Roles of focal adhesion proteins in skeleton and diseases.
Chen, S, He, T, Zhong, Y, Chen, M, Yao, Q, Chen, D, Shao, Z, Xiao, G
Acta pharmaceutica Sinica. B. 2023;(3):998-1013
The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.
Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases.
Liu, M, Li, Z, Ouyang, Y, Chen, M, Guo, X, Mazhar, M, Kang, J, Zhou, H, Wu, Q, Yang, S
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023;:154503
BACKGROUND Cardiovascular diseases (CVDs) are among the primary and predominant threats to human health with increasing incidence. Danshen Decoction (DSD) as an adjuvant therapy can benefit CVDs patients by improving clinical efficacy. PURPOSE The purpose of this study was to identify the active components and potential pharmacological mechanisms of DSD by combining mass spectrometry with a network pharmacology strategy and to review the use of DSD in the treatment of CVDs. METHOD First, the composition of DSD was analyzed by ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Second, the network pharmacology method was used to elucidate the underlying material basis and possible pharmacological mechanism of DSD for the treatment of CVDs. Finally, clinical and experimental studies on DSD in the past ten years were retrieved from the PubMed and CNKI database, and the content of these studies was used to summarize the latest progress in DSD treatment of CVDs. OUTCOME A total of 35 compounds were found in DSD by manual identification from the analysis of MS, which may be the material basis for the therapeutic effect of DSD. After taking the intersection of 2086 targets related to CVDs, these 35 compounds are considered to play a role in the treatment of CVDs through 210 targets including signal transducer and activator of transcription 3 (STAT3), sarcoma (SRC) and phosphoinositide-3-kinase regulatory subunit (PIK3R), and a total of 168 signaling pathways were involved in the regulation of CVDs by DSD, including PI3K-AKT signaling pathway, Alzheimer disease, and Rap1 signaling pathway. A total of 29 clinical studies using DSD in the treatment of CVDs were included in the literature review, and these studies showed the positive significance of DSD as adjuvant therapy, while 14 experimental studies included in the literature review also demonstrated the effectiveness of DSD in the treatment of CVDs. CONCLUSION DSD plays a role in the treatment of CVDs through a variety of active ingredients. Large-scale clinical research and more in-depth experimental research will help to further reveal the mechanism of DSD in the treatment of CVDs.
Contrasting relationships between plant-soil microbial diversity are driven by geographic and experimental precipitation changes.
Zuo, X, Sun, S, Wang, S, Yue, P, Hu, Y, Zhao, S, Guo, X, Li, X, Chen, M, Ma, X, et al
The Science of the total environment. 2023;:160654
Soil microbe diversity plays a key role in dryland ecosystem function under global climate change, yet little is known about how plant-soil microbe relationships respond to climate change. Altered precipitation patterns strongly shape plant community composition in deserts and steppes, but little research has demonstrated whether plant biodiversity attributes mediate the response of soil microbial diversity to long- and short-term precipitation changes. Here we used a comparative study to explore how altered precipitation along the natural and experimental gradients affected associations of soil bacterial and fungal diversity with plant biodiversity attributes (species, functional and phylogenetic diversity) and soil properties in desert-shrub and steppe-grass communities. We found that along both gradients, increasing precipitation increased soil bacterial and fungal richness in the desert and soil fungal richness in the steppe. Soil bacterial richness in the steppe was also increased by increasing precipitation in the experiment but was decreased along the natural gradient. Plant biodiversity and soil properties explained the variations in soil bacterial and fungal richness from 43 % to 96 % along the natural gradient and from 19 to 46 % in the experiment. Overall, precipitation effects on soil bacterial or fungal richness were mediated by plant biodiversity attributes (species richness and plant height) or soil properties (soil water content) along the natural gradient but were mediated by plant biodiversity attributes (functional or phylogenetic diversity) in the experiment. These results suggest that different mechanisms are responsible for the responses of soil bacterial and fungal diversity to long- and short-term precipitation changes. Long- and short-term precipitation changes may modify plant biodiversity attribute effects on soil microbial diversity in deserts and steppes, highlighting the importance of precipitation changes in shaping relationships between plant and soil microbial diversity in water-limited areas.
