Efficacy and safety of Shugan Jieyu Decoction in the treatment of coronary heart disease complicated with depression.

BACKGROUND: Coronary heart disease combined with depression is 1 of the 2 major diseases affecting physical and mental health. It has become a hot spot at the intersection of psychiatry and internal medicine. Most doctors call double heart medicine, which has a high incidence rate and a low diagnostic rate. Clinical research shows that Shugan Jieyu Decoction (SJD) has a better curative effect, increased safety, and fewer adverse reactions, but it lacks systematic evaluation. This study aims to integrate clinical data through network meta-analysis and provide more evidence-based medical evidence for clinical medication. METHODS: We searched 8 electronic databases: China knowledge network database, Wanfang, VIP, SinoMed, PubMed, Embase, WebofScience, Cochrane Library, and selected 22 randomized controlled trials from January 2012 to January 2022. The common primary endpoint was the relief of angina pectoris and the improvement of depression. Two researchers used Endnote9.1 software to conduct literature screening and information extraction according to the developed nano-passage standard, used Cochrane collaborative tool to evaluate the bias risk in the experiment, and then used RevMan5.3 software to assess the literature and data analysis synthesis. RESULTS: In 1908 patients with coronary heart disease and depression, the total effective rate of SJD in the treatment of angina pectoris was 3.49 (95% confidence interval, 1.93-6.29), as well as the network meta-analysis of improving depressive symptoms, anxiety, depression scores (SAS, SDS) and quality of life scores (HAMD), and reducing the indicators related to CPR and homocysteine. CONCLUSION: The analysis of this study shows that SJD can reduce the frequency of angina pectoris in patients with coronary heart disease and depression, alleviate anxiety and depression, provide a reference basis for clinical treatment, and select more effective intervention therapy.

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination.

Cold atmospheric plasma (CAP) is selective against many cancers with little side effect, yet its molecular mechanism remains unclear. Through whole transcriptome sequencing followed by assays in vitro, in vivo and using clinical samples, we propose CAP as a promising onco-therapy targeting cancer stemness via the AQP3/FOXO1 axis. CAP-generated reactive species penetrated cells via AQP3 and suppressed RPS6KA3, a shared kinase of AQP3 and FOXO1. Reduced AQP3-19Y phosphorylation suppressed SCAF11-mediated AQP3-5K K48-ubiquitination that led to sabotaged FOXO1 stability. Inhibited FOXO1 phosphorylation retarded its regulatory activities in maintaining cancer stemness including ALDH1 and IL6. Enhanced anti-cancer efficacy was observed through combining CAP with Atorvastatin in vitro and in vivo. We propose CAP as a 'selective' onco-therapeutic against cancer stemness, with the AQP3/FOXO1 axis being one molecular mechanism. We report SCAF11 as an E3 ubiquitin ligase of both AQP3 and FOXO1, identify AQP3-5K as an AQP3 K48-ubiquitination site, and emphasize the essential role of AQP3-19Y in this process. We reposition Atorvastatin into the onco-therapeutic portfolio by synergizing it with CAP towards enhanced efficacy. We anticipate the efficacy of CAP in targeting malignancies of high stemness alone or as an adjuvant therapy towards the hope of ultimate cancer cure.

Enriched environment enhances NK cell maturation through hypothalamic BDNF in male mice.

Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti-obesity and anti-cancer phenotypes that are associated with enhanced adaptive immunity and are mediated by brain-derived neurotrophic factor (BDNF). Natural killer (NK) cells have anti-cancer and anti-viral properties, and their absence or depletion is associated with inferior clinical outcomes. In this study, we investigated the effects of EE on NK cell maturation following their depletion. Mice living in EE displayed a higher proportion of NK cells in the spleen, bone marrow, and blood, compared to those living in the standard environment (SE). EE enhanced NK cell maturation in the spleen and was associated with upregulation of BDNF expression in the hypothalamus. Hypothalamic BDNF overexpression reproduced the EE effects on NK cell maturation in secondary lymphoid tissues. Conversely, hypothalamic BDNF knockdown blocked the EE modulation on NK cell maturation. Our results demonstrate that a bio-behavior intervention enhanced NK cell maturation and was mediated at least in part by hypothalamic BDNF.

