5-Aza-2′-deoxycytidine stress response and apoptosis in prostate cancer

While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of –CpG– cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2′-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGFβR1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 μM) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis)

Tillage and nutrient management influence net global warming potential and greenhouse gas intensity in soybean-wheat cropping system

207-214Conservation tillage has proven advantageous in improving soil health and productivity. However, the greenhouse gases (GHGs) emission and intensity from different conservation tillage and nutrient management systems under Indian conditions are less understood. Therefore, here, we compared the effect of tillage and nutrient management on GHGs emissions, net global warming potential (NGWP), and greenhouse gas intensity (GHGI) from a field experiment under five years in a soybean-wheat cropping system in the Vertisols. The tillage treatments comprised of reduced tillage (RT) and no tillage (NT). The three nutrient management treatments included application of 100% NPK (T1), 100% NPK + 1.0 Mg FYM-C ha-1 (T2), 100% NPK +2.0 Mg FYM-C ha-1 (T3). The results showed significantly higher SOC sequestration under NT (1388 kg ha-1 yr-1) followed byRT (1134 kg ha-1 yr-1) with application of FYM (2.0 Mg C ha-1) (T3) every year. Across tillage, integrated nutrient management(T2 and T3) lowered NGWP and GHGI compared to NPK (T1). The GHGI of NT system was less by 33% compared to RT. The results suggest that GHGs mitigation and sustained food production in the soybean-wheat system can be achieved in NT and RT with integrated use of organic and inorganic fertilizer as the major component of nutrient management

Therapeutic applications of curcumin nanomedicine formulations in cardiovascular diseases

Cardiovascular diseases (CVD) compromises a group of heart and blood vessels disorders with high impact on human health and wellbeing. Curcumin (CUR) have demonstrated beneficial effects on these group of diseases that represent a global burden with a prevalence that continues increasing progressively. Pre- and clinical studies have demonstrated the CUR effects in CVD through its anti-hypercholesterolemic and anti-atherosclerotic effects and its protective properties against cardiac ischemia and reperfusion. However, the CUR therapeutic limitation is its bioavailability. New CUR nanomedicine formulations are developed to solve this problem. The present article aims to discuss different studies and approaches looking into the promising role of nanotechnology-based drug delivery systems to deliver CUR and its derivatives in CVD treatment, with an emphasis on their formulation properties, experimental evidence, bioactivity, as well as challenges and opportunities in developing these systems.This work was supported by CONICYT PIA/APOYO CCTE AFB170007. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT–Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020—Programa Operacional Regional do Norte” (NORTE-01-0145-FEDER-000012)

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-a, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1G1A1004667), Republic of Korea

Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions

The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states

High Resolution Detection and Analysis of CpG Dinucleotides Methylation Using MBD-Seq Technology

Methyl-CpG binding domain protein sequencing (MBD-seq) is widely used to survey DNA methylation patterns. However, the optimal experimental parameters for MBD-seq remain unclear and the data analysis remains challenging. In this study, we generated high depth MBD-seq data in MCF-7 cell and developed a bi-asymmetric-Laplace model (BALM) to perform data analysis. We found that optimal efficiency of MBD-seq experiments was achieved by sequencing ∼100 million unique mapped tags from a combination of 500 mM and 1000 mM salt concentration elution in MCF-7 cells. Clonal bisulfite sequencing results showed that the methylation status of each CpG dinucleotides in the tested regions was accurately detected with high resolution using the proposed model. These results demonstrated the combination of MBD-seq and BALM could serve as a useful tool to investigate DNA methylome due to its low cost, high specificity, efficiency and resolution

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

Leishmaniasis, a neglected tropical disease (NTD) caused by Leishmania, has been put on the World Health Organization agenda for eradication as a part of their Special Programme for Tropical Diseases Research. Visceral leishmaniasis (VL) is a life-threatening disease when no treatment is given. Most of the drugs still used to treat VL are often expensive, difficult to administer, have serious side effects, and several are becoming ineffective because of increasing parasite resistance. Cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. We have for the first time characterized the in vivo effect of cisplatin in murine experimental visceral leishmaniasis, but at higher doses it is nephrotoxic. Considering the above findings, the present study was designed to evaluate the protective efficacy of the drug in combination with various antioxidants to reduce or prevent cisplatin-induced nephrotoxicity. Drug treatment induces a higher secretion of Th1 cytokines, diminution in parasite burden, and the supplementation of antioxidants which are antagonists of the toxicity helps in reducing the nephrotoxicity