Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer.

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.

Tumor mutational burden as a predictive biomarker for non-small cell lung cancer treated with immune checkpoint inhibitors of PD-1/PD-L1.

BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.

[Study on the chemical constituents of Viscum ovalifolium].

OBJECTIVE: To study the chemical constituents of Viscum ovalifolium. METHODS: The chemical constituents from Viscum ovalifolium were isolated and purified by silica gel column chromatography, polyamide column chromatography and recrystallization methods. Their structures were elucidated by physicochemical properties and spectral analysis. RESULTS: Twelve compounds were isolated and their structures were identified as 1-octadecene (1), ethyl palmitate (2), 28-hydrxy-amyrone (3), betulinic acid (4), rutin (5), quercetin (6), beta-amyrinpalmitate (7), lupeol acetate (8), beta-amyrin (9), beta-sitosterol (10), lupeol (11) and oleanolic acid (12). CONCLUSION: Compounds 1 - 6 are obtained from this plant for the first time.

[Morphological identification of 20 medicinal species in Hypericum].

OBJECTIVE: To provide anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum. METHOD: Morphological and anatomical study on the organs of 20 medicinal species in Hypericum using tissue clearing, paraffin sectioning and thin sectioning. RESULT: According to their anatomical characteristics, the secretory structures can be divided into nodules, secretory cavities (canals) and tiny secretory tubes of 20 medicinal species in Hypericum. Hypericin was produced and stored in the nodules, while the volatile oil was produced and stored in the secretory cavities (canals) and tiny secretory tubes. The types differed markedly from each other in location, diameter and distributional density of leaf, and the anatomical structures differed from each other of stem, calyx, petal, anther and fruit among the 20 species in Hypericum. CONCLUSION: The secretory structures may be as anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum.

Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke.

Cerebrovascular disease such as stroke is one of the most common diseases in the aging population, and neural stem cells (NSCs) transplantation may provide an alternative therapy for cerebral ischemia. However, a hostile microenvironment in the ischemic brain offers is challenging for the survival of the transplanted cells. Considering the neuroprotective role of basic fibroblast growth factor (bFGF), the present study investigated whether bFGF gene-modified NSCs could improve the neurological function deficit after transient middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. These rats were intravenously injected with modified NSCs (5×106/200 µL) or vehicle 24 h after MCAO. Histological analysis was performed on days 7 and 28 after tMCAO. The survival, migration, proliferation, and differentiation of the transplanted modified C17.2 cells in the brain were improved. In addition, the intravenous infusion of NSCs and bFGF gene-modified C17.2 cells improved the functional recovery as compared to the control. Furthermore, bFGF promoted the C17.2 cell growth, survival, and differentiation into mature neurons within the infarct region. These data suggested that bFGF gene-modified NSCs have the potential to be a therapeutic agent in brain ischemia.

Comparison of the more than 5-year clinical outcomes of cervical disc arthroplasty versus anterior cervical discectomy and fusion: A protocol for a systematic review and meta-analysis of prospective randomized controlled trials.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) was almost the "golden standard" technique in treatment of symptomatic cervical degenerative disc disease, however, it cause motion loss of the indexed level, increase the intradiscal pressure and motion of the adjacent levels, and may accelerate the degeneration of adjacent level. Cervical disc arthroplasty (CDA) was designed to preserve the motion of index level, avoid the over-activity of adjacent levels and reduce the degeneration of adjacent disc levels, the process of degeneration of adjacent level is very slowly, long term follow up studies should be conducted, this study aim to compare the more than 5 years' long-term clinical outcomes and safety between CDA and ACDF. METHODS: A systematic review and meta-analysis that will be performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The electric database of Medline, Embase, and Cochrane library will be systematic search. A standard data form will be used to extract the data of included studies. We will assess the studies according to the Cochrane Handbook for Systematic Reviews of Interventions, and perform analysis in software STATA 12.0. Fixed-effects models will be used for homogeneity data, while random-effects will be used for heterogeneity data. The overall effect sizes will be determined as weighted mean difference (WMD) for continuous outcomes and Relative risk (RR) for dichotomous outcomes. RESULTS: The results of study will be disseminated via both international conference and peer-review journal. CONCLUSION: The conclusion of our study will provide the long-term and updated evidence of clinical outcomes and safety between CDA and ACDF, and help surgeon to change better surgical technique for patients.