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1.
Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.
Li, D, Wang, J, Tuo, Z, Yoo, KH, Yu, Q, Miyamoto, A, Zhang, C, Ye, X, Wei, W, Wu, R, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155503
Abstract
BACKGROUND Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN systematic review METHODS PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.
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2.
Advanced postoperative tissue antiadhesive membranes enabled with electrospun nanofibers.
Zhu, Y, Zhang, C, Liang, Y, Shi, J, Yu, Q, Liu, S, Yu, D, Liu, H
Biomaterials science. 2024;(7):1643-1661
Abstract
Tissue adhesion is one of the most common postoperative complications, which is frequently accompanied by inflammation, pain, and even dyskinesia, significantly reducing the quality of life of patients. Thus, to prevent the formation of tissue adhesions, various strategies have been explored. Among these methods, placing anti-adhesion membranes over the injured site to separate the wound from surrounding tissues is a simple and prominently favored method. Recently, electrospun nanofibers have been the most frequently investigated antiadhesive membranes due to their tunable porous structure and high porosities. They not only can act as an essential barrier and functional carrier system but also allow for high permeability and nutrient transport, showing great potential for preventing tissue adhesion. Herein, we provide a short review of the most recent applications of electrospun nanofibrous antiadhesive membranes in tendons, the abdominal cavity, dural sac, pericardium, and meninges. Firstly, each section highlights the most representative examples and they are sorted based on the latest progress of related research. Moreover, the design principles, preparation strategies, overall performances, and existing problems are highlighted and evaluated. Finally, the current challenges and several future ways to develop electrospun nanofibrous antiadhesive membranes are proposed. The systematic discussion and proposed directions can shed light on ideas and guide the reasonable design of electrospun nanofibrous membranes, contributing to the development of exceptional tissue anti-adhesive materials in the foreseeable future.
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3.
Anthocyanins-natural pigment of colored rice bran: Composition and biological activities.
Chen, T, Xie, L, Wang, G, Jiao, J, Zhao, J, Yu, Q, Chen, Y, Shen, M, Wen, H, Ou, X, et al
Food research international (Ottawa, Ont.). 2024;:113722
Abstract
Rice by-products are a potential source of various bioactive substances with great processing potential, which are receiving increasing attention. Among them, rice bran is a by-product of rice milling, with high nutritional value and health benefits. Colored rice bran contains a large amount of anthocyanins responsible for color and bioactivities. And anthocyanins are often added to foods as a natural pigment, serving to enhance both the visual appeal and nutritional value. Recent advances in the composition and bioactivities of four common colored rice bran anthocyanins (black, purple, red, and purple red rice) are reviewed in this paper. Rice bran anthocyanins have been confirmed to exhibit biological potential for human health, with their main biological activities being antioxidant, anti-atherosclerosis, anti-cancer, neuroprotective, retinoprotective, immunomodulatory, anti-aging and anti-obesity effects. The structure of anthocyanins determines their biological activities. The anthocyanins composition of rice bran with different colors varied greatly, while that of rice bran with the same color is also slightly different, which is attributed to the rice varieties, growing environment and cropping conditions. However, it remains necessary to conduct further clinical studies to support the health activities of anthocyanins. The present review provides information value for the further development and comprehensive utilization of rice bran anthocyanins.
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4.
Unbiased organism-agnostic and highly sensitive signal peptide predictor with deep protein language model.
Shen, J, Yu, Q, Chen, S, Tan, Q, Li, J, Li, Y
Nature computational science. 2024;(1):29-42
Abstract
Signal peptides (SPs) are essential to target and transfer transmembrane and secreted proteins to the correct positions. Many existing computational tools for predicting SPs disregard the extreme data imbalance problem and rely on additional group information of proteins. Here we introduce Unbiased Organism-agnostic Signal Peptide Network (USPNet), an SP classification and cleavage-site prediction deep learning method. Extensive experimental results show that USPNet substantially outperforms previous methods on classification performance by 10%. An SP-discovering pipeline with USPNet is designed to explore unprecedented SPs from metagenomic data. It reveals 347 SP candidates, with the lowest sequence identity between our candidates and the closest SP in the training dataset at only 13%. In addition, the template modeling scores between candidates and SPs in the training set are mostly above 0.8. The results showcase that USPNet has learnt the SP structure with raw amino acid sequences and the large protein language model, thereby enabling the discovery of unknown SPs.
