Association between the sarcopenia-related traits and Parkinson's disease: A bidirectional two-sample Mendelian randomization study.

OBJECTIVE: To explore the causal association between sarcopenia-related traits and Parkinson's disease by Mendelian randomization (MR) approach. METHODS: A genome-wide association study (GWAS) of sarcopenia-related traits was done at the UK Biobank (UKB). The traits were appendicular lean mass, low hand grip strength (including the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) criteria and usual walking pace. The International Parkinson's Disease Genomics Consortium (IPDGC) gave us GWAS data for Parkinson's disease (PD). We used three different types of MR analyses: including Inverse-variance weighted (IVW), Mendelian randomized Egger regression (MR-Egger), and weighted median methods (both weighted and simple modes). RESULTS: The MR analysis showed that low hand grip strength was negatively associated with the risk of developing Parkinson's disease, including EWGSOP criterion (odds ratio (OR) = 0.734; 95% confidence interval (CI) = 0.575-0.937, P = 0.013) and FNIH criterion (OR = 0.619; 95% CI = 0.419-0.914, P = 0.016), and usual walking pace was also a risk factor for Parkinson's disease (OR = 3.307, 95% CI = 1.277-8.565, P = 0.014). CONCLUSIONS: In European population, low hand grip strength is negatively associated with the risk of developing Parkinson's disease, and usual walking pace is also a risk factor for Parkinson's disease. Further exploration of the potential genetic mechanisms underlying hand grip strength and Parkinson's disease and the potential relationship between walking pace, balance, and falls in Parkinson's patients may help to reduce the burden of sarcopenia and Parkinson's disease.

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism.

Breast cancer (BC) is a serious global challenge, and depression is one of the risk factors and comorbidities of BC. Recently, the research on the comorbidity of BC and depression has focused on the dysfunction of the hypothalamic-pituitary-adrenal axis and the persistent stimulation of the inflammatory response. However, the further mechanisms for comorbidity remain unclear. Epoxide metabolism has been shown to have a regulatory function in the comorbid mechanism with scattered reports. Hence, this article reviews the role of epoxide metabolism in depression and BC. The comprehensive review discloses the imbalance in epoxide metabolism and its downstream effect shared by BC and depression, including overexpression of inflammation, upregulation of toxic diols, and disturbed lipid metabolism. These downstream effects are mainly involved in the construction of the breast malignancy microenvironment through liver regulation. This finding provides new clues on the mechanism of BC and depression comorbidity, suggesting in particular a potential relationship between the liver and BC, and provides potential evidence of comorbidity for subsequent studies on the pathological mechanism.

A meritorious integrated medical regimen for hepatic fibrosis and its complications via the systematic review and meta-analysis for Dahuang Zhechong pill-based therapy.

Background: Hepatic fibrosis is a health challenge due to the absence of satisfactory therapy, especially at the cirrhosis stage. Dahuang Zhechong pill (DHZCP)-based therapy is reportedly a successful treatment for hepatic fibrosis and is even beneficial for the treatment of cirrhosis. Hence, a systematic review and clinical evidence assessment of DHZCP-based therapy should be performed, and clinical recommendations based on its efficacy for the treatment of hepatic fibrosis should be generated. With respect to potential indicators, the comparative value of the hepatic function, spleen thickness, and portal vein internal diameter should be evaluated. Materials and methods: PubMed, the Excerpta Medica Database, the Cochrane Library, the Web of Science, the WanFang Database, the Chinese Scientific Journal Database, and the Chinese National Knowledge Infrastructure database were searched to identify clinical trials. Three subgroup analyses were performed based on the stage of disease, medication use, and the course of treatment. Statistical analyses were performed using Review Manager 5.4. Results: A total of 18 studies including 1,494 patients were evaluated. The DHZCP-based therapy was effective in reducing the plasma levels of hyaluronic acid, and laminin, procollagen III, and IV collagen were also reduced irrespective of the hepatitis stage or the presence of hepatic cirrhosis. Abnormalities in alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin were reversed. A 6-month course of treatment was the most beneficial DHZCP-based therapy regimen. Alanine aminotransferase improvement was more obvious in patients with cirrhosis, and alanine aminotransferase was reduced significantly in patients with hepatic cirrhosis. With respect to pharmacological mechanisms, DHZCP-based therapy could inhibit hepatic stellate cell growth and activation, reduce inflammation, and prevent extracellular matrix formation. Hepatic portal hypertension and splenomegaly were ameliorated significantly in the DHZCP-based therapy group. Conclusion: Dahuang Zhechong pill-based therapy has demonstrated efficacy as a treatment for hepatic fibrosis and cirrhosis. A 6-month course of treatment is the recommended option for DHZCP-based therapy in clinical practice. The combination of DHZCP-based therapy and entecavir is a favorable treatment for hepatic cirrhosis.

