Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides.

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K-->Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases

An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey and a Consensus Meeting

Funding/Support and role of the sponsor: This study was supported by the General Research Fund/Early Career Scheme of the Research Grants Council, Hong Kong, China (reference no. 24116518).Peer reviewedPostprin

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A review of the cardiovascular benefits and antioxidant properties of allicin

Cardiovascular disease (CVD) is a category of chronic noncommunicable diseases causing high global mortality and has been a heavy social burden in many countries. In the search of chemicals that arise from natural food source, allicin is one such ingredient from garlic that was discovered with the potential to provide beneficial effects to the cardiovascular system. From the pharmacokinetic studies, allicin is known to be hydrophobic and can be readily absorbed through the cell membrane without inducing any damage to the phospholipid bilayer and then rapidly metabolized to exert pharmacological effects that are important to the cardiovascular system. It was found to provide cardio-protective effects by inducing vasorelaxation and alleviating various pathological conditions of CVD, including cardiac hypertrophy, angiogenesis, platelet aggregation, hyperlipidemia and hyperglycemia. Allicin was also discovered to further protect the cardiovascular system by enhancing the antioxidant status by lowering the level of reactive oxygen species and stimulating the production of glutathione. Other pharmacological benefits such as anticancer and antimicrobial activities were also discussed. It is concluded that allicin can be potentially developed into a health product for the cardiovascular system

Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides.

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K-->Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases

Immune Checkpoints Inhibitors and Chemotherapy as First-Line Treatment for Metastatic Urothelial Carcinoma: A Network Meta-Analysis of Randomized Phase III Clinical Trials

Immune checkpoints inhibitors (ICIs) were considered as second-line treatments in metastatic urothelial carcinoma (mUC) based on better survival benefit and safety profile than chemotherapy (CTX). We aimed to assess different ICIs regimens in the efficacy and safety for front-line treatments in mUC patients. A comprehensive literature search was performed and Phase II-III randomized controlled trials (RCTs) on ICIs for patients with mUC were included. The outcome was evaluated by overall survival (OS), progression of free survival (PFS), objective response rate (ORR), and grade 3–5 adverse events. Network meta-analysis was used to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were applied to rank the included treatments for each outcome. Results: The survival benefit of a single ICI was non-inferiority to chemotherapy (CTX). Although no superior effects were indicated, combination therapy (either ICIs plus CTX or ICIs plus ICIs) presented better OS compared with CTX alone. In terms of PFS, combination therapy produced a noticeable benefit over CTX. Regarding the SUCRA ranking, atezolizumab plus CTX was associated with the best ranking for OS and pembrolizumab plus CTX was the best in PFS. In terms of safety, a single ICI had better safety profile than CTX and combination therapy had a similar risk of grade 3–5 adverse events with CTX. Conclusions: Our NMA results revealed that combination therapy has better ranking compared with monotherapy in OS and acceptable AEs. ICIs alone present non-inferior OS but a lower incidence of AEs compared with CTX

Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients – a network meta-analysis

Abstract Background Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients. Methods A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome. Results A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition. Conclusions BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications

A review of the phytochemistry and pharmacological activities of raphani semen

The dried ripe seed of Raphanus sativus L., commonly known as radish seed (or Raphani Semen), is used as traditional Chinese medicine (TCM) to treat constipation, chronic tracheitis, and hypertension. The major active compounds in Raphani Semen are alkaloids, glucosinolates, brassinosteroids, and flavonoids. Fatty acids are its main nutritional contents. Raphani Semen has been demonstrated to have beneficial effects on hypertension, obesity, diabetes mellitus, constipation, and cough. So far, there is no report about the adverse/toxic effects of this herb on humans. However, Raphani Semen processed by roasting was reported to exhibit some adverse effects on mice. Additionally, erucic acid, the main fatty acid in Raphani Semen, was shown to enhance the toxicity of doxorubicin. Thus, Raphani Semen has a potential risk of causing toxicity and drug interaction. In summary, Raphani Semen is a valuable TCM herb with multiple pharmacological effects. More studies on Raphani Semen could help better understand its pharmacological mechanisms so as to provide clear scientific evidence to explain its traditional uses, to identify its therapeutic potential on other diseases, and to understand its possible harmful effects