Efficacy and safety of Tripterygium wilfordii Hook F preparations for the treatment of Crohn disease: A systemic review and meta-analysis protocol.

BACKGROUND: Crohn disease (CD) is associated with substantial healthcare related costs and impairment of quality of life. Tripterygium wilfordii Hook F (TwHF) is proved to be effective for CD in animal and human. However, there is no systemic review and meta-analysis regarding the clinical efficacy and safety of TwHF preparation for the treatment of CD. METHODS: Six electronic databases (Medline, EMBASE, Cochrane database, Chinese National Knowledge Infrastructure, Wanfang Database and Chongqing VIP Database) will be searched for eligibility studies. Data from the included studies will be extracted and the quality of studies will be assessed. Data synthesis will be performed using Review Manager software. Sensitivity analysis and publication bias assessment will also be carried out. RESULTS: This systemic review and meta-analysis will provide synthesized result of clinical efficacy and safety of TwHF preparation for the treatment of CD. CONCLUSION: This research will determine the clinical efficacy and safety of TwHF preparation for the treatment of CD.Registration: PROSPERO CRD42019127893.

Coffee consumption and risk of pancreatic cancer: a systematic review and dose-response meta-analysis.

The association between coffee consumption and pancreatic cancer risk has been extensively studied; however, there is no consistent conclusion. Therefore, this meta-analysis study sought to evaluate dose-response relationship between them. A search was conducted using the PubMed and Web of Science databases. Thirteen high-quality cohort studies were identified, involving in 959,992 study participants and 3831 pancreatic cancer cases. Comparing the highest with lowest categories of coffee intake, the pooled relative risk (RR) was 1.08 (95% CI 0.94-1.25). For dose-response analysis, no evidence of a nonlinear dose-response association between coffee consumption and pancreatic cancer (p for nonlinearity =0.171) was found. The risk of pancreatic cancer was increased by 5.87% (RR =1.06, 95% CI 1.05-1.07) with the increment of one cup/day. Coffee consumption was identified to be related with the increasing risk of pancreatic cancer in a dose-response manner. Nevertheless, further mechanistic studies are needed to clarify the concerned issues.

Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?

Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin's principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose-response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on 'more is better'. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.

Loss of free fatty acid receptor 2 enhances colonic adenoma development and reduces the chemopreventive effects of black raspberries in ApcMin/+ mice.

We previously showed that black raspberries (BRBs) have beneficial effects in human colorectal cancer and a mouse model of colorectal cancer (ApcMin/+). The current study investigated the role of free fatty acid receptor 2 (FFAR2) in colon carcinogenesis and whether the FFAR2 signaling pathway contributes to BRB-mediated chemoprevention in mice. FFAR2 (also named GPR43) is a member of the G-protein-coupled receptor family that is expressed in leukocytes and colon. ApcMin/+ and ApcMin/+-FFAR2-/- mice were given a control diet or the control diet supplemented with 5% BRBs for 8 weeks. FFAR2 deficiency promoted colonic polyp development, with 100% incidence and increased polyp number and size. The ApcMin/+ mice developed colonic tubular adenoma, whereas the ApcMin/+-FFAR2-/- mice developed colonic tubular adenoma with high-grade dysplasia. FFAR2 deficiency also enhanced the cAMP-PKA-CREB-HDAC pathway, downstream of FFAR2 signaling, and increased activation of the Wnt pathway, and raised the percentage of GR-1+ neutrophils in colonic lamina propria (LP) and increased infiltration of GR-1+ neutrophils into colonic polyps. BRBs suppressed colonic polyp development and inhibited the cAMP-PKA-CREB-HDAC and Wnt pathways in the ApcMin/+ mice but not the ApcMin/+-FFAR2-/- mice. They also increased the percentage of GR-1+ neutrophils and cytokine secretion in colonic LP and decreased the infiltration of GR-1+ neutrophils and IL-1ß expression in colon polyps of ApcMin/+ mice but not ApcMin/+-FFAR2-/- mice. These results suggest that loss of FFAR2 drives colon tumorigenesis and that BRBs require functional FFAR2 to be chemopreventive. BRBs have the potential to modulate the host immune system, thereby enhancing the antitumor immune microenvironment.

