Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

The antimicrobial peptide YD attenuates inflammation via miR-155 targeting CASP12 during liver fibrosis.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155-Casp12-NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Protective effect of peptide DR8 on bleomycin-induced pulmonary fibrosis by regulating the TGF-ß/MAPK signaling pathway and oxidative stress.

Pulmonary fibrosis (PF) is a fatal and irreversible lung disease that eventually causes respiratory failure, lung dysfunction and death. The peptide DHNNPQIR-NH2 (DR8) has been reported to possess potent antioxidant activity, and an imbalance of oxidation/antioxidation is a crucial mechanism that causes PF. Here, we studied the ability of DR8 to improve PF and further explored the pathway in which DR8 plays a critical role. We found that after prophylactic or therapeutic treatment with DR8, fibrosis-associated indices, including marker proteins, proinflammatory cytokines and profibrogenic cytokines, were significantly downregulated. Importantly, DR8 could reduce bleomycin-induced pathological changes and collagen deposition, especially collagen I content. Furthermore, DR8 prominently upregulated nonenzymatic antioxidants and enzymatic antioxidants. Consistent with the in vivo results, we observed that DR8 significantly inhibited the proliferation and reactive oxygen species (ROS) generation of A549 cells and NIH3T3 cells stimulated with transforming growth factor-ß1 (TGF-ß1), as well as decreased NADPH oxidase 4 (NOX4) levels under the same conditions. Moreover, DR8 reversed the TGF-ß1-induced upregulation of phosphorylated ERK1/2 and p38 MAPK in cells and the bleomycin-induced upregulation of these indices in mice. Our results indicate that DR8 could prevent and treat PF by reducing oxidative damage and suppressing the TGF-ß/MAPK pathway. Because of the high efficiency and low toxicity of DR8, we consider that DR8 could be a candidate drug for PF, and our studies establish a foundation for the development of a lead compound to be used as a therapy for fibrosis-related diseases.

Cupping Therapy for Knee Osteoarthritis: A Synthesis of Evidence.

BACKGROUND: This systematic review was aimed to evaluate the efficacy and safety of cupping therapy for treating patients with knee osteoarthritis (KOA). METHODS: The following databases were searched from their inception until June 2017: the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and 4 Chinese databases (Wan Fang Data, Chinese Biomedical Literature Database (CBM), VeiPu, and China National Knowledge Infrastructure (CNKI)). Randomized controlled trials (RCTs) assessing the effects of cupping therapy on KOA were included in this systematic review. A quantitative synthesis of the RCTs was conducted using RevMan 5.3 software. Study selection and data extraction and validation were performed independently by 2 reviewers. Cochrane criteria for risk of bias were used to assess the methodological quality of the trials. RESULTS: A total of 5 studies met our inclusion criteria. We analyzed the data from these 5 RCTs involving 535 participants. All included studies were judged to be at high risk for bias. Dry cupping therapy plus Western medicine therapy was more effective than Western therapy alone in reducing the pain scores (mean difference (MD) = -1.79, 95% confidence interval (CI) -2.40 to -1.18; p < 0.01). In addition, the study participants in the dry cupping therapy plus Western medicine therapy group showed significantly greater improvements in the pain (MD = -0.73, 95% CI -1.61 to -0.41; p < 0.01), stiffness (MD = -0.94, 95% CI -1.30 to -0.58; p < 0.01), and physical function (MD = -10.07, 95% CI -13.45 to -6.69; p < 0.01) domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to participants in the Western medicine therapy group. Moreover, when compared with Western medicine therapy alone, a meta-analysis of 4 RCTs suggested statistically significant favorable effects of wet cupping therapy plus Western medicine on the Lequesne Algofunctional Index (LAI) (MD = -3.44, 95% CI -4.21 to -2.68; p < 0.01). CONCLUSION: There is weak evidence to support the hypothesis that cupping therapy has beneficial effects on reducing the pain intensity and improving the physical function in patients with KOA.

Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-κB signaling pathways in diabetic nephropathy.

INTRODUCTION: Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. MATERIALS AND METHODS: Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). RESULTS: RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. CONCLUSION: RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-κB pathways.