-
1.
Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.
Wu, Y, Qian, Q, Liu, Q, Wang, R, Pu, X, Li, Y, Zhang, H, You, Z, Miao, Q, Xiao, X, et al
Clinical reviews in allergy & immunology. 2024
Abstract
Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.
-
2.
Lessons learned from regulatory submissions involving endogenous therapeutic analyte bioanalysis.
Yu, C, Jiang, W, Matta, M, Wang, R, Haidar, S, Seo, H
Bioanalysis. 2024;(3):171-184
Abstract
Endogenous therapeutic analytes include hormones, neurotransmitters, vitamins, fatty acids and inorganic elements that are naturally present in the body because either the body produces them or they are present in the normal diet. The accurate measurement of endogenous therapeutic analytes poses a challenge when the administered exogenous therapeutic analyte and its endogenous counterpart cannot be distinguished. In this article, real case examples with endogenous therapeutic analyte bioanalysis during drug development in support of regulatory submissions are collected and presented. The article highlights common challenges encountered and lessons learned related to bioanalysis of endogenous therapeutic analytes and provides practical tips and strategies to consider from a regulatory perspective.
-
3.
Dissecting the roles of calcium cycling and its coupling with voltage in the genesis of early afterdepolarizations in cardiac myocyte models.
Wang, R, Qu, Z, Huang, X
PLoS computational biology. 2024;(2):e1011930
Abstract
Early afterdepolarizations (EADs) are abnormal depolarizations during the plateau phase of the action potential, which are known to be associated with lethal arrhythmias in the heart. There are two major hypotheses for EAD genesis based on experimental observations, i.e., the voltage (Vm)-driven and intracellular calcium (Ca)-driven mechanisms. In ventricular myocytes, Ca and Vm are bidirectionally coupled, which can affect each other's dynamics and result in new dynamics, however, the roles of Ca cycling and its coupling with Vm in the genesis of EADs have not been well understood. In this study, we use an action potential model that is capable of independent Vm and Ca oscillations to investigate the roles of Vm and Ca coupling in EAD genesis. Four different mechanisms of EADs are identified, which are either driven by Vm oscillations or Ca oscillations alone, or oscillations caused by their interactions. We also use 5 other ventricular action potential models to assess these EAD mechanisms and show that EADs in these models are mainly Vm-driven. These mechanistic insights from our simulations provide a theoretical base for understanding experimentally observed EADs and EAD-related arrhythmogenesis.
-
4.
Quality reporting of randomized controlled trials on SGLT2 inhibitors for heart failure: a comprehensive assessment.
Yang, Y, Yang, S, Han, Y, Zou, G, Wang, R, Liu, L
Scientific reports. 2024;(1):6819
Abstract
Randomised controlled trials (RCTs) provide clinicians with the best evidence of the effectiveness of an intervention, and complete and transparent trial reports help to critically assess and use trial results. The objective of our study was to assess the quality of reporting in RCTs of sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for heart failure (HF) and identify factors associated with improved reporting quality. Two researchers conducted a comprehensive search in four databases (PubMed, Web of Science, EMBASE, and Cochrane). The quality of each report was assessed using a 25-point Overall Quality Score (OQS) based on the guidelines provided in the 2010 Consolidated Standards for Reporting of Trials (CONSORT) statement. We included a total of 58 relevant RCTs. The median OQS in the 2010 CONSORT statement was 15 (range 7.5-24). The missing items were primarily found in the 'Methods' and 'Results' sections of the 2010 CONSORT statement. Multivariate regression modeling revealed that a more recent publication year, high impact factor, and large sample size were significant predictors of OQS improvement. The findings suggest that the overall quality of reported RCTs of SGLT2 inhibitors in HF is unsatisfactory, which reduces their potential usefulness.
-
5.
Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis.
Min, L, Ablitip, A, Wang, R, Luciana, T, Wei, M, Ma, X
Nutrients. 2024;(7)
Abstract
BACKGROUND The equilibrium between gut microbiota (GM) and the host plays a pivotal role in maintaining overall health, influencing various physiological and metabolic functions. Emerging research suggests that exercise modulates the abundance and functionality of gut bacteria, yet the comprehensive effects on GM diversity remain to be synthesized. OBJECTIVES AND DESIGN The study aims to quantitatively examine the effect of exercise on the diversity of gut microbiota of adults using a systemic review and meta-analysis approach. METHODS PubMed, Ebsco, Embase, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, and Wanfang Data were searched from their inception to September 2023. Exercise intervention studies with a control group that describe and compare the composition of GM in adults, using 16S rRNA gene sequencing, were included in this meta-analysis. RESULTS A total of 25 studies were included in this meta-analysis with a total of 1044 participants. Based on a fixed-effects model [Chi2 = 29.40, df = 20 (p = 0.08); I2 = 32%], the pooled analysis showed that compared with the control group, exercise intervention can significantly increase the alpha diversity of adult GM, using the Shannon index as an example [WMD = 0.05, 95% CI (0.00, 0.09); Z = 1.99 (p = 0.05)]. In addition, exercise interventions were found to significantly alter GM, notably decreasing Bacteroidetes and increasing Firmicutes, indicating a shift in the Firmicutes/Bacteroidetes ratio. The subgroup analysis indicates that females and older adults appear to exhibit more significant changes in the Shannon Index and observed OTUs. CONCLUSIONS Exercise may be a promising way to improve GM in adults. In particular, the Shannon index was significantly increased after exercise. Distinct responses in GM diversity to exercise interventions based on gender and age implicated that more research was needed.