Biotherapy for autoimmune liver diseases.

Autoimmune liver diseases are chronic inflammatory conditions leading to an etiologically undefined immunemediated attack aimed at hepatocytes and the biliary epithelium. Drugs used in autoimmune liver disease such as ursodeoxycholic acid, prednisolone and azathioprine are not effective in all patients, therefore, new therapeutic approaches are needed for autoimmune liver diseases that are refractory to standard therapy. Biotherapy is a thriving area of research and development, and is used in the treatment of chronic autoimmune liver diseases. However, to date, there is no clinically validated standard biotherapy for autoimmune liver diseases. Thus, future clinical trials are required to evaluate the effectiveness and safety of biotherapy before this approach can be used in routine clinical practice for the therapy of autoimmune liver diseases. This article provides an overview of emerging biotherapy for autoimmune liver diseases.

Effect of rosuvastatin on ROCK activity, endothelial function, and inflammation in Asian patients with atherosclerosis.

BACKGROUND: HMG-CoA reductase inhibitors (statins) inhibit cholesterol biosynthesis, and also decrease the formation of isoprenoid intermediates required for the activation of Rho kinase (ROCK) pathway. ROCK pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis. It has been implicated that inhibition of ROCK can reverse vascular dysfunction in humans with atherosclerosis. However, it is not clear whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis. METHODS: We treated 40 subjects with stable atherosclerosis with rosuvastatin 10 mg/day, or rosuvastatin 40 mg/day for 28 days in a randomized, double-blinded study. We assessed the change in the lipid levels, C-reactive protein (CRP), ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statins therapy. RESULTS: Treatment with rosuvastatin 10 mg and 40 mg significantly reduced LDL cholesterol by 43.2% to 55.9% and increased FMD by 29.3% to 42.5% (p<0.05 for both compared with baselines). Both doses inhibited ROCK activity (p<0.05), and the extent of inhibition was greater with rosuvastatin 40 mg compared with 10 mg (p<0.05). Only rosuvastatin 40 mg significantly reduced hsCRP (p<0.05).There was no correlation between changes in ROCK activity and changes in low-density lipoprotein cholesterol (r=0.37, p>0.05 vs. r=0.41, p>0.05) among patients randomized to rosuvastatin 10 mg group or 40 mg group. There was a correlation between ROCK inhibition and change in FMD among patients with rosuvastatin 10 mg therapy (r=0.43, p<0.05), and 40 mg therapy (r=0.54, p<0.05). Correlation was found between changes in ROCK inhibition and changes in CRP in rosuvastatin 40 mg/day group (r=0.47, p<0.05). CONCLUSION: These results demonstrate that high dose rosuvastatin exerts greater effects on LDL-C, ROCK activity, and CRP than low dose rosuvastatin. These findings provide clinical evidence that statins are effective in improving endothelium dysfunction by a cholesterol-independent mechanism in patients with atherosclerosis.

The effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the JAK2/STAT3 signaling pathway.