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5.
Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.
Li, J, Zhang, L, Ge, T, Liu, J, Wang, C, Yu, Q
Drug design, development and therapy. 2024;:829-843
Abstract
Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.
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6.
Serum 25-Hydroxyvitamin D and Risk of Disability in Activities of Daily Living among the Oldest-Old: An Observational and Mendelian Randomization Study.
Li, X, Chen, C, Zhang, Y, Wang, J, Cui, X, Xu, L, Zhou, J, Deng, L, Zhang, M, Lv, Y, et al
The Journal of nutrition. 2024;(3):1004-1013
Abstract
BACKGROUND Vitamin D deficiency and disability are both prevalent among older adults. However, the association between them has rarely been investigated in the oldest-old subjects (aged ≥80 y), and the causality remains unclear. OBJECTIVE This study aimed to elucidate the causal effect of vitamin D on the incident risk of disability in activities of daily living (ADL) among Chinese oldest-old based on the 2012-2018 Chinese Healthy Ageing and Biomarkers Cohort Study. METHODS Serum 25-hydroxyvitamin D [25(OH)D] concentrations and ADL status at baseline and follow-up interviews were documented. Cox regression models were applied among 1427 oldest-old (mean age, 91.2 y) with normal baseline ADL status. One sample Mendelian randomization (MR) analyses were performed on a subset of 941 participants with qualified genetic data, using a 25(OH)D-associated genetic risk score as the genetic instrument. RESULTS During a median follow-up of 3.4 y, 231 participants developed disability in ADL. Serum 25(OH)D concentration was inversely associated with the risk of disability in ADL [per 10 nmol/L increase hazard ratio (HR) 0.85; 95% CI: 0.75, 0.96]. Consistent results from MR analyses showed that a 10 nmol/L increment in genetically predicted 25(OH)D concentration corresponded to a 20% reduced risk of ADL disability (HR 0.80; 95% CI: 0.68, 0.94). Nonlinear MR demonstrated a monotonic declining curve, with the HRs exhibiting a more pronounced reduction among individuals with 25(OH)D concentrations below 50 nmol/L. Subgroup analyses showed that the associations were more distinct among females and those with poorer health conditions. CONCLUSIONS Our study supports an inverse causal relationship between serum 25(OH)D concentration and the risk of disability in ADL among Chinese oldest-old. This protective effect was more distinct, especially for participants with vitamin D deficiency. Appropriate measures for improving vitamin D might help reduce the incidence of physical disability in this specific age group.
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7.
Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons.
He, Y, Dong, N, Wang, X, Lv, RJ, Yu, Q, Yue, HM
Sleep & breathing = Schlaf & Atmung. 2024
Abstract
Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA.
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8.
Association between type 1 diabetes and systemic lupus erythematosus: a Mendelian randomization study.
