The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.

Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-ß, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.

Association between Cardiometabolic Index and Cognitive Function: A Cross-Sectional Study in a Diabetic-Based Population.

INTRODUCTION: Diabetes is a significant risk factor for cognitive impairment. Therefore, early identification of cognitive impairment in diabetic patients is particularly important. The aim of this study was to assess the relationship between Cardiometabolic index (CMI) and cognitive function in a diabetic population. METHODS: A cross-sectional study was conducted by collecting information from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multiple linear regression models were used to investigate the correlation between CMI and low cognitive function in a diabetic population. Threshold effects analysis and fitted smoothing curves were used to describe the nonlinear links. Interaction tests and subgroup analyses were also performed. RESULTS: A total of 1,050 people participated in this study, including 561 men and 489 women. In the fully corrected model, CMI was positively associated with low cognitive performance as assessed by CERAD Word List Learning Test (CERAD W-L), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST) (OR = 1.37 [1.14, 1.72], p = 7.4 × 10-3), (OR = 1.21 [1.04, 1.51], p = 1.26 × 10-2), and (OR = 1.27 [1.08, 1.63], p = 2.53 × 10-2). Our study found that diabetic patients with higher CMI were at greater risk of developing low cognitive function. The effect of the subgroups on the positive association of CMI with cognitive impairment was not significant. A non-linear association between low cognitive performance and CMI was determined by CERAD W-L, AFT, and DSST (log-likelihood ratio <5 × 10-2). In addition, our also study found that CMI was a better predictor of cognitive impairment in diabetes than weight-adjusted waist index (WWI). CONCLUSION: Increased CMI is associated with an increased risk of cognitive impairment in people with diabetes. CMI can be used as a new anthropometric measure for predicting cognitive impairment in diabetes, with stronger predictive power than WWI.

Association between cardiometabolic index and asthma in adults: evidence from NHANES 2005-2018.

OBJECTIVES: Cardiometabolic Index (CMI) is a surrogate marker for metabolic disorders. It is associated with various chronic diseases. This study aims to investigate the relationship between CMI and asthma. METHODS: Data from seven consecutive National Health and Nutrition Examination Survey cycles between 2005 and 2018 were used. The study included adults with self-reported asthma diagnoses and complete information for CMI calculation. The formula for CMI is CMI = [WC (cm)/height (cm)] × [TG (mg/dL)/HDL-C (mg/dL)]. A multivariate logistic regression model was employed to examine the linear relationship between CMI and asthma. Subgroup analyses were conducted to explore potential influencing factors. Additionally, smooth curve fitting and threshold effect analysis were used to describe the non-linear relationship. RESULTS: A higher CMI was possibly associated with an increased prevalence of asthma. After adjusting for various covariates including marital status, Poverty Income Ratio, Body Mass Index, hypertension, diabetes, smoking, alcohol consumption, heart attack, and stroke, the results remained significant (OR = 1.03; 95%CI, 1.00-1.05, p = 0.0178, R2 = 0.52). Participants with the highest CMI had a 38% increased risk of asthma prevalence compared to those with the lowest CMI (OR = 1.38; 95%CI, 1.19-1.60, p < 0.0001). CONCLUSION: The findings reveal that elevated CMI levels correlate with an increased risk of asthma, highlighting CMI's potential as a predictive marker for asthma, particularly in populations with a CMI below 1.97. These results suggest that interventions aimed at improving metabolic health may prove effective in managing or preventing asthma.

Ferroptosis: Latest evidence and perspectives on plant-derived natural active compounds mitigating doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first-line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin-induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX-induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC. This review explores the mechanisms of ferroptosis in doxorubicin-induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.

Modulation of atherosclerosis-related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives.

Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-E2-related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator-activated receptor (PPAR), nucleotide oligo-structural domain-like receptor thermoprotein structural domain-associated protein 3 (NLRP3), silencing information regulator 2-associated enzyme 1 (Sirt1), nuclear transcription factor-κB (NF-κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor-ß (TGF-ß), and Janus kinase-signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high-intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.

Efficacy of five different traditional Chinese medicine injections in acute upper respiratory tract infection in children: a network meta-analysis and systematic review.

