Synergistically Anti-Multiple Myeloma Effects: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib

Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. Bortezomib(BTZ), a first-generation protease inhibitor, has increased overall survival, progression-free survival, and remission rates in patients with MM since its clinical approval in 2003. However, the use of BTZ is challenged by the malignant features of MM and drug resistance. Polyphenols, classified into flavonoid and non-flavonoid polyphenols, have potential health-promoting activities, including anti-cancer. Previous preclinical studies have demonstrated the anti-MM potential of some dietary polyphenols. Therefore, these dietary polyphenols have the potential to be alternative therapies in anti-MM treatment regimens. This systematic review examines the synergistic effects of flavonoids and non-flavonoid polyphenols on the anti-MM impacts of BTZ. Preclinical studies on flavonoids and non-flavonoid polyphenols-BTZ synergism in MM were collected from PubMed, Web of Science, and Embase published between 2008 and 2020. 19 valid preclinical studies (Published from 2008 to 2020) were included in this systematic review. These studies demonstrated that eight flavonoids (icariin, icariside II, (-)-epigallocatechin-3-gallate, scutellarein, wogonin, morin, formononetin, daidzin), one plant extract rich in flavonoids (Punica granatum juice) and four non-flavonoid polyphenols (silibinin, resveratrol, curcumin, caffeic acid) synergistically enhanced the anti-MM effect of BTZ. These synergistic effects are mediated through the regulation of cellular signaling pathways associated with proliferation, apoptosis, and drug resistance. Given the above, flavonoids and non-flavonoid polyphenols can benefit MM patients by overcoming the challenges faced in BTZ treatment. Despite the positive nature of this preclinical evidence, some additional investigations are still needed before proceeding with clinical studies. For this purpose, we conclude by providing some suggestions for future research directions

Insight into telomere regulation: road to discovery and intervention in plasma drug-protein targets

Background Telomere length is a critical metric linked to aging, health, and disease. Currently, the exploration of target proteins related to telomere length is usually limited to the context of aging and specific diseases, which limits the discovery of more relevant drug targets. This study integrated large-scale plasma cis-pQTLs data and telomere length GWAS datasets. We used Mendelian randomization(MR) to identify drug target proteins for telomere length, providing essential clues for future precision therapy and targeted drug development. Methods Using plasma cis-pQTLs data from a previous GWAS study (3,606 Pqtls associated with 2,656 proteins) and a GWAS dataset of telomere length (sample size: 472,174; GWAS ID: ieu-b-4879) from UK Biobank, using MR, external validation, and reverse causality testing, we identified essential drug target proteins for telomere length. We also performed co-localization, Phenome-wide association studies and enrichment analysis, protein-protein interaction network construction, search for existing intervening drugs, and potential drug/compound prediction for these critical targets to strengthen and expand our findings. Results After Bonferron correction (p  0.8). Conclusion Genetically determined plasma RPN1, GDI2, NT5C, and TYRO3 have significant causal effects on telomere length and can potentially be drug targets. Further exploration of the role and mechanism of these proteins/genes in regulating telomere length is needed

Potential effects of bisphenol A on diabetes mellitus and its chronic complications: A narrative review

Diabetes mellitus (DM) is a metabolic disease caused by multiple factors such as genetics, environment, and lifestyle. Bisphenol A (BPA), as one of the most common endocrine-disrupting chemicals (EDCs), has been strongly implicated in the development of type 2 diabetes mellitus (T2DM). BPA exposure is associated with target organ damage in DM and may exacerbate the progression of some chronic complications of DM. This paper reviews relevant epidemiological, in vivo, and in vitro studies to better understand BPA's potential risk associations and pathological mechanisms in several chronic diabetic complications

Three-dimensional meteorological drought characteristics and associated risk in China

Drought as a hazardous natural disaster has been widely studied based on various drought indices. However, the characteristics of droughts have not been robustly explored considering its dual nature in space and time across China in the past few decades. Here, we characterized meteorological drought events from a three-dimensional perspective for the 1961–2018 period in the mainland of China, and attributed the variation of drought intensity to its influencing factors. We further assessed associated drought risk with socioeconomic data for the 2002–2018 period. We found that drought events with high intensity, large area, and long duration are mainly distributed in western and northern China, especially in Inner Mongolia, Xinjiang, Tibet, and Qinghai. The drought intensity and affected area anomalies present a six-phase pattern of ‘negative-positive-negative-positive-negative-positive’ during 1961–2018. The intensity of drought events showed a decreasing trend but the affected area and duration showed an increasing trend in 2009–2018. Over the decades, the centers of high drought intensity and long duration tend to move eastward and northeastward, respectively. The PET variations contributes larger than precipitation variations to drought intensity variations in the arid regions while being opposite in the humid southern regions. Drought risk assessment further indicates that high drought risk areas are concentrated in northern China, including Inner Mongolia, Xinjiang, Gansu, Sichuan, Hebei, and Heilongjiang. Increasing trends in drought risk for the 2002–2018 period are detected in Inner Mongolia, Xinjiang, Sichuan, Henan, Gansu, Hunan, Shanxi, Qinghai. Our findings provide scientific guidance for policymakers to develop adaptive disaster prevention measures

The therapeutic potential of quercetin for cigarette smoking–induced chronic obstructive pulmonary disease: a narrative review

Quercetin is a flavonoid with antioxidant and anti-inflammatory properties. Quercetin has potentially beneficial therapeutic effects for several diseases, including cigarette smoking–induced chronic obstructive pulmonary disease (CS-COPD). Many studies have shown that quercetin’s antioxidant and anti-inflammatory properties have positive therapeutic potential for CS-COPD. In addition, quercetin’s immunomodulatory, anti-cellular senescence, mitochondrial autophagy–modulating, and gut microbiota–modulating effects may also have therapeutic value for CS-COPD. However, there appears to be no review of the possible mechanisms of quercetin for treating CS-COPD. Moreover, the combination of quercetin with common therapeutic drugs for CS-COPD needs further refinement. Therefore, in this article, after introducing the definition and metabolism of quercetin, and its safety, we comprehensively presented the pathogenesis of CS-COPD related to oxidative stress, inflammation, immunity, cellular senescence, mitochondrial autophagy, and gut microbiota. We then reviewed quercetin’s anti-CS-COPD effects, performed by influencing these mechanisms. Finally, we explored the possibility of using quercetin with commonly used drugs for treating CS-COPD, providing a basis for future screening of excellent drug combinations for treating CS-COPD. This review has provided meaningful information on quercetin’s mechanisms and clinical use in treating CS-COPD

Aryl Hydrocarbon Receptor: A New Player of Pathogenesis and Therapy in Cardiovascular Diseases

The aryl hydrocarbon receptor (AhR) is a DNA binding protein that acts as a nuclear receptor mediating xenobiotic metabolism and environmental responses. Owing to the evolutionary conservation of this gene and its widespread expression in the immune and circulatory systems, AhR has for many years been almost exclusively studied by the pharmacological/toxicological field for its role in contaminant toxicity. More recently, the functions of AhR in environmental adaption have been examined in the context of the occurrence, development, and therapy of cardiovascular diseases. Increasing evidence suggests that AhR is involved in maintaining homeostasis or in triggering pathogenesis by modulating the biological responses of critical cell types in the cardiovascular system. Here, we describe the structure, distribution, and ligands of AhR and the AhR signaling pathway and review the impact of AhR on cardiovascular physiology. We also discuss the potential contribution of AhR as a new potential factor in the targeted treatment of cardiovascular diseases