-
6.
The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.
Song, Z, Wu, C, Wang, R, Gillis, A, Fazendin, J, Lindeman, B, Chen, H
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2024
Abstract
OBJECTIVE The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.
-
7.
Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives.
Wang, R, Wang, C, Lu, L, Yuan, F, He, F
Pharmacological research. 2024;:107032
-
-
Free full text
-
Abstract
Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy.
-
8.
Emerging role of ferroptosis in diabetic retinopathy: a review.
Wang, R, Rao, S, Zhong, Z, Xiao, K, Chen, X, Sun, X
Journal of drug targeting. 2024;(4):393-403
Abstract
BACKGROUND Diabetic retinopathy (DR) is a significant complication of diabetes and the primary cause of blindness among working age adults globally. The development of DR is accompanied by oxidative stress, characterised by an overproduction of reactive oxygen species (ROS) and a compromised antioxidant system. Clinical interventions aimed at mitigating oxidative stress through ROS scavenging or elimination are currently available. Nevertheless, these treatments merely provide limited management over the advanced stage of the illness. Ferroptosis is a distinctive form of cell death induced by oxidative stress, which is characterised by irondependent phospholipid peroxidation. PURPOSE This review aims to synthesise recent experimental evidence to examine the involvement of ferroptosis in the pathological processes of DR, as well as to explicate the regulatory pathways governing oxidative stress and ferroptosis in retina. METHODS We systematically reviewed literature available up to 2023. RESULTS This review included 12 studies investigating the involvement of ferroptosis in DR.
-
9.
The effect of vitamin D supplementation on primary depression: A meta-analysis.
Wang, R, Xu, F, Xia, X, Xiong, A, Dai, D, Ling, Y, Sun, R, Qiu, L, Ding, Y, Xie, Z
Journal of affective disorders. 2024;:653-661
Abstract
BACKGROUND Previous meta-analyses reported inconsistent results on the effect of vitamin D on depression because of different baseline concentrations of 25-hydroxyvitamin D [25(OH)D], highlighting the need for a more accurate subgroup analysis of previously published findings. The goal of the present study was to evaluate the effect of vitamin D supplementation on depression in adults. METHODS A systematic search in numerous databases including PubMed, Embase, and Web of Science was performed. Randomized-controlled trials comparing the effect of vitamin D on depression in adults were selected. RESULTS Eighteen studies met the inclusion criteria in the retrieved citations. The meta-analysis showed that vitamin D supplementation had a significant effect on overall reduction in depression symptom scores (SMD = -0.15, 95 % CI [-0.26, -0.04]). Sub-group analysis showed that vitamin D supplementation significantly reduced depressive symptom scores in patients with serum 25(OH)D levels higher than 50 nmol/L (SMD = -0.38, 95 % CI [-0.68, -0.08]). CONCLUSIONS Vitamin D supplementation has a benefit on improving depressive symptoms in adults with primary depression and 25(OH)D levels higher than 50 nmol/L but has no effect on improving depressive symptoms in adults with primary depression and 25(OH)D levels lower than 50 nmol/L. Relatively high levels of 25(OH)D maybe required for alleviating depression. LIMITATIONS The randomized studies included in this study were designed and completed at different times and countries, the variability in duration and dose of vitamin D supplementation may have introduced significant heterogeneity and have militated against observation of the effects of vitamin D supplementation on depression.
-
10.
Recent advances in photo-crosslinkable methacrylated silk (Sil-MA)-based scaffolds for regenerative medicine: A review.
He, X, Wang, R, Zhou, F, Liu, H
International journal of biological macromolecules. 2024;(Pt 1):128031
Abstract
Silks fibroin can be chemically modified through amino acid side chains to obtain methacrylated silk (Sil-MA). Sil-MA could be processed into a variety of scaffold forms and combine synergistically with other biomaterials to form composites vehicle. The advent of Sil-MA material has enabled impressive progress in the development of various scaffolds based on Sil-MA type to imitate the structural and functional characteristics of natural tissues. This review highlights the reasonable design and bio-fabrication strategies of diverse Sil-MA-based tissue constructs for regenerative medicine. First, we elucidate modification methodology and characteristics of Sil-MA. Next, we describe characteristics of Sil-MA hydrogels, and focus on the design approaches and formation of different types of Sil-MA-based hydrogels. Thereafter, we present an overview of the recent advances in the application of Sil-MA based scaffolds for regenerative medicine, including detailed strategies for the engineering methods and materials used. Finally, we summarize the current research progress and future directions of Sil-MA in regenerative medicine. This review not only delineates the representative design strategies and their application in regenerative medicine, but also provides new direction in the fabrication of biomaterial constructs for the clinical translation in order to stimulate the future development of implants.