Search

Abstract Immunity has shown potentials in informing drug development for cardiometabolic diseases, such as type 2 diabetes (T2D) and coronary artery disease (CAD). Here, we performed a transcriptome-wide Mendelian randomization (MR) study to estimate the putative causal effects of 11,021 gene expression profiles during CD4+ T cells activation on the development of T2D and CAD. Robust MR and colocalization evidence was observed for 162 genes altering T2D risk and 80 genes altering CAD risk, with 12% and 16% respectively demonstrating CD4+ T cell specificity. We observed temporal causal patterns during T cell activation in 69 gene-T2D pairs and 34 gene-CAD pairs. These genes were eight times more likely to show robust genetic evidence. We further identified 25 genes that were targets for drugs under clinical investigation, including LIPA and GCK. This study provides evidence to support immune-to-metabolic disease connections, and prioritises immune-mediated drug targets for cardiometabolic diseases.

Abstract Background An updated definition was developed to better evaluate cardiovascular health (CVH). We aimed to investigate whether optimal or improvement of six CVH metrics defined by new Life's Essential 8 (LE8) may counteract the risk of subclinical atherosclerosis among patients with hyperglycemia. Methods We conducted a prospective analysis of 5225 participants without prior cardiovascular diseases, of whom 4768 had complete data on CVH change. Subjects with CVH scores of 0–49, 50–79, and 80–100 points were categorized as having low, moderate, or high CVH, respectively. Subclinical atherosclerosis was evaluated by brachial‐ankle pulse wave velocity, pulse pressure and albuminuria, both separately and in combination. Results Of the 5225 participants, 1937 (37.1%) had normal glucose regulation, while 3288 (62.9%) had hyperglycemia. The multivariable‐adjusted odds ratio (OR) for composite subclinical atherosclerosis was 2.34 (95% confidence interval [CI], 1.88–2.91), 1.43 (95% CI, 1.21–1.70), and 0.74 (95% CI, 0.46–1.18), for participants with hyperglycemia who had low, moderate, or high overall CVH scores, respectively, compared with participants with normal glucose regulation. In addition, compared with those with stable CVH and normal glucose regulation, participants who exhibited greater improvements in overall CVH from 2010 to 2014 had a reduced risk of composite subclinical atherosclerosis with an OR of 0.72 (95% CI, 0.53–0.98) for those with normal glucose regulation, and 1.13 (95% CI, 0.87–1.48) for those with hyperglycemia. Conclusions The novel defined CVH using six metrics was inversely associated with subsequent risk of subclinical atherosclerosis. Both the status of CVH and its changes modified the relationship between hyperglycemia and subclinical atherosclerosis.

Abstract Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis, particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.

BackgroundCurrently, there are many surgical options for patellar dislocation. The purpose of this study is to perform a network meta-analysis of the randomized controlled trials (RCTs) and cohort studies to determine the better treatment.MethodWe searched the Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, clinicaltrials.gov and who.int/trialsearch. Clinical outcomes included Kujala score, Lysholm score, International Knee Documentation Committee (IKDC) score, redislocation or recurrent instability. We conducted pairwise meta-analysis and network meta-analysis respectively using the frequentist model to compare the clinical outcomes.ResultsThere were 10 RCTs and 2 cohort studies with a total of 774 patients included in our study. In network meta-analysis, double-bundle medial patellofemoral ligament reconstruction (DB-MPFLR) achieved good results on functional scores. According to the surface under the cumulative ranking (SUCRA), DB-MPFLR had the highest probabilities of their protective effects on outcomes of Kujala score (SUCRA 96.5 %), IKDC score (SUCRA 100.0%) and redislocation (SUCRA 67.8%). However, DB-MPFLR (SUCRA 84.6%) comes second to SB-MPFLR (SUCRA 90.4%) in Lyshlom score. It is (SUCRA 70%) also inferior to vastus medialis plasty (VM-plasty) (SUCRA 81.9%) in preventing Recurrent instability. The results of subgroup analysis were similar.ConclusionOur study demonstrated that MPFLR showed better functional scores than other surgical options.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), imposes a significant global burden with adverse clinical outcomes and escalating healthcare expenditures. Early identification of biomarkers can facilitate better screening, earlier diagnosis, and the prevention of diabetes. However, current clinical predictors often fail to detect abnormalities during the prediabetic state. Emerging studies have identified specific amino acids as potential biomarkers for predicting the onset and progression of diabetes. Understanding the underlying pathophysiological mechanisms can offer valuable insights into disease prevention and therapeutic interventions. This review provides a comprehensive summary of evidence supporting the use of amino acids and metabolites as clinical biomarkers for insulin resistance and diabetes. We discuss promising combinations of amino acids, including branched-chain amino acids, aromatic amino acids, glycine, asparagine and aspartate, in the prediction of T2DM. Furthermore, we delve into the mechanisms involving various signaling pathways and the metabolism underlying the role of amino acids in disease development. Finally, we highlight the potential of targeting predictive amino acids for preventive and therapeutic interventions, aiming to inspire further clinical investigations and mitigate the progression of T2DM, particularly in the prediabetic stage.

