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Both Asia and Africa are home to many plants that can be used for the treatment of many diseases and their medicinal properties are gaining interest in western societies. Medicinal plants from Asia and Africa are used for their healing abilities and also have a symbolic meaning in communities.The importance of traditional autochthonous plant remedies plays a crucial role in the health of millions of people of these two continents. Even today, traditional medicine represents the dominant medical system for millions of people showing a significant impact on health care practices. Therefore, traditional operators still represent a vital part of regional healthcare systems. For this reason, pharmaceutical industries consider traditional medicine as a source for the identification of bioactive compounds that can be used in the preparation of synthetic drugs.Biologically Active Natural Products from Asia and Africa: A Selection of Topics guides the reader toinformation about new natural products from these regions and the different ways to use them to treat or alleviate many of the most common diseases. The volume presents nine topics covering a number of facets of natural product medicine including: - pharmaceutical analysis of anti-diabetic herbal medicines from Bangladesh and local retailers- caffeine intake and the risk of female infertility- pharmaceutical analysis of Urena sinuata (bur mallow)- anti-CHIKV activities of diterpenes and their derivatives- anti-inflammatory nanogel for the treatment of psoriasis- antlithiatic properties of Moroccan medicinal plants- ethnobotanic, phytochemical and biological activities of Aristolochia longa L. (pipevine)- wound healing potential of combined extracts of stem bark and leaves of sphenocentrum jollyanum (an African shrub) This is a handy reference for specialists and R&D experts in pharmaceutical chemistry who wish to be informed about current knowledge on developing natural remedies in Asia and Africa.

Lycopene is a pigment belonging to the group of carotenoids and it is among the most carefully studied antioxidants found especially in fruit and vegetables. As a carotenoid, lycopene exerts beneficial effects on human health by protecting lipids, proteins, and DNA from damage by oxidation. Lycopene is a powerful oxygen inactivator in the singlet state. This is suggestive of the fact that lycopene harbors comparatively stronger antioxidant properties over other carotenoids normally present in plasma. Lycopene is also reported to hinder cancer cell proliferation. The uncontrolled, rapid division of cells is a characteristic of the metabolism of cancer cells. Evidently, lycopene causes a delay in the progression of the cell cycle, which explains its antitumor activity. Furthermore, lycopene can block cell transformation by reducing the loss of contact inhibition of cancer cells. This paper collects recent studies of scientific evidence that show the multiple beneficial properties of lycopene, which acts with different molecular and cellular mechanisms.

Key Points Several aspects of the design of phase I trials have evolved in the era of molecular targeted agents to enable better assessment of these novel therapies and maximize the efficiency of drug development Current phase I trial designs increasingly use new dose-escalation approaches and biomarker-driven patient selection, while expanding study objectives to include efficacy evaluation and pharmacokinetics/ pharmacodynamics (PK/PD), in addition to safety Preclinical evidence supporting a biological or pharmacological rationale and exploration of PK/PD interactions between drug partners are necessary for phase I trials of combination therapies that include targeted agents Changes to the regulatory approval process help to expedite drug development, particularly for novel agents with a well-established biological mechanism, a predictive biomarker, and clear evidence of efficacy in early trials Changes in the goals and conduct of phase I trials have resulted in a shift towards multi-institutional studies and centralized management, with a significant impact on the structure of phase I programmes Both the efficiency and rate of drug approval need to improve despite the limited acceptance of novel trial designs and difficulties associated with early phase biomarker integration The improved understanding of the molecular mechanisms that drive tumorigenesis has led to the development of molecularly targeted agents (MTAs) that inhibit specific proteins or pathways. However, the rate of drug approvals remains disappointingly low in oncology. The authors of this Review discuss several aspects of phase I trials that are evolving in the MTA era in order to adapt to the changing nature of cancer therapies and to expedite their clinical translation. Advances in our knowledge of the molecular pathogenesis of cancer have led to increased interest in molecularly targeted agents (MTAs), which target specific oncogenic drivers and are now a major focus of cancer drug development. MTAs differ from traditional cytotoxic agents in various aspects, including their toxicity profiles and the potential availability of predictive biomarkers of response. The landscape of phase I oncology trials is evolving to adapt to these novel therapies and to improve the efficiency of drug development. In this Review, we discuss new strategies used in phase I trial design, such as novel dose-escalation schemes to circumvent limitations of the classic 3 + 3 design and enable faster dose escalation and/or more-precise dose determinations using statistical modelling; improved selection of patients based on genetic or molecular biomarkers; pharmacokinetic and pharmacodynamic analyses; and the early evaluation of efficacy — in addition to safety. Indeed, new expedited approval pathways that can accelerate drug development require demonstration of efficacy in early phase trials. The application of molecular tumour profiling for matched therapy and the testing of drug combinations based on a strong biological rationale are also increasingly seen in phase I studies. Finally, the shift towards multi-institutional trials and centralized study management results in consequent implications for institutions and investigators. These issues are also highlighted herein.