Liu, S, Si, S, Li, J, Zhao, Y, Yu, Q, Xue, F
Clinical rheumatology. 2024;(1):41-48
Abstract
OBJECTIVES Observational studies have shown that there is a bidirectional relationship between type 1 diabetes (T1D) and systemic lupus erythematosus (SLE); the causality of this association remains elusive and may be affected by confusion and reverse causality. There is also a lack of large-scale randomized controlled trials to verify. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and SLE. METHODS We aggregated data using publicly available genome-wide association studies (GWAS), all from European populations. Select independent (R2 < 0.001) and closely related to exposure (P < 5 × 10-8) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the primary method. We also used MR-Egger, the weighted median method, MR-Robust, MR-Lasso, and other methods leveraged as supplements. RESULTS T1D had a positive causal association with SLE (IVW, odds ratio [OR] = 1.358, 95% confidence interval [CI], 1.205 - 1.530; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.137, 95% CI, 1.033 - 1.251; P = 0.001). SLE had a positive causal association with T1D (IVW, OR = 1.108, 95% CI, 1.074 - 1.144; P < 0.001). The causal association was verified in an independent validation set (IVW, OR = 1.085, 95% CI, 1.046 - 1.127; P < 0.001). These results have also been verified by sensitivity analysis. CONCLUSION The MR analysis results indicated a causal association between T1D and SLE. Therefore, further research is needed to clarify the potential biological mechanism between T1D and SLE. Key Points • Observational studies have shown that there is a bidirectional relationship between T1D and SLE. • We evaluated causal effects between T1D and SLE by Mendelian randomization analyses. • The MR analysis results indicated a causal association between T1D and SLE.
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9.
A Single-dose, Two-Period Crossover Bioequivalence Study Comparing Two Liraglutide Formulations in Healthy Chinese Subjects.
Feng, S, Cai, L, Wang, X, Yu, Q, Cai, J, Hao, W, Chen, Z, Su, X, Du, C, Zou, Q, et al
Clinical pharmacology in drug development. 2023;(4):385-391
Abstract
Liraglutide, a glucagon-like peptide 1 receptor agonist, is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. The original liraglutide products are costly, which limits patient access to this therapeutic treatment. Herein, a biosimilar was developed that is highly similar to the reference drug in molecular structure and bioactivity, and is expected to have similar pharmacokinetic (PK) and safety profiles in clinical studies. This study aimed to primarily evaluate the bioequivalence of 2 liraglutide formulations and secondarily assess their safety in healthy Chinese subjects following a single-dose subcutaneous injection. Thirty-two healthy volunteers were recruited in this randomized, open-label, single-dose, 2-period crossover bioequivalence study (ChiCTR2100043348). The geometric mean ratios (GMRs) of the test drug to the reference drug (T/R) and corresponding 90% confidence intervals (CIs) for maximum concentration (Cmax ) and the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t ) were estimated using a mixed-effects model, and bioequivalence was determined to have been achieved if the 2-sided 90%CI fell within the predefined range of 80%-125%. PK parameters were comparable between T and R, with GMRs of T/R for Cmax and AUC0-t being 105.7% and 107.7%, respectively, the 90%CI of which met the acceptance criteria for bioequivalence. We also observed a similar and favorable safety profile in the T and R arms, with adverse events being predominantly mild in severity and of gastrointestinal origin. Our findings indicate that the test drug is safe and well tolerated, bioequivalent to the reference drug, and warrants further testing in a phase III clinical trial.
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10.
Applicable Strains, Processing Techniques and Health Benefits of Fermented Oat Beverages: A Review.
Yu, Q, Qian, J, Guo, Y, Qian, H, Yao, W, Cheng, Y
Foods (Basel, Switzerland). 2023;(8)
Abstract
Based on the high nutrients of oat and the demand of health-conscious consumers for value-added and functional foods, fermented oat beverages have great market prospects. This review summarizes the applicable strains, processing techniques and health benefits of fermented oat beverages. Firstly, the fermentation characteristics and conditions of the applicable strains are systematically described. Secondly, the advantages of pre-treatment processes such as enzymatic hydrolysis, germination, milling and drying are summarized. Furthermore, fermented oat beverages can increase the nutrient content and reduce the content of anti-nutritional factors, thereby reducing some risk factors related to many diseases such as diabetes, high cholesterol and high blood pressure. This paper discusses the current research status of fermented oat beverages, which has academic significance for researchers interested in the application potential of oat. Future studies on fermenting oat beverages can focus on the development of special compound fermentation agents and the richness of their taste.