Renshen Baidu powder protects ulcerative colitis via inhibiting the PI3K/Akt/NF-κB signaling pathway.

Ulcerative colitis is a chronic and relapsing inflammatory bowel disease without satisfactory therapy available recently. Renshen Baidu powder (RSBDP) is a classic Chinese medicinal formula used since Chinese Song dynasty and has been proven as an effective treatment of ulcerative colitis in clinics. However, the active ingredients and the molecular mechanism have not been fully disclosed. It is imperative to explore the active ingredients and the mechanism of RSBDP. In this study, the potential active components for ulcerative colitis treatment in RSBDP were determined and predicted in silicon, and its molecular mechanisms were also presented, in which the PI3K/Akt/NF-κB signaling pathway was recognized to be vital. Basically, the pharmacodynamics and mechanistic studies of RSBDP for ulcerative colitis were implemented on TNBS-induced experimental rats. The results showed that RSBDP could ameliorate the disease activity index and colon weight, as well as improve colonic shortening and colon histology. In addition, the tumor necrosis factor-α (TNF-α), diamine oxidase, intercellular adhesion molecule-1, and endotoxin in serum were also reduced. It is worth mentioning that the PI3K/Akt/NF-κB signaling pathway was inhibited after RSBDP administration via inhibiting the phosphorylation of proteins. In conclusion, RSBDP effectively ameliorates TNBS-induced colitis rats by inhibiting the PI3K/Akt/NF-κB signaling pathway.

Corrigendum: The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.

[This corrects the article DOI: 10.3389/fmed.2021.766126.].

Efficacy and Safety of Probiotics Combined With Traditional Chinese Medicine for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Background: The combination of probiotics and traditional Chinese medicine (TCM) is a prospective therapy for ulcerative colitis (UC), and its efficacy and safety need to be urgently evaluated. Objective: This study aims to comprehensively assess the efficacy and safety of probiotics combined with TCM for the treatment of UC. Methods: The Pubmed, EMBASE, Cochrane library, China Academic Journals (CNKI), Wan-fang database, Chinese biomedical literature service system (CBM), and Chinese Science and Technology Journals (CQVIP) were searched. Subgroup analysis were designed in accordance with different control drugs, treatment courses, and types of probiotics. The Review Manager software (version 5.4.1) was utilized for statistical analysis. Results: 14 original studies containing 1,154 patients were analyzed and showed that probiotics with TCM was more effective than 5-aminosalicylic acid (5-ASA), probiotics or TCM used individually. Moreover, probiotics combined with TCM could inhibit the intestinal inflammation, reduce the recurrence rate and the incidence of adverse events. The subgroup analysis showed that a mixture of different probiotics was more effective than a single strain. Conclusion: It is suggested that probiotics combined with TCM could effectively control clinical symptoms, inhibit intestinal inflammatory response, and finally slow down the disease progress and reduce the disease recurrence with less adverse events. The mixture of different probiotics used in conjunction with individually tailored TCM is a potential clinical strategy for UC.

Corrigendum: The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphar2021.714287.].

The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.

The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis.

Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens. Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4. Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less. Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events.

Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins.

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)-tyramine conjugates (PGA-Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H2O2/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G'), cross-link density, and mesh size can be tailored by controlling the H2O2/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G') can be tailored from approximately 40 to over 1100 Pa with the increasing H2O2/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitro from the PGA-Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H2O2/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA-Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides.