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A study was conducted during the period from 20 September, 2015 to 14 November, 2015 to determine the prevalence and therapeutic assessment of bovine fascioliosis at Bauphal Upazilla under Patuakhali district in Bangladesh. A total of 85 bovine cases were considered for the present study. The overall prevalence of fascioliosis was 54.12 (%). The age of the study population were divided in three groups i.e. < 3 years; 3-5 years; >5 years with the prevalence(%) of fascioliosis were 47.06 %, 54.06% and 71.43% respectively. Among the study population the higher prevalence was recorded in female 56.52% followed by male 51.28%. The prevalence (%) was higher in cross bred 58.54% than the local 50.00% cattle. Although this study period and sample size were very small, but the result of the present study will help to establish better treatment and control strategy against fascioliosis in cattle. [ABSTRACT FROM AUTHOR]

Abstract Background Mithun (Bos frontalis), also called gayal, is an endangered bovine species, under the tribe bovini with 2n = 58 XX chromosome complements and reared under the tropical rain forests region of India, China, Myanmar, Bhutan and Bangladesh. However, the origin of this species is still disputed and information on its genomic architecture is scanty so far. We trust that availability of its whole genome sequence data and assembly will greatly solve this problem and help to generate many information including phylogenetic status of mithun. Recently, the first genome assembly of gayal, mithun of Chinese origin, was published. However, an improved reference genome assembly would still benefit in understanding genetic variation in mithun populations reared under diverse geographical locations and for building a superior consensus assembly. We, therefore, performed deep sequencing of the genome of an adult female mithun from India, assembled and annotated its genome and performed extensive bioinformatic analyses to produce a superior de novo genome assembly of mithun. Results We generated ≈300 Gigabyte (Gb) raw reads from whole-genome deep sequencing platforms and assembled the sequence data using a hybrid assembly strategy to create a high quality de novo assembly of mithun with 96% recovered as per BUSCO analysis. The final genome assembly has a total length of 3.0 Gb, contains 5,015 scaffolds with an N50 value of 1 Mb. Repeat sequences constitute around 43.66% of the assembly. The genomic alignments between mithun to cattle showed that their genomes, as expected, are highly conserved. Gene annotation identified 28,044 protein-coding genes presented in mithun genome. The gene orthologous groups of mithun showed a high degree of similarity in comparison with other species, while fewer mithun specific coding sequences were found compared to those in cattle. Conclusion Here we presented the first de novo draft genome assembly of Indian mithun having better coverage, less fragmented, better annotated, and constitutes a reasonably complete assembly compared to the previously published gayal genome. This comprehensive assembly unravelled the genomic architecture of mithun to a great extent and will provide a reference genome assembly to research community to elucidate the evolutionary history of mithun across its distinct geographical locations.

Mithun (Bos frontalis) or gayal and Indian Bison or wild gaur (Bos gaurus) are listed among the rare and endangered bovine species of India. The remote location of mithun in four North Eastern Hill states (Arunachal Pradesh, Nagaland, Manipur, and Mizoram), scattered population size, and non-availability of genetic diversity status are major limitations towards devising a suitable breeding and conservation policy of these species. Since several studies have demonstrated the successful applicability of microsatellite/SSR markers across related genera/families in both crop plants and animal species, 30 FAO recommended cattle microsatellites were utilized for the assessment of the genetic diversity of Indian mithun, bison, and local Tho-tho cattle. Mitochondrial transmembrane protein coding cytochrome B (CYTB) complete sequence data of 71 bovine samples from India were also used to reinforce the study. Population structuring clustered the all bovines into three subgroups as per geographical location and species. Bottleneck analysis indicated a mode shift in the allelic frequency distribution of gaur, indicating minor genetic bottleneck events in the past, while no bottleneck was found in mithun and Tho-tho cattle. To our knowledge, this study represents the first report of molecular genetic characterization showing the population structure and status of genetic diversity in rare Indian bovines, namely, Mithun, Gaur, and Tho-tho cattle.

Oyster mushrooms (Pleurotus spp.) are widely cultivated all over the world. Its production is remarkably affected by the environmental conditions like temperature and relative humidity. In this study, we investigated the production of four species of oyster mushroom: Pleurotus ostreatus, P. florida, P. sajor-caju and P. high king cultivated in every season (January to December) in Bangladesh. The temperature (in °C) and relative humidity (% RH) of culture house in each month, and parameters of mushroom production were recorded. In all of the selected species of this study, the minimum days required for primordial initiation, and the maximum number of fruiting bodies, biological yield and biological efficiency were found during December to February (14-27 °C, 70-80% RH). The production was found minimum during the cultivated time August to October. We suggest cultivation of selected Pleurotus spp. in winter (temperature zone 14-27 °C with relative humidity 70-80%) for better production and biological efficiency. [ABSTRACT FROM AUTHOR]

