A broad-spectrum integrative design for cancer prevention and therapy: The challenge ahead

AbstractDespite exciting advances in targeted therapies, high drug costs, marginal therapeutic benefits and notable toxicities are concerning aspects of today's cancer treatments. This special issue of Seminars in Cancer Biology proposes a broad-spectrum, integrative therapeutic model to complement targeted therapies. Based on extensive reviews of the cancer hallmarks, this model selects multiple high-priority targets for each hallmark, to be approached with combinations of low-toxicity, low-cost therapeutics, including phytochemicals, adapted to the well-known complexity and heterogeneity of malignancy. A global consortium of researchers has been assembled to advance this concept, which is especially relevant in an era of rapidly expanding capacity for genomic tumor analyses, alongside alarming growth in cancer morbidity and mortality in low- and middle-income nations

Natural Products for Cancer Prevention and Therapy

ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms. [This Special Issue book, “Natural Products for Cancer Prevention and Therapy”, is based on recent advances in natural products for cancer prevention and therapy. For this purpose, the authors of this book have been organizing a biennial international conference series. The first meeting (First International Conference on Natural Products for Cancer Prevention and Therapy) was held in Istanbul between 31 August and 2 September 2015, with the support and contribution of many valuable researchers in this field. The abstracts of the first conference were published in the Anticancer Drugs journal as a supplement. The second meeting, namely The Second International Conference on Natural Products for Cancer Prevention and Therapy, was held at Erciyes University, Kayseri, Turkey, between 8 and 11 November 2017. The abstracts of all of the presentations from the second meeting were published in the Special Issue of Proceedings by the MDPI publishing group. Furthermore, the conference report and the selected full-length papers based on the presentations at the meeting, as well as other papers based on natural products for cancer prevention and therapy, were published as a Special Issue of the Nutrients journal from MDPI. This Special Issue has contributions from various participants of the aforementioned conference, as well as other cancer and natural product researchers. These contributions include original research papers, authoritative and up-to-date reviews, and commentaries on the following topics and areas: •Natural products for the prevention and therapy of oncologic diseases •Mechanism of natural agents for anticancer and cancer preventive effects •In vitro, in vivo, and clinical studies related to natural agents and cancer • Combinatorial effects of phytochemicals and cancer chemotherapeutic drugs •Challenges and innovative approaches for anticancer drug development based on natural products •Emerging studies on anticancer phytochemicals

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Human exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been sug-gested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by poly- phenols. Plant-derived polyphenols, such as epigallocatechin-gallate, resveratrol, curcumin and anthocyanins reduce the incidence of cancer and can be useful nutraceuticals for alleviating the detrimental outcomes of harmful pollutants. However, development of therapies based on polyphenol administration requires further studies to validate the biological efficacy, identifying effective doses, mode of action and new delivery forms. Innovative microphysiological testing models are presented and specific proposals for future trials are given. Merging the current knowledge of multifactorial actions of specific polyphenols and chief environmental toxi- cants, this work aims to potentiate the delivery of phytochemical-based protective treatments to individuals at high-risk due to environmental exposure.info:eu-repo/semantics/publishedVersio

Elevated Lipid Peroxidation, Decreased Glutathione Levels and Changes in Glutathione-Related Enzymes in Rats Treated with Human PIacental Extract

The in vivo effects of human placental extract (1-4 ml/kg) on hepatic lipid peroxidation, blood and liver glutathione (GSH) levels and several enzymes associated with the antioxidant defence mechanism; i.e., catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, together with some blood biochemical responses were investigated in rats. At an optimal dose level (4 ml/kg), a single acute intraperitoneal administration of the extract caused a significant enhancement (49.9%; p &#60; 0.001) of lipid peroxidation with a decline in GSH level both in blood (45.1%; p &#60; 0.001) and liver (61.0%; p &#60; 0.001) in comparison to control animals. Activities of catalase, glutathione peroxidase and glutathione reductase were inhibited in a dose-responsive way by the treatment with the extract which also increased the activity of glutathione S-transferase in a dose-dependent manner. The extract was found to be hepatotoxic in terms of elevation of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum lactate dehydrogenase and blood methemoglobin concentration. Results of this study suggest the adverse consequences of the administration of the extract due to its substantial ability to alter normal cellular processes.</p

Assessing Health Conditions and Medication Use Among the Homeless Community in Long Beach, California