The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

Background Post-transplant malignancies are one of the leading causes of morbidity, mortality and graft failure in kidney transplant recipients (KTRs). While viral infections and immunosuppressive drugs have historically been considered primary causes, the mechanisms underlying post-transplant cancer occurrence remain incompletely understood. Furthermore, predictive cancer biomarkers have yet to be identified in KTRs. Methods COMETA study is an observational study involving 138 KTRs, and it aims to elucidate the interplay between the immune system and cancer by integrating comprehensive clinical data with high-throughput small-RNA sequencing on the serum of patients with post-kidney transplant malignancies. Results Our results identified three distinct serum miRNA profiles, respectively, associated with kidney transplantation, pro-oncogenic and onco-protective factors in this unique population. These profiles were also used to create miRNA classifiers, which demonstrated promising predictive performance, especially for tumor-promoting signatures. Notably, miR-210-3p up-regulation, within the cancer-related profile was first found to be associated with non-melanoma skin cancer. Conclusion These findings could serve as a basis for future research, paving the way for the development of advanced tools for early cancer diagnosis, precise prognosis formulation, and the creation of targeted therapies for KTRs with neoplastic complications.

Recent developments in pre-clinical screening tools, that more reliably predict the clinical effects and adverse events of candidate therapeutic agents, has ushered in a new era of drug development and screening. However, given the rapid pace with which these models have emerged, the individual merits of these translational research tools warrant careful evaluation in order to furnish clinical researchers with appropriate information to conduct pre-clinical screening in an accelerated and rational manner. This review assesses the predictive utility of both well-established and emerging pre-clinical methods in terms of their suitability as a screening platform for treatment response, ability to represent pharmacodynamic and pharmacokinetic drug properties, and lastly debates the translational limitations and benefits of these models. To this end, we will describe the current literature on cell culture, organoids, in vivo mouse models, and in silico computational approaches. Particular focus will be devoted to discussing gaps and unmet needs in the literature as well as current advancements and innovations achieved in the field, such as co-clinical trials and future avenues for refinement.

Depression and obesity are very common pathologies. Both cause significant problems of both morbidity and mortality and have decisive impacts not only on the health and well-being of patients, but also on socioeconomic and health expenditure aspects. Many epidemiological studies, clinical studies and meta-analyses support the association between mood disorders and obesity in relationships to different conditions such as the severity of depression, the severity of obesity, gender, socioeconomic status, genetic susceptibility, environmental influences and adverse experiences of childhood. Currently, both depression and obesity are considered pathologies with a high-inflammatory impact; it is believed that several overlapping factors, such as the activation of the cortico-adrenal axis, the exaggerated and prolonged response of the innate immune system and proinflammatory cytokines to stress factors and pathogens—as well as alterations of the intestinal microbiota which promote intestinal permeability—can favor the expression of an increasingly proinflammatory phenotype that can be considered a key and common phenomenon between these two widespread pathologies. The purpose of this literature review is to evaluate the common and interacting mechanisms between depression and obesity.

Background Triple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC. Methods This dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients. Results Forty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6–32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14–45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations. Conclusions Single-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies. Trial registration ClinicalTrials.gov, NCT01639248 . Registered on July 12, 2012.

Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.