Association of fast-food restaurants with overweight and obesity in school-aged children and adolescents: A systematic review and meta-analysis.
Jiang, J, Lau, PWC, Li, Y, Gao, D, Chen, L, Chen, M, Ma, Y, Ma, T, Ma, Q, Zhang, Y, et al
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;(3):e13536
We aimed to explore associations between the accessibility of fast-food restaurants (FFRs) and weight-related outcomes in children and adolescents through a systematic review and meta-analysis of studies. We searched three databases for studies published before October 21, 2022. Study quality was assessed using the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Meta-analysis was performed, and the leave-one-out method was used for sensitivity analysis. A total of 60 studies were included. According to our analysis, FFRs within a smaller buffer radius from residences or that provide unhealthy foods may have a more significant influence on children's and adolescents' weight. Children of younger ages and girls may have a higher possibility of being overweight due to FFRs. Though we could hardly avoid bias, the estimates in low-and middle-income countries (only six studies) are much higher than those in high-income countries (54 studies). More research analyses based on microscope data and individual economic levels are needed. This study yields quantitative results, provides policymakers and urban planners with a theoretical support for building resilient and sustainable human settlements, and promotes the translation of research findings from public health to environmental planning.
Whole-plant foods and their macromolecules: untapped approaches to modulate neuroinflammation in Alzheimer's disease.
Huang, R, Zhu, Z, Wu, Q, Bekhit, AEA, Wu, S, Chen, M, Wang, J, Ding, Y
Critical reviews in food science and nutrition. 2023;(15):2388-2406
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Recently, sustained neuroinflammatory response in microglia and astrocytes has been found to cause the deposition of amyloid beta plaques and the hyperphosphorylation of tau protein, thereby accelerating AD progression. The lipoxin A4-transcription factor nuclear factor-kappa B and mitogen-activated protein kinase pathways have been shown to play important roles in the regulation of inflammatory processes. There is growing research-based evidence suggesting that dietary whole-plant foods, such as mushrooms and berries, may be used as inhibitors for anti-neuroinflammation. The beneficial effects of whole-plant foods were mainly attributed to their high contents of functional macromolecules including polysaccharides, polyphenols, and bioactive peptides. This review provides up-to-date information on important molecular signaling pathways of neuroinflammation and discusses the anti-neuroinflammatory effects of whole-plant foods. Further, a critical evaluation of plants' macromolecular components that have the potential to prevent and/or relieve AD is provided. This work will contribute to better understanding the pathogenetic mechanism of neuroinflammation in AD and provide new approaches for AD therapy.
Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.
Xu, W, Lv, M, Wu, S, Jiang, S, Zeng, Z, Fang, Z, Qian, J, Chen, M, Chen, J, Zhang, J
Cardiovascular drugs and therapy. 2023;(2):363-377
PURPOSE We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.
Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase.
Chen, M, Guo, Z, Sun, J, Tang, W, Wang, M, Tang, Y, Li, P, Wu, B, Chen, Y
Acta pharmaceutica Sinica. B. 2023;(2):765-774
l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 (2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 (3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.
The Bridge Between Ischemic Stroke and Gut Microbes: Short-Chain Fatty Acids.
Fang, Z, Chen, M, Qian, J, Wang, C, Zhang, J
Cellular and molecular neurobiology. 2023;(2):543-559
Short-chain fatty acids (SCFAs) are monocarboxylates produced by the gut microbiota (GM) and result from the interaction between diet and GM. An increasing number of studies about the microbiota-gut-brain axis (MGBA) indicated that SCFAs may be a crucial mediator in the MGBA, but their roles have not been fully clarified. In addition, there are few studies directly exploring the role of SCFAs as a potential regulator of microbial targeted interventions in ischemic stroke, especially for clinical studies. This review summarizes the recent studies concerning the relationship between ischemic stroke and GM and outlines the role of SCFAs as a bridge between them. The potential mechanisms by which SCFAs affect ischemic stroke are described. Finally, the beneficial effects of SFCAs-mediated therapeutic measures such as diet, dietary supplements (e.g., probiotics and prebiotics), fecal microbiota transplantation, and drugs on ischemic brain injury are also discussed.