Objective: Persons experiencing homelessness are a vulnerable population and are at increased risk for morbidity and all-cause mortality compared to the general population. This study sought to evaluate medication use, regular physician visits, and identify health conditions among the homeless population of Long Beach, California. Methods: Two brown bag medication review events were held at homeless shelters in the Long Beach area. Demographic information, medication use, and comorbid disease states were obtained through surveys. Findings: Three-fourths of the cohort (95 participants) consisted of males, and the average age of participants was 48 years. Psychiatric disorders and cardiovascular disease were the most common disease states reported at 32% and 46%, respectively and so were medications used in treating these chronic diseases. Medication adherence was found to be a significant problem in this population, where more than 30% of patients were nonadherent to medications for chronic diseases. Furthermore, foot problems, hearing and vision difficulties constitute the most commonly overlooked health problems within the homeless population. Conclusion: Based on this and other similar finding, we must accept that the homeless represent a vulnerable population, and that because of this fact, more programs should be focused at improving availability and access to health care among the homeless. Regarding the high number of reported health problems in the study, more studies are needed and more studies should incorporate screening for foot, hearing, and vision issues, both to increase awareness and to provide an opportunity for devising possible solutions to these highly preventable conditions

Oleuropein and Cancer Chemoprevention: the Link is Hot

Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.This article is the outcome of an in-house financially non-supported study. A. Sureda was partially supported by the Spanish Ministry of Health, Social Services and Equality (CIBEROBN-B12/03/30038). A. Mocan acknowledges funding from UEFISCDI, Romania, project no. PNII-RU-TE-2014-4-1247.info:eu-repo/semantics/publishedVersio

Therapeutic targets of natural products for the management of cardiovascular symptoms of coronavirus disease 2019

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first occurred in China in December 2019 and subsequently spread all over the world with cardiovascular, renal, and pulmonary symptoms. Therefore, recognizing and treating the cardiovascular sign and symptoms that caused by coronavirus disease 2019 (COVID-19) can be effective in reducing patient mortality. To control the COVID-19-related cardiovascular symptoms, natural products are considered one of the promising choices as complementary medicine. Scientists are struggling to discover new antiviral agents specific to this virus. In this review, the natural products for management of cardiovascular symptoms of COVID-19 are categorized into three groups: (a) natural products with an impact on angiotensin II type 1 receptor; (b) natural products that inhibit angiotensin-converting enzyme activity; and (c) natural products that mimic adenosine activity. All these natural products should undergo clinical investigations to test their efficacy, safety, and toxicity in the treatment of cardiovascular symptoms of COVID-19. This article summarizes agents with potential efficacy against COVID-19-related cardiovascular symptoms

Infections and immunity: associations with obesity and related metabolic disorders

About one-fourth of the global population is either overweight or obese, both of which increase the risk of insulin resistance, cardiovascular diseases, and infections. In obesity, both immune cells and adipocytes produce an excess of pro-inflammatory cytokines that may play a significant role in disease progression. In the recent coronavirus disease 2019 (COVID-19) pandemic, important pathological characteristics such as involvement of the renin-angiotensin-aldosterone system, endothelial injury, and pro-inflammatory cytokine release have been shown to be connected with obesity and associated sequelae such as insulin resistance/type 2 diabetes and hypertension. This pathological connection may explain the severity of COVID-19 in patients with metabolic disorders. Many studies have also reported an association between type 2 diabetes and persistent viral infections. Similarly, diabetes favors the growth of various microorganisms including protozoal pathogens as well as opportunistic bacteria and fungi. Furthermore, diabetes is a risk factor for a number of prion-like diseases. There is also an interesting relationship between helminths and type 2 diabetes; helminthiasis may reduce the pro-inflammatory state, but is also associated with type 2 diabetes or even neoplastic processes. Several studies have also documented altered circulating levels of neutrophils, lymphocytes, and monocytes in obesity, which likely modifies vaccine effectiveness. Timely monitoring of inflammatory markers (e.g., C-reactive protein) and energy homeostasis markers (e.g., leptin) could be helpful in preventing many obesity-related diseases

Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor cells by the immune system, thereby diminishing tumor immunity. The argument for employing epigenetic drugs in the treatment of acute myeloid leukemia (AML) patients is supported by evidence that both epigenetic changes and mutations in the epigenetic machinery contribute to AML etiology. Although hypomethylating drugs have been licensed for use in AML, additional epigenetic inhibitors, such as HDACis, are now being tested in humans. Preclinical studies evaluating the efficacy of HDACis against AML have shown the ability of specific agents, such as anobinostat, vorinostat, and tricostatin A, to induce growth arrest, apoptosis, autophagy and cell death. However, these inhibitors do not seem to be successful as monotherapies, but instead achieve results when used in conjunction with other medications. In this article, we discuss the mounting evidence that HDACis promote extensive histone acetylation, as well as substantial increases in reactive oxygen species and DNA damage in hematological malignant cells. We also evaluate the potential of various natural product-based HDACis as therapeutic agents to combat hematological malignancies