Background: Maternal health, in terms of pregnancy and childbirth, is an important aspect of women's reproductive health and remains a public health concern in underdeveloped countries of the world. Reproductive health care seeking behavior (RHSB), in both men and women in society, is influenced by a variety of social and environmental factors that needs to be summarized., Objectives: This review aims to enhance understanding and perception of services in relation to RHSBs in several domains such as antenatal care (ANC), delivery care, postnatal care (PNC), and family planning (FP) services, for married women of reproductive age in Bangladesh., Search Strategy: In major databases, for example, Medline, Ovid, PubMed, Web of Science, ProQuest and Google Scholar following keywords, timeline set as 2010 up to December 30, 2022., Selection Criteria: Articles that included discussion on married women of reproductive age, and their type of care seeking behavior for reproductive health., Data Collection and Analysis: A systematic literature search was carried out and expected outcome was health care seeking behavior in the aspects of ANC, delivery care, PNC, and FP services. A data extraction form and quality appraisal form were used for data on RHSB of married women of the reproductive age group in Bangladesh and associated factors., Main Results: A total of 245 articles were retrieved from databases; stepwise screening was done and finally 23 full-text articles were included for analysis. Descriptive statistics were used based on the included articles for narrative synthesis. In the selected articles, 17 (73.91%) were cross-sectional studies and more than half discussed both urban and rural women. Ante- and postnatal visits have proven to have positively influenced overall RHSB, as seen in Bangladesh. Grass root level workers play a major role in upgrading RHSB in women. Many factors limit rural access to mother and child health services including distance of the health facility and cost of the health service., Conclusions: In particular, education level, women's autonomy in family decision making and distance from health service can be considered as factors influencing RHSBs in Bangladesh. Exposure to mass media and TV watching are likely to positively impact RHSB patterns for women in Bangladesh., (© 2024 International Federation of Gynecology and Obstetrics.)

The government of Bangladesh has initiated Adolescent Friendly Health Services (AFHS) at health facilities to improve access of adolescents to quality health care. This study aimed to document the AFHS program experiences and interventions implemented in four districts of Bangladesh. The study adopted review of literature, relevant project documents, research reports and analysis of secondary data on AFHS. The secondary data was extracted from the government District Health Information System (DHIS-2) and the HMIS (Health Management Information System) of Family planning department of the four study districts in Bangladesh from 2017 to 2019. Introduction of the AFHS program in Government health facilities had a positive impact on raising awareness among the community. It increased the proportion of adolescents receiving health services (from 6% in the pre-intervention period to 86% in the post-intervention period). The involvement of school authorities in disseminating AFHS program activities resulted in a 68.51% rise in adolescent referrals from schools. Publicity of the program and privacy of the service recipients are considered as enabling factors for the acceptance of AFHS. However, training of the service providers on comprehensive adolescent healthcare packages and expanding logistics support to the health facilities are needed for improvement of the overall service. The government of Bangladesh is committed to implementing adolescent friendly services, evident by adoption of national level strategy and guidelines through government health system, using existing resources with an additional financial support from development partners. The IEC (Information, Education and Communication) materials on AFHS, developed by different organizations were used for awareness program on AFHS. The healthcare providers were oriented/trained on AFHS, mental health, nutrition and counseling skills. Multi-sectoral collaboration at all levels: national to local level (schools, communities, adolescents club) were adopted for sustainability of this initiative., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We evaluated Klebsiella pneumoniae (Kp) gut carriage in healthy, unrelated adults and children living in separate households in Dhaka, Bangladesh. Average Kp prevalence in stool samples ranged from 61% in young children (15/25) to 81% in adults (21/26), with significantly higher abundance in adults ( P = .03, t -test). Kp was also prevalent in household water (64%, 21/33) and standing water (85%, 23/27). The presence of Kp in household water was not strongly linked to stool Kp abundance among household members. Antimicrobial resistance was notable: 9% (6/69) of stool and 16% (7/44) of water isolates exhibited multidrug resistance. Carbapenem resistance was observed in 12% of stool isolates (8/69) and 14% of water isolates (6/44). These findings underscore the commonality of Kp in human and environmental reservoirs in Dhaka, Bangladesh, and highlight the emergence of drug-resistant Kp beyond healthcare settings., Competing Interests: Potential Conflict of interest. J.B.H. and R.C.L. have received royalties from UpToDate. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show that vertebrate centromeres are partitioned by condensins into two subdomains during mitosis. The bipartite structure is found in human, mouse, and chicken cells and is therefore a fundamental feature of vertebrate centromeres. Super-resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores, with each subdomain binding a distinct microtubule bundle. Cohesin links the centromere subdomains, limiting their separation in response to spindle forces and avoiding merotelic kinetochore-spindle attachments. Lagging chromosomes during cancer cell divisions frequently have merotelic attachments in which the centromere subdomains are separated and bioriented. Our work reveals a fundamental aspect of vertebrate centromere biology with implications for understanding the mechanisms that guarantee faithful chromosome segregation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Body coveralls, often made of single-use plastics, are essential Personal Protective Equipment (PPE) and, along with masks, are widely used in healthcare facilities and public spaces in the wake of the recent COVID-19 pandemic. The widespread use of these body coveralls poses a significant threat to terrestrial and aquatic ecosystems, given their polluting nature and disposal frequency. Therefore, it is necessary to promote the adoption of alternatives that increase the safe reusability of PPE clothing and reduce environmental and health hazards. This study presents a comparative Cradle-to-Grave Life Cycle Assessment (LCA) of disposable and reusable PPE body coveralls from a product life cycle perspective. A comprehensive life cycle inventory and LCA framework specific to Indian conditions have been developed through this study. The LCA is performed as per standard protocols using SimaPro software under recipe 2016 (H) impact assessment method. Six midpoint impact categories viz . Global Warming Potential, Terrestrial Acidification, Freshwater Eutrophication, Terrestrial Ecotoxicity, Human Carcinogenic Toxicity, and Water Consumption are assessed, along with Cumulative Energy Demand. Results suggest that reusable PPE improves environmental and human health performance in all the impact categories except water consumption. Sensitivity analysis reveals that replacing conventional electricity with solar energy for PPE manufacturing and disposal will provide additional environmental benefits. The findings can help the medical textile industries, healthcare workers, and policymakers to make environmentally informed choices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier Ltd. All rights reserved.)

The study aimed to evaluate follicular dynamics and concentrations of estradiol-17β (E2), progesterone (P4), follicle stimulating hormone (FSH) and luteinizing hormone (LH) during the oestrous cycle and to determine ovulation time in Mithun cows. Ovaries of experimental cows (n = 7) were examined daily by transrectal-ultrasonography for three consecutive oestrous cycles (n = 21). The characteristics of follicular waves, dominant follicle, largest subordinate follicle and corpus luteum and ovulation time were evaluated. The plasma samples were analysed throughout the interovulatory interval to determine the differences in the hormonal profiles (E2, P4, FSH and LH) between different follicular wave cycles. Out of eighteen oestrous cycles analysed, three-wave follicular cycles were maximum (n = 12: 66.66%) followed by two (n = 4: 22.22%) and four waves (n = 2: 11.11%). The two and three waves were statistically compared, and no significant (p > .05) differences were observed in day of wave emergence, number of follicles (≥3 mm) recruited, maximum diameter of the ovulatory dominant follicle, growth rates of ovulatory and anovulatory dominant follicles and maximum diameter of corpus luteum. The diameter of dominant follicles was significantly (p < .05) greater than subordinate follicles in both ovulatory and anovulatory waves. No significant differences were observed in peak concentrations of estradiol-17β and follicle stimulating hormone between ovulatory and anovulatory waves in all wave cycles. A preovulatory luteinizing hormone surge was observed a day before ovulation in all wave cycles. Progesterone concentrations were lower than 0.5 ng/ml during oestrus and increased sharply to the maximum levels of ≥3.8 ng/ml in all wave cycles. Ovulation time (mean ± SEM), irrespective of follicular waves was 10.5 ± 0.64 h after the end of oestrus. It was concluded that Mithun cows have a preponderance of three follicular waves with little difference between the two- and three-follicular waves and ovulation occurred 10.5 h after the end of oestrus., (© 2022 Wiley-VCH GmbH.)

Clean energy transition via utilizing biomass resources has been projected as an important climate change mitigation strategy. A vital characteristic of biomass is its localized nature; therefore, bioenergy utilization should follow decentralized planning. Agrarian countries like India can take benefit of its large agricultural biomass waste pool to produce clean renewable energy. However, prior knowledge of spatio-temporal distribution, competing uses, and biomass characteristics are necessary for successful bioenergy planning. This paper assesses biomass resource and its power generation potential at different agro-climatic zone levels in the state of Rajasthan, India considering crop residue biomass (25 different crop residues from 14 crops) and livestock manure (from cattle, buffalo, and poultry). Uncertainties associated with the availability of biomass and the power generation potential are assessed for each agro-climatic zone under different scenarios. Greenhouse gases (GHGs) emissions from biomass-based power generations are also estimated and compared with biomass-equivalent coal power plants. It is observed that the annual biomass power potential of Rajasthan is 3056 MW (2496 MW from crop residues and 560 MW from livestock manure). Scenario analysis suggests that the potential varies from 2445 to 6045 MW under different biomass availability and power plant operating conditions. Annual GHGs emissions due to biomass power generation is 5053 kt CO 2 eq. Replacing coal-based power with biomass power would result in annual GHGs savings of 11412 kt CO 2 eq. The paper also discusses various carriers and barriers viz. logistics, institutional, financial and technical in setting up decentralized bioenergy plants. Outcomes of the present study are expected to assist renewable energy planners in India., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Osteoblast differentiation is critically reduced in various bone-related pathogenesis, including arthritis and osteoporosis. For future development of effective regenerative therapeutics, herein, we reveal the involved molecular mechanisms of a phytoestrogen, ferutinin-induced initiation of osteoblast differentiation from dental pulp-derived stem cell (DPSC). We demonstrate the significantly increased expression level of a transcription factor, Kruppel-like factor 2 (KLF2) along with autophagy-related molecules in DPSCs after induction with ferutinin. The loss-of-function and the gain-of-function approaches of KLF2 confirmed that the ferutinin-induced KLF2 modulated autophagic and OB differentiation-related molecules. Further, knockdown of the autophagic molecule (ATG7 or BECN1) from DPSC resulted not only in a decreased level of KLF2 but also in the reduced levels of OB differentiation-related molecules. Moreover, mitochondrial membrane potential-related molecules were increased and induction of mitophagy was observed in DPSCs after the addition of ferutinin. The reduction of mitochondrial as well as total ROS generations; and induction of intracellular Ca 2+ production were also observed in ferutinin-treated DPSCs. To test the mitochondrial respiration in DPSCs, we found that the cells treated with ferutinin showed a reduced extracellular acidification rate (ECAR) than that of their vehicle-treated counterparts. Furthermore, mechanistically, chromatin immunoprecipitation (ChIP) analysis revealed that the addition of ferutinin in DPSCs not only induced the level of KLF2, but also induced the transcriptionally active epigenetic marks (H3K27Ac and H3K4me3) on the promoter region of the autophagic molecule ATG7. These results provide strong evidence that ferutinin stimulates OB differentiation via induction of KLF2-mediated autophagy/mitophagy., (© 2022. The Author(s).)

The study aimed to describe a comparative ejaculatory response, fresh and frozen-thawed semen quality and fertility of semen collected by artificial vagina and electroejaculation in mithun. Experimental bulls were divided into two groups, G-I: young bulls (n = 4; 4-5 years of age) and G-II: older bulls (n = 4; 8-10 years of age). Sixteen ejaculates were collected from each group G-I (AV 1 ) and G-II (AV 2 ) by artificial vagina method (control). Thirty-six ejaculates were collected from the same bulls from each group G-I (EE 1 ) and G-II (EE 2 ) by electroejaculation method (treatment). The study did not reveal any significant (p > 0.05) difference in the ejaculatory responses between EE 1 and EE 2 . Mann-Whitney U test indicated that salivation discomfort sign score was significantly (p < 0.05) higher in EE 1 . Fresh and frozen-thawed semen quality parameters, and motility and velocity profiles recorded by computer-assisted sperm analyser were significantly (p < 0.05) lower in electroejaculation than the artificial vagina. The conception rates (AV 1 vs EE 1 & AV 2 vs EE 2 ) at day 35-45 post insemination were nonsignificantly higher (p > 0.05) in the artificial vagina group. It concluded that, although artificial vagina method has better semen quality, nevertheless, electroejaculation has the potential for semen collection from free-range mithun bulls to incorporate in assisted reproductive technology procedures., (© 2021 Wiley-VCH GmbH.)

Ethnopharmacological Relevance: Dengue virus (DENV) is a re-emerging mosquito-borne flavivirus that has recently engendered large epidemics around the world. Consequently antivirals with effective anti-DENV therapeutic activity are urgently required. In the 18th century, Europeans, as well as native inhabitants of North America, were known to adapt the medicinal property of the common perennial plant Eupatorium perfoliatum L. to treat fever and infections. Previous studies have shown that Eupatorium perfoliatum L. possesses anti-inflammatory, anti-oxidative, anti-plasmodial, anti-bacterial and antiviral activities. However, to the best of our knowledge, no anti-DENV activity of E. perfoliatum L. has been investigated at the molecular level so far., Aim of Study: Here, for the first time we have attempted to study the action of E. perfoliatum extract and its few bioactive components i.e., quercetin, caffeic acid and eupafolin against wild primary clinical isolate of DENV-2 infection in an in vitro model., Materials and Methods: The presence of the bioactive components in the E. perfoliatum extract, were analyzed by HPLC- DAD. Then, CC 50 as well as IC 50 values of the extract and its bioactive components were measured against DENV in HepG2 cell line. After that, the antiviral activity was studied by Time of addition assay using qRT-PCR. Further, the downstream signalling action of E. perfoliatum extract, was studied by Human phosphorylation MAPK antibody array, followed by immunofluorescence microscopy. Moreover, a molecular docking analysis was done to study the binding affinity of bioactive components of E. perfoliatum extract with TIM-1 transmembrane receptor protein, which is known for viral internalization., Result: We found that E. perfoliatum extract has marked antiviral activity during pre-treatment against DENV infection in HepG2 cell line. The extract also significantly reduced the DENV induced autophagy in HepG2 cell line as detected by LC3 II localization. The presence of different bioactive compounds in E. perfoliatum extract were confirmed by HPLC-DAD. In the bioactive components, in parallel to earlier studies, quercetin showed the most significant preventive action against DENV infection. Further, in molecular docking analysis also, quercetin showed the strongest binding affinity towards DENV membrane receptor TIM-1 protein., Conclusion: Our findings suggests that E. perfoliatum extract has significant potential to be an anti-DENV therapeutic agent. Moreover, among the bioactive components, quercetin may have a prophylaxis role in executing the antiviral activity of E. perfoliatum extract against DENV infection., (Copyright © 2021. Published by Elsevier B.V.)

To define the role of SETD2 in the WNT5a signaling in the context of osteoclastogenesis, we exploited two different models: in vitro osteoclast differentiation, and K/BxN serum-induced arthritis model. We found that SETD2 and WNT5a were upregulated during osteoclast differentiation and after induction of arthritis. Using gain- and loss-of-function approaches in the myeloid cell, we confirmed that SETD2 regulated the osteoclast markers, and WNT5a via modulating active histone marks by enriching H3K36me3, and by reducing repressive H3K27me3 mark. Additionally, during osteoclastic differentiation, the transcription of Wnt5a was also associated with the active histone H3K9 and H4K8 acetylations. Mechanistically, SETD2 directed induction of NF-κβ expression facilitated the recruitment of H3K9Ac and H4K8Ac around the TSS region of the Wnt5a gene, thereby, assisting osteoclast differentiation. Together these findings for the first time revealed that SETD2 mediated epigenetic regulation of Wnt5a plays a critical role in osteoclastogenesis and induced arthritis. Model for the Role of SETD2 dependent regulation of osteoclastic differentiation. A In monocyte cells SETD2-dependent H3K36 trimethylation help to create open chromatin region along with active enhancer mark, H3K27Ac. This chromatin state facilitated the loss of a suppressive H3K27me3 mark. B Additionally, SETD2 mediated induction of NF-κβ expression leads to the recruitment of histone acetyl transferases, P300/PCAF, to the Wnt5a gene and establish H3K9Ac and H4K8Ac marks. Along with other activation marks, these acetylation marks help in Wnt5a transcription which leads to osteoclastogenesis., (© 2021. The Author(s).)

MicroRNAs (miRNAs) are key epigenomic regulators of biological processes in animals and plants. These small non coding RNAs form a complex networks that regulate cellular function and development. MiRNAs prevent translation by either inactivation or inducing degradation of mRNA, a major concern in post-transcriptional gene regulation. Aberrant regulation of gene expression by miRNAs is frequently observed in cancer. Overexpression of various 'oncomiRs' and silencing of tumor suppressor miRNAs are associated with various types of human cancers, although overall downregulation of miRNA expression is reported as a hallmark of cancer. Modulations of the total pool of cellular miRNA by alteration in genetic and epigenetic factors associated with the biogenesis of miRNA machinery. It also depends on the availability of cellular miRNAs from its store in the organelles which affect tumor development and cancer progression. Here, we have dissected the roles and pathways of various miRNAs during normal cellular and molecular functions as well as during breast cancer progression. Recent research works and prevailing views implicate that there are two major types of miRNAs; (i) intracellular miRNAs and (ii) extracellular miRNAs. Concept, that the functions of intracellular miRNAs are driven by cellular organelles in mammalian cells. Extracellular miRNAs function in cell-cell communication in extracellular spaces and distance cells through circulation. A detailed understanding of organelle driven miRNA function and the precise role of extracellular miRNAs, pre- and post-therapeutic implications of miRNAs in this scenario would open several avenues for further understanding of miRNA function and can be better exploited for the treatment of breast cancers., (Copyright © 2020. Published by Elsevier Ltd.)

Sugarcane is an important cash crop used for producing sweeteners and also some bioproducts (alcohol and bioenergy). The current study assesses life cycle energy, carbon and water footprint of sugarcane based sugar, ethanol and electricity in India. A farm to factory gate attributional life cycle assessment (LCA) is conducted to assess the energy and carbon footprints whereas the Food and Agriculture Organization's (FAO) CropWat model is used to estimate the water footprint (green, blue and grey). For the base case, electricity has the highest energy return on investment (EROI), lowest carbon and water footprints among the bioproducts. The choice of allocation method (economic, mass, and energy) impacts the energy and environmental outcomes of the bioproducts. The comparison among four different sugarcane seasons shows that bioproducts available from Adsali sugarcane have the highest EROI, lowest carbon and water footprints. The findings could lead to improved sustainability of sugarcane bioproducts in India., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To define the regulatory role of Kruppel-like factor 2 (KLF2) during osteoblast (OB) differentiation of dental pulp-derived stem cell (DPSC)s, herein, we show that the levels of KLF2 and autophagy-related molecules were significantly increased in differentiated cells. Gain-of-function and loss-of-function approaches of KLF2 confirmed that KLF2 modulated autophagic and OB differentiation-related molecules. In addition, knockdown of the autophagic molecule (ATG7 or BECN1) in DPSCs resulted in reduced levels of KLF2 and OB differentiation-related molecules. Conversely, the induction of autophagy increased levels of KLF2 and OB differentiation-related molecules. Moreover, OB differentiation induced mitophagy and mitochondrial membrane potential-related molecules. In addition, OB differentiation reduced the generation of total and mitochondrial ROS productions and induced intracellular Ca 2+ production. Measurements of glycolysis and oxidative phosphorylation simultaneously in live cells revealed that OB differentiation decreased the oxygen consumption rate, which is an indicator of mitochondrial respiration and reduced the level of ATP production. Furthermore, flux analysis also revealed that OB differentiation increased the extracellular acidification rate (ECAR) in the non-glycolytic acidification, and the glycolytic capacity conditions, increasing the lactate production and reducing the metabolic activity of the cells. Thus, a metabolic shift from mitochondrial respiration to the glycolytic pathway was observed during OB differentiation. Finally, chromatin immunoprecipitation (ChIP) analysis confirmed that the KLF2 and active epigenetic marks (H3K27Ac and H3K4me3) were upregulated in the promoter region of ATG7 during OB differentiation. These results provide evidence that the mitophagy process is important during OB differentiation, and KLF2 critically regulates it., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bioelectrochemical systems like microbial fuel cells (MFCs) are quaint systems known to metamorphose the chemical energy of organic matter into electrical energy using catalytic activity of microorganisms. A novel continuous Auto Circulating Bio-Electrochemical Reactor (AutoCirBER) was developed to fulfil the gap of 'simple, inexpensive and compact design' that can continuously treat larger amount of organic wastewater at shorter residence time and without consuming external energy for liquid mixing. AutoCirBER eliminated the need for external agitation for liquid-mixing and therefore, energy requirements. AutoCirBER was operated in continuous-mode and hydraulic retention time was optimized. The reactor underwent performance check-up viz. COD removal, net power output, columbic efficiency, sludge generation and an attributional life cycle assessment (LCA) was also conducted. AutoCirBER was sustainable to run in continuous-mode and showed more than 90.4% of COD removal, and 59.55 W.h net annual energy recovery. Experimental LCA of AutoCirBER also displays its environmental feasibility in longer run., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Osteoporosis is a silent systemic disease that causes bone deterioration, and affects over 10 million people in the US alone. This study was undertaken to develop a potential stem cell therapy for osteoporosis. We have isolated and expanded human dental pulp-derived stem cells (DPSCs), characterized them, and confirmed their multipotential differentiation abilities. Stem cells often remain quiescent and require activation to differentiate and function. Herein, we show that ferutinin activates DPSCs by modulating the Wnt/β-catenin signaling pathway and key osteoblast-secreted proteins osteocalcin and collagen 1A1 both mRNA and protein levels. To confirm that ferutinin modulates the Wnt pathway, we inhibited glycogen synthase kinase 3 (GSK3) and found that protein expression patterns were similar to those found in ferutinin-treated DPSCs. To evaluate the role of ferutinin in epigenetic regulation of canonical Wnt signaling, the pathway molecules Wnt3a and Dvl3 were analyzed using chromatin immunoprecipitation (ChIP)-quantitative PCR approaches. We confirmed that active marks of both H3K9 acetylation and H3K4 trimethylation were significantly enhanced in the promoter sites of the WNT3A and DVL3 genes in DPSCs after addition of ferutinin. These data provide evidence that ferutinin activates and promotes osteogenic differentiation of DPSCs, and could be used as an inducer as a potentially effective stem cell therapy for osteoporosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Globally, livestock is an important contributor to methane (CH 4 ) emissions. This paper reviewed the various CH 4 measurement and estimation techniques and mitigation approaches for the livestock sector. Two approaches for enteric livestock CH 4 emission estimation are the top-down and bottom-up. The combination of both could further improve our understanding of enteric CH 4 emission and possible mitigation measures. We discuss three mitigation approaches: reducing emissions, avoiding emissions, and enhancing the removal of emissions from livestock. Dietary management, livestock management, and breeding management are viable reducing emissions pathways. Dietary manipulation is easily applicable and can bring an immediate response. Economic incentive policies can help the livestock farmers to opt for diet, breeding, and livestock management mitigation approaches. Carbon pricing creates a better option to achieve reduction targets in a given period. A combination of carbon pricing, feeding management, breeding management, and livestock management is more feasible and sustainable CH 4 emissions mitigation strategy rather than a single approach., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A massive bovine, Bos frontalis, also known as Mithun or Gayal, found at higher altitude is very promising meat and milk animal. For candidate gene and marker discovery, RNA-seq data was generated from longissimus dorsi muscle tissues with Illumina-HiSeq. Such markers can be used in future for genetic gain of traits like feed conversion efficiency (FCE) and average daily gain (ADG). Analysis revealed 297differentially expressed genes (DEGs) having 173 up and 124 down-regulated unigenes. Extensive conservation was found in genic region while comparing with Bos taurus. Analysis revealed 57 pathways having 112 enzymes, 72 transcriptional factors and cofactors, 212 miRNAs regulating 71 DEGs, 25,855 SSRs, mithun-specific 104,822 variants and 7288 indels, gene regulatory network (GRN) having 24 hub-genes and transcriptional factors regulating cell proliferation, immune tolerance and myogenesis. This is first report of muscle transcriptome depicting candidate genes with GRN controlling FCE and ADG. Reported putative molecular markers, candidate genes and hub proteins can be valuable genomic resources for association studies in genetic improvement programme., (Copyright © 2019. Published by Elsevier Inc.)

