The mechanism and promising therapeutic strategy of diabetic cardiomyopathy dysfunctions: Focus on pyroptosis.

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

Evaluation of Quantitative and Selective Sensory Fiber Dysfunction in Patients with Cirrhosis.

BACKGROUND: Chronic liver disease has been reported to be associated with peripheral neuropathy. However, which sensory fibers are affected remains unknown. The objective of this study was to examine the function of sensory nerve fibers in patients with cirrhosis using the current perception threshold (CPT) test, as well as the correlation between blood biochemical indicators related to cirrhosis and CPT values. METHODS: We recruited 44 patients with liver cirrhosis and 37 healthy controls of the same age and gender. The Neurometer® system for the CPT test was used to stimulate the median nerve on the right index finger, as well as the deep and superficial peroneal nerves on the right hallux, using three distinct parameters (2000 Hz, 250 Hz, and 5 Hz). Comparative analysis was performed on the CPT values of the sensory nerves. Additionally, the correlation between CPT values and biochemical blood indicators in the study participants was analyzed. RESULTS: Under 2000 Hz electrical stimulation, there was a significant difference between the cirrhosis and healthy control groups in the median nerve as well as the deep and superficial peroneal nerves (p < 0.05). In addition, the median nerve CPT value of the cirrhosis group was significantly higher than that of the control group at an electrical stimulation frequency of 250 Hz (p = 0.005). There was no correlation between CPT values and blood biochemical indicators. CONCLUSION: According to the results, the sensory peripheral neuropathy in liver cirrhosis is mainly manifested as Aß fiber neuropathy.

Nuclear magnetic resonance-based metabolomic study of rat serum after anterior cruciate ligament injury.

Anterior cruciate ligament (ACL) injury, a common sports injury, is associated with a high risk of subsequent osteoarthritis (OA), which can cause serious pain and disability. Understanding the detailed mechanism underlying the predisposition of knee with ACL injury to secondary OA at an early stage is key to preventing future degradation and progression to a clinically significant disease. A total of 56 male Sprague Dawley rats (age, 8 weeks; weight, 180-220 g) were randomly divided into three experimental groups: control, ACL transection (ACLT; where surgical procedure was performed with ACLT), and sham (where surgical procedure was performed without ACLT). The ACLT and sham groups were further divided into three subgroups based on when the rats were sacrificed: 4, 8, and 12 weeks after the surgical procedure. The control group and the aforementioned subgroups contained 8 rats each. We used nuclear magnetic resonance (NMR)-based metabolomic analysis to analyze rat serum samples for the metabolic characteristics and the underlying mechanisms. In total, 28 metabolites were identified in the NMR spectra of the rat sera. At 4 and 8 weeks postoperatively, the sham group demonstrated metabolic profiles different from those of the ACLT group. However, this difference was not observed 12 weeks postoperatively. In total, five metabolites (acetate, succinate, sn-glycero-3-phosphocholine, glucose, and phenylalanine) and five metabolic pathways (phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; pyruvate metabolism; starch and sucrose metabolism; and histidine metabolism) demonstrated significant differences between the ACLT and sham groups. ACL injury was noted to considerably affect biochemical homeostasis and metabolism; however, these metabolic changes persisted briefly. Moreover, glucose was a characteristic metabolite, and several energy-related metabolic pathways were significantly disturbed. Therefore, an ACL injury may lead to considerable impairments in energy metabolism. Abnormal glucose levels facilitate chondrocyte function impairment and thereby lead to OA progression. Furthermore, lactate may aid in identifying metabolic changes specific to knee trauma not related to an ACL injury. Overall, the metabolic changes in rat serum after an ACL injury were closely related to disturbances in energy metabolism and amino acid metabolism. The current results may aid in understanding the pathogenesis of posttraumatic osteoarthritis.

Investigation into the Effectiveness of Combining Transcranial Direct Current Stimulation and Transcutaneous Electrical Nerve Stimulation as Treatment Options for Poststroke Shoulder Pain by Utilizing Functional Near-Infrared Spectroscopy.

Objective: The aim of this study is to explore the therapeutic effects of transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) on post stroke shoulder pain (PSSP). Methods: We enrolled 13 individuals in this study who underwent three different treatments in a random sequence: active tDCS+active TENS, active tDCS+sham TENS, and sham tDCS+active TENS. Each treatment was administered once, with a 3-day washout period between interventions. A blinded rater assessed the visual analog scale (VAS) scores, fNIRS readings, and sensory and pain tolerance thresholds of the participants before and after the stimulation. Results: All three treatment methods can significantly alleviate PSSP (p<0.05). Compared with using tDCS alone, tDCS+TENS can significantly improve pain, with a statistically significant difference (p<0.05). In the 2KHz PTT task, the three treatment methods showed significant differences (p<0.05) in the mean oxygenated hemoglobin (HbO) levels in the false premotor cortex (PMC)/auxiliary motor area (SMA) before and after intervention. Conclusion: The combination of tDCS+TENS can increase the pain-relieving impact on PSSP when compared to using tDCS alone. TENS may contribute an additional effect on the inhibitory systems influenced by tDCS that help reduce pain. Clinical Registration Number: Registration website: https://www.chictr.org.cn. Registration date: 2022-02-25. Registration number: ChiCTR2200056970.

LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression.

We aimed to investigate potential roles of LRRC75A-AS1 delivered by M2 macrophage exosomes in inducing cervical cancer progression. We demonstrated LRRC75A-AS1 was highly expressed in exosomes from M2 macrophages which could be absorbed by Hela cells. M2 macrophage-derived exosomes promoted Hela cell proliferation, migration, invasion, and EMT process by delivering LRRC75A-AS1. LRRC75A-AS1 directly targeted and suppressed miR-429 in Hela cells. The regulation of cell functions by exosomes from LRRC75A-AS1-overexpressing M2 macrophages was abrogated by miR-429 mimics. miR-429 directly targeted and repressed SIX1 expression. SIX1 overexpression alleviated the modulation of cellular functions and STAT3/MMP-9 signaling by miR-429 mimics. Also, miR-429 overexpression or SIX1 silence repressed tumor formation and metastasis in nude mice, which was mitigated by exosomes from LRRC75A-AS1-overexpressing M2 macrophages. In conclusion, LRRC75A-AS1 delivered by M2 macrophage exosomes repressed miR-429 to elevate SIX1 expression and promote cervical cancer progression through activating the STAT3/MMP-9 axis.

A case with type â ¡ vesicouterine fistula.

Here, we report a 41-year-old female with type II VUF after hysteromyomectomy.We report the diagnosis of VUF by imaging method, and provide a feasible treatment for this complication after pelvic surgery.

Treadmill running induces remodeling of the infrapatellar fat pad in an intensity-dependent manner.

OBJECTIVE: To investigate the response of the infrapatellar fat pad (IFP) to running at different intensities and further explore the underlying mechanisms of these responses under different running-induced loadings. METHODS: Animals were randomly assigned into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. The rats in the LIR, MIR, and HIR groups were subjected to an 8-week treadmill running protocol. In each group, the IFP was examined at the baseline and at the 8th week to perform histomorphology, immunohistochemistry, and mRNA expression analyses. RESULTS: Compared with LIR and MIR, HIR for 8 weeks led to a substantial increase in the surface cellularity (1.67 ± 1.15), fibrosis (1.29 ± 0.36), and vascularity (33.31 ± 8.43) of the IFP but did not increase IFP inflammation or M1 macrophage polarization. Low-to-medium-intensity running resulted in unchanged or decreased fibrosis, vascularity, and surface cellularity in the IFP compared to those of the SED group. Furthermore, serum leptin and visfatin levels were significantly lower in the LIR and MIR groups than in the SED group or the HIR group (P < 0.05). CONCLUSION: The effect of running on IFP remodeling was intensity dependent. In contrast to LIR and MIR, HIR increased the fibrosis and vascularity of the IFP. HIR-induced IFP fibrosis was probably due to mechanical stress, rather than pathological proinflammatory M1/M2 polarization.

Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA). METHOD: We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76-5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26-0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20-0.58; I2 = 49%; P < 0.0001). Changes in the cartilage surface morphology of the medial tibio-femoral joint (MD = -0.30, 95% CI -0.44 to -0.16; I2 = 0%; P < 0.0001) and patello-femoral joint (MD = -0.22; 95% CI -0.37 to -0.07; I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52-2.14; I2 = 48%; P = 0.89). CONCLUSION: The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.

COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials.

Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy.

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2 (ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPK kinases, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

A review of applications of metabolomics in osteoarthritis.

Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals.

Infrapatellar Fat Pad and Knee Osteoarthritis.

Osteoarthritis is the most prevalent arthritis typically characterized by degradation of cartilage. However, its pathogenesis is not fully understood. Currently, osteoarthritis is best considered a disease of the whole "joint organ". Infrapatellar fat pad (IFP), an adipose tissue near synovium, is now attaching importance to researchers for its inflammatory phenotype. In this narrative review, a large body of evidence has been gathered for the involvement of IFP in the development of knee osteoarthritis. Additionally, the underlying mechanisms of how IFP can be involved in this process have been proposed. However, further investigations are needed to better understand its precise role in this process and its underlying mechanism, and beyond that, to develop new strategies to slow down the degenerative process and explore an effective and timely diagnosis of the disease.

Post-traumatic osteoarthritis following ACL injury.

Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear "start point" for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus.

AIM: To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. RESULTS: Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95%CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95%CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95%CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%CI, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. CONCLUSION: Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR.