatment. RESULTS: The results showed that BP was lower in the KI3 group than in the SHR group, both 30-60 min after the first acupuncture session and 24-48 h after the 7-day treatment. Compared with the WKY group, the SHR group had lower glucose metabolism in the motor cortex, sensory cortex, basal ganglia, corpus callosum, caudate putamen, and visual cortex. Compared with the untreated/sham-treated SHR control groups, cerebral glucose metabolism was lower in the medulla oblongata, thalamus, dorsal thalamus, orbital cortex, and hypothalamus after acupuncture at KI3, while it was higher in the olfactory cortex and inferior phrenic muscle. CONCLUSION: Our results show that, in SHRs, needling at KI3 reduces high BP, most likely by altering the activation of cerebral regions.

The mechanism of improved intracellular organic selenium and glutathione contents in selenium-enriched Candida utilis by acid stress.

Batch culture of Candida utilis CCTCC M 209298 for the preparation of selenium (Se)-enriched yeast was carried out under different pH conditions, and maximal intracellular organic Se and glutathione (GSH) contents were obtained in a moderate acid stress environment (pH 3.5). In order to elucidate the physiological mechanism of improved performance of Se-enriched yeast by acid stress, assays of the key enzymes involved in GSH biosynthesis and determinations of energy supply and regeneration were performed. The results indicated that moderate acid stress increased the activity of γ-glutamylcysteine synthetase and the ratios of NADH/NAD+ and ATP/ADP, although no significant changes in intracellular pH were observed. In addition, the molecular mechanism of moderate acid stress favoring the improvement of Se-yeast performance was revealed by comparing whole transcriptomes of yeast cells cultured at pH 3.5 and 5.5. Comparative analysis of RNA-Seq data indicated that 882 genes were significantly up-regulated by moderate acid stress. Functional annotation of the up-regulated genes based on gene ontology and the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway showed that these genes are involved in ATP synthesis and sulfur metabolism, including the biosynthesis of methionine, cysteine, and GSH in yeast cells. Increased intracellular ATP supply and more amounts of sulfur-containing substances in turn contributed to Na2SeO3 assimilation and biotransformation, which ultimately improved the performance of the Se-enriched C. utilis.

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy.

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy.

Unraveling the novel anti-osteosarcoma function of coptisine and its mechanisms.

Uncontrolled cell proliferation and robust angiogenesis play critical roles in osteosarcoma growth and metastasis. In this study we explored novel agents derived from traditional Chinese medicinal herbs that potently inhibit osteosarcoma growth and metastasis. Coptisine, an active component of the herb Coptidis rhizoma, markedly inhibited aggressive osteosarcoma cell proliferation. Coptisine induced cell cycle arrest at the G0/G1 phase through downregulation of CDK4 and cyclin D1 expression and effectively suppressed tumor growth in a xenografted mouse model. Coptisine significantly impeded osteosarcoma cell migration, invasion, and capillary-like network formation by decreasing the expression of VE-cadherin and integrin ß3, and diminishing STAT3 phosphorylation. Coptisine significantly elevated blood erythrocyte and hemoglobin levels while still remaining within the normal range. It also moderately increased white blood cell and platelet counts. These data suggest that coptisine exerts a strong anti-osteosarcoma effect with very low toxicity and is a potential anti-osteosarcoma drug candidate.

Jatrorrhizine hydrochloride inhibits the proliferation and neovascularization of C8161 metastatic melanoma cells.

Malignant melanoma is the most aggressive form of skin cancer. Although various antimelanoma approaches have been used in the clinics to treat the disease over the last three decades, none of the drugs significantly prolonged the survival of metastatic melanoma patients; hence, effective drugs against metastatic melanoma are highly desired. In this study, we explored an antimetastatic melanoma agent derived from traditional Chinese medicinal herbs and found that jatrorrhizine hydrochloride (JH), an active component of the traditional Chinese medicinal herb Coptis chinensis, inhibited the proliferation and neovascularization of C8161 human metastatic melanoma cells. JH suppressed C8161 cell proliferation in a dose-dependent manner, with a half-maximal inhibitory concentration of 47.4±1.6 µmol/l; however, it did not induce significant cellular apoptosis at doses up to 320 µmol/l. Mechanistic studies showed that JH-induced C8161 cell cycle arrest at the G0/G1 transition, which was accompanied by overexpression of the cell cycle-suppressive genes p21 and p27 at higher doses. Moreover, JH reduced C8161 cell-mediated neovascularization in vitro and in vivo and impeded the expression of the gene for VE-cadherin, a key protein in tumor vasculogenic mimicry and angiogenesis. Taken together, the effective inhibitory effects of JH on metastatic melanoma cell proliferation and neovascularization with low toxicity suggest that JH is a potential new antimelanoma drug candidate.

Columbamine suppresses the proliferation and neovascularization of metastatic osteosarcoma U2OS cells with low cytotoxicity.

Osteosarcoma is one of the most common malignant bone tumors in children and adolescents. Although extensive efforts have been made in anti-osteosarcoma therapy in recent decades, there are no effective low-toxicity drugs for treating patients with metastatic osteosarcoma. Hence, potent anti-metastatic osteosarcoma drugs are highly desired. In this study, we explored novel small molecular anti-metastatic osteosarcoma agents and found that columbamine (COL), an active component of the herb Coptis chinensis, inhibited the proliferation and neovascularization of metastatic osteosarcoma U2OS cells. COL effectively suppressed U2OS cell proliferation in vitro with an IC(50) of 21.31±0.38µM, with low cytotoxicity. Mechanistic studies revealed that COL induces cell cycle arrest at the G2/M transition, which is associated with attenuating CDK6 gene expression and diminishing STAT3 phosphorylation. COL did not significantly promote U2OS cell apoptosis at any of the dosages tested. Additionally, COL inhibited U2OS cell-mediated neovascularization, which was accompanied by the down-regulation of matrix metalloproteinase (MMP) 2 expression and reduction of cell migration, adhesion, and invasion. Taken together, our data show that COL exerts anti-proliferative and anti-vasculogenic effects on metastatic human osteosarcoma U2OS cells with low toxicity. These results warrant further investigation of COL as a potential anti-osteosarcoma and anti-cancer drug.