Potential applications of antofine and its synthetic derivatives in cancer therapy: structural and molecular insights.

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure-activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments.

Optimizing Public Health Preparedness for Highly Infectious Diseases in Central Vietnam.

Our primary objectives were (a) to determine the need for and the availability of point-of-care testing (POCT) for infectious diseases and (b) to recommend point-of-care testing strategies and Spatial Care PathsTM (SCPs) that enhance public health preparedness in the regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in seven community health centers (CHCs), seven district hospitals (DHs) and one provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: six of seven CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (tuberculosis and syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher-tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients' homes and in primary care settings for the early detection of infected individuals and the mitigation of the spread of new COVID-19 variants and other highly infectious diseases.

Iloprost Attenuates Oxidative Stress-Dependent Activation of Collagen Synthesis Induced by Sera from Scleroderma Patients in Human Pulmonary Microvascular Endothelial Cells.

Endothelial cell injury is an early event in systemic sclerosis (SSc) pathogenesis and several studies indicate oxidative stress as the trigger of SSc-associated vasculopathy. Here, we show that circulating factors present in sera of SSc patients increased reactive oxygen species (ROS) production and collagen synthesis in human pulmonary microvascular endothelial cells (HPMECs). In addition, the possibility that iloprost, a drug commonly used in SSc therapy, might modulate the above-mentioned biological phenomena has been also investigated. In this regard, as compared to sera of SSc patients, sera of iloprost-treated SSc patients failed to increased ROS levels and collagen synthesis in HPMEC, suggesting a potential antioxidant mechanism of this drug.

Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety.

Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb-drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.

A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis.

Systemic sclerosis (SSc), an autoimmune disease that is associated with a number of genetic and environmental risk factors, is characterized by progressive fibrosis and microvasculature damage in the skin, lungs, heart, digestive system, kidneys, muscles, joints, and nervous system. These abnormalities are associated with altered secretion of growth factor and profibrotic cytokines, such as transforming growth factor-beta (TGF-ß), interleukin-4 (IL-4), platelet-derived growth factor (PDGF), and connective-tissue growth factor (CTGF). Among the cellular responses to this proinflammatory environment, the endothelial cells phenotypic conversion into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndMT), has been postulated. Reactive oxygen species (ROS) might play a key role in SSs-associated fibrosis and vascular damage by mediating and/or activating TGF-ß-induced EndMT, a phenomenon that has been observed in other disease models. In this review, we identified and critically appraised published studies investigating associations ROS and EndMT and the presence of EndMT in SSc, highlighting a potential link between oxidative stress and EndMT in this condition.

Oxidative stress-induced Akt downregulation mediates green tea toxicity towards prostate cancer cells.

Green tea consumption has been shown to possess cancer chemopreventive activity. Polyphenol E (PE) is a widely used standardized green tea extract formulation. This study was designed to investigate the impact of PE on prostate cancer cells (PC3), analyze the potential signals involved and elucidate whether anti- or pro-oxidant effects may be implicated. Treatment of PC3 cells with 30 and 100µg/ml PE significantly decreased cell viability and proliferation. At the tested concentrations, PE did not exert any antioxidant activity, eliciting instead a pro-oxidant effect at concentrations 30 and 100µg/ml, which was consistent with the observed PE cytotoxicity. PE-induced cell death was associated with mitochondrial dysfunction and downregulation of Akt activation, thus suggesting their implication in the PE-elicited cell dysfunction. Cell exposure to the ROS scavenger N-Acetyl Cysteine prevented PE-induced ROS increase, pAkt impairment, and cell death, clearly indicating the causative role of ROS in the observed phenomena. Failure of PE to induce PC3 damage in cells overexpressing Akt further confirms its implication in the PE-elicited cell death. Our findings showed an association between the antiproliferative and the pro-oxidant effect elicited by PE on PC3 cells and delineates a molecular signaling pattern potentially implicated in the toxicity of PE towards prostate cancer cells.