Background: Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional Chinese medicine (TCM) injections are widely used for treating AURI in clinical practice, but their efficacy is unclear because of the lack of clear evidence. In this study, a network meta-analysis (NMA) was used to evaluate the efficacy and safety of TCM injections in the treatment of AURI and to provide a reference for clinical treatment. Methods: Eight databases were searched, namely, PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), the Wanfang database, and the Chinese Scientific Journal database (VIP). The search time period was from 1 January 2013 to 1 November 2023. Randomized controlled trials of herbal injections for treating AURI were searched. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of these studies. Review Manager 5.4 and Stata 15.0 were used for the NMA. Results: A total of 81 papers involving 11,736 patients were included. These involved five different TCM injections, namely, Xiyanping injection (XYPI), Qingkailing injection (QKLI), Reduning injection (RDNI), Yanhuning injection (YHNI), and Tanreqing injection (TRQI). QKLI was most effective in alleviating symptoms of fever and improving overall clinical effectiveness. TRQI was most effective in relieving cough symptoms. YHNI was most effective in alleviating sore throat, runny nose, and nasal congestion. The overall incidence of adverse effects of these herbal injections in the treatment of AURI was lower, and their safety profiles were better. Conclusions: The herbal injections combined with ribavirin improved clinical outcomes, and were superior to ribavirin injection alone in alleviating clinical symptoms such as fever, cough, sore throat, runny nose, and nasal congestion, and have favorable safety profiles. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023484099, CRD42023484099.

Effects of modified Danggui Sini Decoction as adjuvant therapy for angina pectoris in coronary heart disease: a systematic review and meta-analysis based on randomised controlled trials.

Introduction: This systematic review evaluates the efficacy of the Chinese herbal formula modified Danggui Sini Decoction as an adjunctive treatment for angina pectoris in patients with coronary heart disease. Methods: We conducted a comprehensive search for randomized controlled trials that investigated the effects of modified Danggui Sini Decoction in combination with conventional Western medication on angina pectoris in coronary artery disease, published up to July 2023 across eight databases, including China Knowledge International Literature screening and data extraction were performed by two researchers following predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Cochrane Handbook version 5.1, and meta-analysis was executed via RevMan 5.4 software. Results: Thirteen studies encompassing 1,232 participants were incorporated. The meta-analysis revealed that combining modified Danggui Sini Decoction with conventional Western medication significantly enhanced overall clinical efficacy, reduced the duration of angina attacks, decreased the Chinese medicine syndrome score, improved inflammatory markers and cardiac function, lowered serum NT-proBNP levels, and elevated the Seattle Angina Questionnaire scores compared to the control group. Conclusion: Modified Danggui Sini Decoction, when used alongside conventional Western medications, shows promise in treating coronary artery disease patients with angina pectoris and may serve as a beneficial adjunctive therapy in clinical settings. Nonetheless, due to the limited quantity and quality of the included studies, further high-caliber research is essential to substantiate these findings. Systematic Review Registration: https://inplasy.com/? s=202390078, identifier INPLASY 202390078.

Therapeutic Role of Chinese Medicine Targeting Nrf2/HO-1 Signaling Pathway in Myocardial Ischemia/Reperfusion Injury.

Acute myocardial infarction (AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury (MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.

A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.

Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast-mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age-related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age-induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

The Dynamic Changes of Brassica napus Seed Microbiota across the Entire Seed Life in the Field.

The seed microbiota is an important component given by nature to plants, protecting seeds from damage by other organisms and abiotic stress. However, little is known about the dynamic changes and potential functions of the seed microbiota during seed development. In this study, we investigated the composition and potential functions of the seed microbiota of rapeseed (Brassica napus). A total of 2496 amplicon sequence variants (ASVs) belonging to 504 genera in 25 phyla were identified, and the seed microbiota of all sampling stages were divided into three groups. The microbiota of flower buds, young pods, and seeds at 20 days after flowering (daf) formed the first group; that of seeds at 30 daf, 40 daf and 50 daf formed the second group; that of mature seeds and parental seeds were clustered into the third group. The functions of seed microbiota were identified by using PICRUSt2, and it was found that the substance metabolism of seed microbiota was correlated with those of the seeds. Finally, sixty-one core ASVs, including several potential human pathogens, were identified, and a member of the seed core microbiota, Sphingomonas endophytica, was isolated from seeds and found to promote seedling growth and enhance resistance against Sclerotinia sclerotiorum, a major pathogen in rapeseed. Our findings provide a novel perspective for understanding the composition and functions of microbiota during seed development and may enhance the efficiency of mining beneficial seed microbes.