Macroautophagy/autophagy is involved in myeloid cellular repair, destruction, and osteoclast differentiation; conversely, KLF2 (kruppel-like factor 2 [lung]) regulates myeloid cell activation and differentiation. To investigate the specific role of KLF2 in autophagy, osteoclastic differentiation was induced in monocytes in presence or absence of the autophagy inhibitor 3-methyladenine (3-MA), KLF2 inducer geranylgeranyl transferase inhibitor (GGTI298), and adenoviral overexpression of KLF2. We found that the number of autophagic cells and multinucleated osteoclasts were significantly decreased in presence of 3-MA, GGTI298, and KLF2 overexpressed cells indicating involvement of KLF2 in these processes. In addition, autophagy-related protein molecules were significantly decreased after induction of KLF2 during the course of osteoclastic differentiation. Furthermore, induction of arthritis in mice reduced the level of Klf2 in monocytes, and enhanced autophagy during osteoclastic differentiation. Mechanistically, knocking down of KLF2 increased the level of Beclin1 (BECN1) expression, and conversely, KLF2 over-expression reduced the level of BECN1 in monocytes. Moreover, 3-MA and GGTI298 both reduced myeloid cell proliferation concomitantly upregulating senescence-related molecules (CDKN1A/p21 and CDKN1B/p27 kip1 ). We further confirmed epigenetic regulation of Becn1 by modulating Klf2 ; knocking down of Klf2 increased the levels of histone activation marks H3K9 and H4K8 acetylation in the promoter region of Becn1 ; and overexpression of Klf2 decreased the levels of H4K8 and H3K9 acetylation. In addition, osteoclastic differentiation also increased levels of H3K9 and H4K8 acetylation in the promoter region of Becn1 . Together these findings for the first time revealed that Klf2 critically regulates Becn1 -mediated autophagy process during osteoclastogenesis. Abbreviations : ACP5/TRAP: acid phosphatase 5, tartrate resistant; Ad-KLF2: adenoviral construct of KLF2; ATG3: autophagy related 3; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; BECN1: beclin 1, autophagy related; C57BL/6: inbred mouse strain C57 black 6; ChIP: chromatin immunoprecipitation; CSF1/MCSF: colony stimulating factor 1 (macrophage); CTSK: cathepsin K; EV: empty vector; GGTI298: geranylgeranyl transferase inhibitor; H3K9Ac: histone H3 lysine 9 acetylation; H4K8Ac: histone H4 lysine 8 acetylation; K/BxN mice: T cell receptor (TCR) transgene KRN and the MHC class II molecule A(g7) generates K/BxN mice; KLF2: kruppel-like factor 2 (lung); 3MA: 3-methyladenine; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MDC: monodansylcadaverine; NFATc1: nuclear factor of activated T cells 1; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; p21/CDKN1A: cyclin dependent kinase inhibitor 1A; p27 kip1 /CDKN1B: cyclin-dependent kinase inhibitor 1B; PCR: polymerase chain reaction; PtdIns3K: phosphoinositide 3-kinase; RA: rheumatoid arthritis; si Klf2 : small interfering KLF2 ribonucleic acid; NS: non-specific; RAW 264.7: abelson murine leukemia virus transformed macrophage cell line; TNFSF11/RANKL: tumor necrosis factor (ligand) superfamily, member 11; TSS: transcriptional start site; UCSC: University of California, Santa Cruz.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis.

Aberrant epigenetic modifications are responsible for tumor development and cancer progression; however, readily reversible. Bioactive molecules from diets are promising to cure cancer by modulating epigenetic marks and changing immune response. These compounds specifically target the activity of DNMTs and HDACs to cure various human cancers. In view of this, we investigated the anticancer and epigenetic regulatory activities of an edible-plant Paederia foetida. The efficacy of methanolic extract of P. foetida leaves (MEPL) was tested for the modulation of epigenetic factors in gene silencing, i.e. DNMT and HDAC and expression pattern of certain tumor-suppressor genes. After treatment of prostate cancer cells (PC-3 and DU-145) with MEPL, lupeol and β-sitosterol; induction of apoptosis, decrease in cellular-viability and inhibition of cellular-migration were noticed. Simultaneously there was inhibition of DNMT1, HDACs and pro-inflammatory, IL-6, IL1-β, TNF-α and anti-inflammatory, IL-10 genes in cancer and THP1 cell lines. The DNMT1 protein content, enzyme activity and Bcl2 expression decreased significantly; however, expression of E-cadherin (CDH1) and pro-apoptotic gene Bax increased significantly after the treatment of cells with drugs. We conclude plant-derived compounds can be considered to target epigenetic machineries involved with malignant transformation and can open new avenues for cancer therapeutics provoking immune response., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Mixed-lineage leukaemia 1 (MLL1) enzyme plays major role in regulating genes associated with vertebrate development. Cell physiology and homeostasis is regulated by microRNAs in diverse microenvironment. In this investigation we have identified conserved miR-193a target sites within the 3'-UTR of MLL1 gene transcript. Utilizing wild type and mutated 3'-UTR constructs and luciferase reporter assays we have clearly demonstrated that miR-193a directly targets the 3'-UTR region of the MLL1 mRNA. Ectopic expression of miR-193a modulated global H3K4 mono-, di- and tri-methylation levels and affects the expression of CAV1, a gene which is specifically modulated by H3K4me3. To determine the implications of this in vitro finding in aberrant physiological conditions we analyzed prostate cancer tissue samples. In this context miR-193a RNA was undetectable and MLL1 was highly expressed with concomitantly high levels of H3K4me, H3K4me2, and H3K4me3 enrichment in the promoters of MLL1 responsive genes. Finally, we showed that prolonged ectopic expression of miR-193a inhibits growth and cell migration, and induces apoptosis. Thus, while our study unveils amplitude of the epigenome, including miRnome it establishes that; (i) miR-193a directly target MLL1 mRNA, (ii) miR-193a impair MLL1 protein production, (iii) miR-193a reduces the overall methylation marks of the genome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Loss of E-cadherin and epithelial to mesenchymal transition (EMT) are key steps in cancer progression. Reactive oxygen species (ROS) play significant roles in cellular physiology and homeostasis. Roles of E-cadherin (CDH1), EMT and ROS are intriguingly illustrated in many cancers without focusing their collective concert during cancer progression. We report that hydrogen peroxide (H 2 O 2 ) treatment modulate CDH1 gene expression by epigenetic modification(s). Sublethal dosage of H 2 O 2 treatment decrease E-cadherin, increase DNMT1, HDAC1, Snail, Slug and enrich H3K9me3 and H3K27me3 in the CDH1 promoter. The effect of H 2 O 2 was attenuated by ROS scavengers; NAC, lupeol and beta-sitosterol. DNMT inhibitor, AZA prevented the H 2 O 2 induced promoter-CpG-island methylation of CDH1. Treatment of cells with U0126 (inhibitor of ERK) reduced the expression of DNMT1, Snail and Slug, increased CDH1. This implicates that CDH1 is synergistically repressed by histone methylation, DNA methylation and histone deacetylation mediated chromatin remodelling and activation of Snail and Slug through ERK pathway. Increased ROS leads to activation of epigenetic machineries and EMT activators Snail/Slug which in their course of action inactivates CDH1 gene and lack of E-cadherin protein promotes EMT in breast cancer cells. ROS and ERK signaling facilitate epigenetic silencing and support the fact that subtle increase of ROS above basal level act as key cell signaling molecules. Free radical scavengers, lupeol and beta-sitosterol may be tested for therapeutic intervention of breast cancer. This work broadens the amplitude of epigenome and open avenues for investigations on conjoint effects of canonical and intrinsic metabolite signaling and epigenetic modulations in cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Microtubule associated tumor suppressor 1 (MTUS1) has been recognized as a tumor suppressor gene in multiple cancers. However, the molecular mechanisms underlying the regulation of MTUS1 are yet to be investigated. This study aimed to clarify the significance of DNA methylation in silencing MTUS1 expression. We report that MTUS1 acts as tumor suppressor in non-small cell lung carcinoma (NSCLC). Analysis of in silico database and subsequent knockdown of DNMT1 suggested an inverse correlation between DNMT1 and MTUS1 function. Interestingly, increased methylation at MTUS1 promoter is associated with low expression of MTUS1. Treatment with DNA methyltransferases (DNMTs) inhibitor, 5-aza-2'-deoxycytidine (AZA) leads to both reduced promoter methylation accompanied with enrichment of H3K9Ac and enhanced MTUS1 expression. Remarkably, knockdown of MTUS1 showed increased proliferation and migration of NSCLC cells in contrast to diminished proliferation and migration, upon treatment with AZA. We concluded that low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The current study aimed at genomic characterization and improved understanding of genetic diversity of two Indian mithun populations (both farm, 48 animals and field, 24 animals) using genome wide genotype data generated with Illumina BovineHD BeadChip. Eight additional populations of taurine cattle (Holstein and NDama), indicine cattle (Gir) and other evolutionarily closely related species (Bali cattle, Yak, Bison, Gaur and wild buffalo) were also included in this analysis (N = 137) for comparative purposes. Our results show that the genetic background of mithun populations was uniform with few possible signs of indicine admixture. In general, observed and expected heterozygosities were quite similar in these two populations. We also observed increased frequencies of small-sized runs of homozygosity (ROH) in the farm population compared to field mithuns. On the other hand, longer ROH were more frequent in field mithuns, which suggests recent founder effects and subsequent genetic drift due to close breeding in farmer herds. This represents the first study providing genetic evidence about the population structure and genomic diversity of Indian mithun. The information generated will be utilized for devising suitable breeding and conservation programme for mithun, an endangered bovine species in India.