In this study, we evaluated the effect of curcumin (Cur) post-treatment on isolated perfused rat hearts that had been subjected to a protocol of ischemia and reperfusion injury. We also examined whether the Janus kinase 2 and signal transducer and activator 3 of transcription (JAK2/STAT3) signaling pathway plays a role in the cardioprotective effects of Cur post-treatment. Isolated perfused rat hearts were subjected to 60 min of ischemia, followed by 60 min of reperfusion. The hearts were exposed to 1-µM Cur during the first 10 min of reperfusion in the absence or presence of the JAK kinase-specific inhibitor AG490 (AG, 1 µM). The Cur treatment conferred a cardioprotective effect, and the treated hearts demonstrated an improved post-ischemic cardiac functional recovery, a decreased myocardial infarct size and decreased lactate dehydrogenase release in the coronary flow, a reduced number of apoptotic cardiomyocytes, up-regulation of the anti-apoptotic protein Bcl2 and down-regulation of the pro-apoptotic protein Caspase3. AG blocked the Cur-mediated cardioprotection by inhibiting the JAK2/STAT3 signaling pathway, as reflected by the abrogation of the Cur-induced up-regulation of Bcl2 and down-regulation of Caspase3. The results suggest that Cur post-treatment can attenuate IR injury through the activation of the JAK2/STAT3 signaling pathway, which transmits a survival signal to the myocardium.

IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect.

Multiple myeloma (MM) patients who receive killer cell Ig-like receptor (KIR) ligand-mismatched, T cell-depleted, allogeneic transplantation may have a reduced risk of relapse compared with patients who receive KIR ligand-matched grafts, suggesting the importance of this signaling axis in the natural killer (NK) cell-versus-MM effect. Expanding on this concept, IPH2101 (1-7F9), an anti-inhibitory KIR mAb, enhances NK-cell function against autologous MM cells by blocking the engagement of inhibitory KIR with cognate ligands, promoting immune complex formation and NK-cell cytotoxicity specifically against MM cell targets but not normal cells. IPH2101 prevents negative regulatory signals by inhibitory KIR, whereas lenalidomide augments NK-cell function and also appears to up-regulate ligands for activating NK-cell receptors on MM cells. Lenalidomide and a murine anti-inhibitory NK-cell receptor Ab mediate in vivo rejection of a lenalidomide-resistant tumor. These mechanistic, preclinical data support the use of a combination of IPH2101 and lenalidomide in a phase 2 trial for MM.

Biological phosphorus removal performance and relevant microorganism characteristics of activated sludge in municipal wastewater treatment plants, China.

Municipal wastewater discharge is threatening the ecological security of the local water environment. This study investigated the field process performance and microorganism characteristics of enhanced biological phosphorus removal (EBPR) in municipal wastewater treatment plants (WWTPs) in China. The results showed that three WWTPs met the required criteria of phosphorus for discharge (< or = 1 mg/L), but with a low level of Accumulibacter (6.4 to 3.8%, on average) and a relatively high level of Competibacter (3.2 to 9.1%) in sludge. The phosphorus release and uptake rates were varied from 0.224 to 7.770 mg/gVSS x h and 0.386 to 7.901 mg/gVSSh, respectively. Denitrifying polyphosphate-accumulating organisms were estimated to be 28.2% of the polyphosphate-accumulating organisms. Sludge characteristics (phosphorus release and uptake rates) were positively correlated with the abundance of Accumulibacter and negatively correlated with the proportion of Competibacter. Moreover, the lower the ratio of anaerobic phosphorus/acetate (e.g., 0.496) is, the more abundant the Competibacter would be. Further discussion on an improvement strategy for these WWTPs for EBPR should be comprehensively based on the data of periodic investigations on field operation, sludge activities, and microbial populations.

Improving water management practices to reduce nutrient export from rice paddy fields.