Perioperative prophylaxis for surgical site infections in pediatric spinal surgery: a systematic review and network meta-analysis.
Shaffer, A, Naik, A, MacInnis, B, Chen, M, Ivankovic, S, Paisan, G, Garst, JR, Hassaneen, W, Arnold, PM
Journal of neurosurgery. Pediatrics. 2023;(1):43-51
OBJECTIVE Postoperative infections in pediatric spinal surgery commonly occur and necessitate reoperation(s). However, pediatric-specific infection prophylaxis guidelines are not available. This network meta-analysis compares perioperative prophylaxis methods including Betadine irrigation, saline irrigation, intrawound vancomycin powder, combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime), Betadine irrigation plus vancomycin powder, and no intervention to determine the most efficacious prevention method. METHODS A systematic review was performed by searching the PubMed, EBSCO, Scopus, and Web of Science databases for peer-reviewed articles published prior to February 2022 comparing two or more infection prophylaxis methods in patients younger than 22 years of age. Data were extracted for treatment modalities, patient demographics, and patient outcomes such as total number of infections, surgical site infections, deep infections, intraoperative blood loss, operative time, follow-up time, and postoperative complications. Quality and risk of bias was assessed using National Institutes of Health tools. A network meta-analysis was performed with reduction of infections as the primary outcome. RESULTS Overall, 10 studies consisting of 5164 procedures were included. There was no significant difference between prophylactic treatment options in reduction of infection. However, three treatment options showed significant reduction in total infection compared with no prophylactic treatment: Betadine plus vancomycin (OR 0.22, 95% CI 0.09-0.54), vancomycin (OR 3.26, 95% CI 1.96-5.44), and a combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime) (OR 0.24, 95% CI 0.07-0.75). P-Score hierarchical ranking estimated Betadine plus vancomycin to be the superior treatment to prevent total infections, deep infections, and surgical site infections (P-score 0.7876, 0.7175, and 0.7291, respectively). No prophylaxis treatment-related complications were reported. CONCLUSIONS The results of this network meta-analysis show the strongest support for Betadine plus vancomycin as a method to reduce infections following pediatric spinal surgery. There was heterogeneity among studies and inconsistent outcome reporting; however, three effective treatment options are identified.
Clinical characteristics of 512 eculizumab-naive paroxysmal nocturnal hemoglobinuria patients in China: a single-center observational study.
Du, Y, Yang, Y, Yang, C, Chen, M, Han, B
Hematology (Amsterdam, Netherlands). 2022;(1):113-121
OBJECTIVES With large patient population and complement inhibitors naïve background, the characteristics patients with paroxysmal nocturnal hemoglobinuria (PNH) in China have not been well studied, especially for different subtypes. METHODS We retrospectively reviewed patients with complete data who visited Peking Union Medical College Hospital (PUMCH) from 2009 to 2019 and had been followed up for more than 2 years. RESULTS Five hundred and twelve patients were enrolled including 56.3% males and 43.7% females. The median age at disease onset was 33 (9∼80) years. Most were aged 21∼40 years (50.6%). 52.1%, 46.3% and 1.6% of the patients had classic PNH, bone marrow failure (BMF)/PNH and subclinical PNH, respectively. Symptoms of classic PNH were associated with hemolysis, whereas bleeding was more common in BMF/PNH patients. Classic PNH had higher survival rate, larger PNH clone size, higher lactate dehydrogenase (LDH) level and lower ferritin level than BMF/PNH. Although the rate of thrombosis was similar in the classic PNH and BMF/PNH (P = 0.66), those with BMF/PNH had higher chance of renal impairment (P < 0.05). Immunosuppressive agents was more common use in BMF/PNH (P < 0.05), but glucocorticoids, iron supplements and anticoagulants were more common used in classic PNH (P < 0.05) patients. Less evolution to myeloid malignancies was observed in classic PNH than in BMF/PNH (P = 0.02). The major causes of deaths were thrombosis (29.6%), hemorrhage (18.5%) and infections (18.5%). CONCLUSION Patients with classic PNH and BMF/PNH have different clinical profiles, and we described a more hemolytic features of PNH in China which might be improved with complement inhibitors.