PurposeRotator cuff diseases, as a common cause of shoulder pain and disability, have seriously affected the patients' daily life. Rotator cuff repair techniques have been a hot topic in the arthroscopic therapy field. Our study was to use bibliometrics analysis to clarify the current status and research trends in the field of arthroscopic therapy of rotator cuff diseases.MethodsThe publications relating to arthroscopic therapy of rotator cuff diseases published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC) database. The R software and VOSviewer software were used for the cross-sectional bibliometric and scientometric analysis.ResultsA total of 4,567 publications about arthroscopic therapy of rotator cuff diseases published between 2002 and 2021 retrieved from the WoSCC database were analyzed in our study. The results showed that the United States made the largest contribution to this field. The most relevant institutions were Seoul National University, Rush University, and Hospital for Special Surgery. Stephen S Burkhart was the most relevant researcher in this field with the largest number of publications, as well as the highest H-index and G-index. The journal ARTHROSCOPY contributed the largest number of publications in the past 2 decades. Considering the H-index and G-index, ARTHROSCOPY was also the journal with the largest impact in this field.ConclusionsArthroscopic Therapy of Rotator Cuff Diseases Related research presented a rising trend in the past 2 decades. The United States can be regarded as the leader because of its huge contributions to this field. The journal ARTHROSCOPY published the largest number of publications in this field. It can be predicted that research about advanced arthroscopic techniques and postoperative pain management of patients with rotator cuff diseases will be the next research hotspots in the following years.

Background: Tetrandrine has been the focus of many studies in recent years. Currently, no bibliometric study in this field has been published. This study presents a bibliometric analysis of the articles on tetrandrine research from the WOS core database during the recent two decades.Methods: Documents were retrieved for further bibliometric analysis based on the search terms: [TI = (Tetrandrine OR Sinomeninea OR Hanfangchin A) AND PY = (2000–2021)]. We used Microsoft Excel to conduct the frequency analysis, VOSviewer for data visualization, and RStudio for citation metrics and analysis. The standard bibliometric indicators such as the temporal trends and geographical distribution of publications and citations, prolific authors and co-authorship, keywords citation burst, preferred journals, top-cited articles, and important institutions were applied in this study.Results: 490 documents were retrieved from WOS core database, the retrieved document type consists of 8 categories: 425 articles, 42 meeting abstracts, 8 reviews, 7 corrections, 3 editorial material, 2 proceedings paper, 1 letter, 1 retraction. Corrections and Retractions was excluded from this investigation, the left 482 document were included for furter bibliometric analysis.Conclusion: Based on our findings, there was a continuous growth of publications on tetrandrine research for 22 years since 2000. China was the largest contributor to tetrandrine research, followed by the United States. The most influential author was Cheng Y (Natl Taiwan Univ Hosp). Acta Pharmacol Sin remained the main publication related to tetrandrine research. Chinese Academy of Sciences, is expected to be a good collaborating center in tetrandrine research. The use of tetrandrine in cancer treatment, could be the promising research subject areas to follow.

Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells. This study aimed to clarify whether the sensory PGE2/EP4 pathway induces aberrant structural alteration of subchondral bone in osteoarthritis. Destabilization of the medial meniscus (DMM) using a mouse model was combined with three approaches: the treatment of celecoxib, capsaicin, and sensory nerve-specific prostaglandin E2 receptor 4 (EP4)-knockout mice. Cartilage degeneration, subchondral bone architecture, PGE2 levels, distribution of sensory nerves, the number of osteoprogenitors, and pain-related behavior in DMM mice were assessed. Serum and tissue PGE2 levels and subchondral bone architecture in a human sample were measured. Increased PGE2 is closely related to subchondral bone’s abnormal microstructure in humans and mice. Elevated PGE2 concentration in subchondral bone that is mainly derived from osteoblasts occurs in early-stage osteoarthritis, preceding articular cartilage degeneration in mice. The decreased PGE2 levels by the celecoxib or sensory denervation by capsaicin attenuate the aberrant alteration of subchondral bone architecture, joint degeneration, and pain. Selective EP4 receptor knockout of the sensory nerve attenuates the aberrant formation of subchondral bone and facilitates the prevention of cartilage degeneration in DMM mice. Excessive PGE2 in subchondral bone caused a pathological alteration to subchondral bone in osteoarthritis and maintaining the physiological level of PGE2 could potentially be used as an osteoarthritis treatment.

Osteoarthritis (OA), the most common degenerative joint disease, causes an enormous socioeconomic burden due to its disabling properties and high prevalence. Increasing evidence suggests that OA is a whole-joint disease involving cartilage degradation, synovitis, meniscal lesions, and subchondral bone remodeling. Endoplasmic reticulum (ER) stress is the accumulation of misfolded/unfolded proteins in the ER. Recent studies have found that ER stress is involved in the OA pathological changes by influencing the physiological function and survival of chondrocytes, fibroblast-like synoviocytes, synovial macrophages, meniscus cells, osteoblasts, osteoclasts, osteocytes, and bone marrow mesenchymal stem cells. Therefore, ER stress is an attractive and promising target for OA. However, although targeting ER stress has been proven to alleviate OA progression in vitro and in vivo, the treatments for OA remain in preclinical stage and require further investigation. [ABSTRACT FROM AUTHOR]