Nitrogen (N) and phosphorus (P) loss from rice paddy fields represents a significant threat to water quality in China. In this project, three irrigation-drainage regimes were compared, including one conventional irrigation-drainage regime, i.e. continuous submergence regime (CSR), and two improved regimes, i.e. the alternating submergence-nonsubmergence regime (ASNR) and the zero-drainage irrigation technology (ZDIT), to seek cost-effective practices for reducing nutrient loss. The data from these comparisons showed that, excluding the nutrient input from irrigation, the net exports of total N and total P via surface field drainage ranged from -3.93 to 2.39 kg ha and 0.17 to 0.95 g ha(-1) under the CSR operation, respectively, while N loss was -2.46 to -2.23 kg ha(-1) and P export was -0.65 to 0.31 kg ha(-1) under the improved regimes. The intensity of P export was positively correlated to the rate of P application. Reducing the draining frequency or postponing the draining operation would shift the ecological role of the paddy field from a nutrient export source to an interception sink when ASNR or the zero-drainage water management was used. In addition, since the rice yields are being guaranteed at no additional cost, the improved irrigation-drainage operations would have economic as well as environmental benefits.

Phosphorus interception in floodwater of paddy field during the rice-growing season in TaiHu Lake Basin.

A field experiment located in TaiHu Lake Basin in China was conducted, by application of superphosphate or a mixture of superphosphate with manure, to elucidate the interception of P export during a typical rice growing season through 'zero-drainage water management' combined with sound irrigation, rainfall forecasting and field drying. P concentrations in floodwater rapidly declined before the first event of field drying, and subsequently tended to return to the background levels. Before the first field drying TPP was the predominant P form in floodwater on fields with no P input, DRP on plots that received superphosphate only, and DOP on plots treated with the mixture of superphosphate and manure. Thereafter TPP became the major form. No P export was found from the paddy fields, but a retention of 0.65kgha(-1), mainly due to soil P sorption. The results recommend the zero-drainage water management for full-scale areas for minimizing P export.

Effect of Agkistroden blomhoffi (mamushi) on the proliferation of human fibroblasts.

OBJECTIVES: The purpose of this study is to investigate the effect of Agkistroden blomhoffi (mamushi) aqueous extract on human patellar tendon cells in vitro, to pharmacologically explain the natural medicine's healing effect on tendon, bone and muscle injuries. DESIGN AND METHODS: Human patellar tendon fibroblasts (HPTF) were incubated in media containing different concentrations of mamushi aqueous extract. Cell proliferation was studied by microscopic observations and total protein, actin, collagen I, and cyclooxygenase-2 (Cox 2) expressions. RESULTS: Mamushi aqueous extract enhanced HPTF proliferation when its concentration was lower than 333 microg/ml. Cells cultured in manushi-containing medium showed developed intercellular structure and increased protein production. However, mamushi extract higher than 500 microg/ml oppressed cell growth. At 667 microg/ml, mamushi induced Cox 2 production, a sign of cytotoxicity. CONCLUSION: A. blomhoffi aqueous extract was found to directly stimulate the proliferation and protein production, particularly collagen I synthesis, of HPTF in a dose-dependent manner.

Effect of Angelica sinensis on the proliferation of human bone cells.

BACKGROUND: Angelica sinensis, an herbal medicine known for its effect to purify blood quality and improve circulation, frequently appears as the main ingredient in prescriptions for bone injuries. Currently, how pharmacologically it contributes to the reformation of bone is unclear. METHODS: The effect of the aqueous extract of Angelica sinensis on bone cells was investigated in vitro for the first time. The human osteoprecursor cells (OPC-1) were incubated in the medium with different concentrations of the aqueous extract of Angelica sinensis and the cell proliferation was studied. RESULTS: When the concentration of Angelica sinensis aqueous extract was <125 microg/ml, the proliferation of OPC-1 was enhanced. However, the proliferation of OPC-1 was inhibited by Angelica sinensis extract with the concentrations >250 microg/ml. Under most treatments, the cells presented very pale expression for cyclooxygenase-2 (Cox 2) protein; slightly intensified band showed at the highest Angelica sinensis concentration, 1.0 mg/ml during the course of culture. CONCLUSION: The aqueous extract of Angelica sinensis was found to directly stimulate the proliferation, alkaline phosphatase (ALP) activity, protein secretion and particularly type I collagen synthesis of OPC-1 at dose-dependent manner.