Functional analyses of noncoding RNAs have associated many micro RNAs (miRNA, miR) with various physiological processes, including proliferation, differentiation, development, cell metabolism, and apoptosis. Aberrant expression of miRNA and imbalance in their functions may lead to cellular aberration and different disease development, including cancer. In silico analysis of miRNA target prediction suggested that miR-148a possess a binding site in the 3' UTR of DNMT1 mRNA which can cause silencing of DNMT1 gene. Accordingly, we performed in vitro cell culture experiments to confirm the effect miR-148a on DNMT1 gene expression in prostate cancer cell lines. We demonstrated that there is a physical association between DNMT1 mRNA and miR-148a. We found that (i) ectopic expression of miR-148a induces programmed cell death and represses cell proliferation by targeting DNMT1; (ii) miR-148a gene is regulated by DNA methylation and DNMT1 in prostate cancer. We conclude that miR-148a is silenced by DNA methylation and ectopic expression of miR-148a suppresses DNMT1 expression and induced apoptotic genes expression in hormone-refractory prostate cancer cells., (Copyright © 2018. Published by Elsevier B.V.)

Two climate metrics, Global surface Temperature Change Potential (GTP) and the Absolute GTP (AGTP) are used for studying the global surface temperature impact of CH 4 emission from livestock in India. The impact on global surface temperature is estimated for 20 and 100 year time frames due to CH 4 emission. The results show that the CH 4 emission from livestock, worked out to 15.3 Tg in 2012. In terms of climate metrics GTP of livestock-related CH 4 emission in India in 2012 were 1030 Tg CO 2 e (GTP 20 ) and 62 Tg CO 2 e (GTP 100 ) at the 20 and 100 year time horizon, respectively. The study also illustrates that livestock-related CH 4 emissions in India can cause a surface temperature increase of up to 0.7mK and 0.036mK over the 20 and 100 year time periods, respectively. The surface temperature response to a year of Indian livestock emission peaks at 0.9mK in the year 2021 (9 years after the time of emission). The AGTP gives important information in terms of temperature change due to annual CH 4 emissions, which is useful when comparing policies that address multiple gases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pangong is a brackish water lake having environmental conditions that are hostile to supporting life. This is the first report unveiling the microbial diversity of sediment from Pangong Lake, Ladakh, India, using a high-throughput metagenomic approach. Metagenomic data analysis revealed a community structure of microbes in which functional genetic diversity facilitates their survival., (Copyright © 2017 Rathour et al.)

Sustainability of a bioenergy project depends on precise assessment of biomass resource, planning of cost-effective logistics and evaluation of possible environmental implications. In this context, this paper reviews the role and applications of geo-spatial tool such as Geographical Information System (GIS) for precise agro-residue resource assessment, biomass logistic and power plant design. Further, application of Life Cycle Assessment (LCA) in understanding the potential impact of agro-residue bioenergy generation on different ecosystem services has also been reviewed and limitations associated with LCA variability and uncertainty were discussed. Usefulness of integration of GIS into LCA (i.e. spatial LCA) to overcome the limitations of conventional LCA and to produce a holistic evaluation of the environmental benefits and concerns of bioenergy is also reviewed. Application of GIS, LCA and spatial LCA can help alleviate the challenges faced by ambitious bioenergy projects by addressing both economics and environmental goals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Phospholipase C (PLC) 1 is known to help the pathogen B. cereus entry to the host cell and human PLC is over expressed in multiple cancers. Knowledge of dynamic activity of the enzyme PLC while in action on membrane lipids is essential and helpful to drug design and delivery. In view of this, interactions of PLC with liposome of various lipid compositions have been visualized by testing enzyme activity and microenvironments around the intrinsic fluorophores of the enzyme. Overall change of the protein's conformation has been monitored by fluorescence spectroscopy and circular dichroism (CD). Liposome aggregation and fusion were predicted by increase in turbidity and vesicle size. PLC in solution has high fluorescence and exhibit appreciable shift in its emission maxima, upon gradual change in excitation wavelength towards the red edge of the absorption band. REES fluorescence studies indicated that certain Trp fluorophores of inactive PLC are in motionally restricted compact/rigid environments in solution conformation. PLC fluorescence decreased in association with liposome and Trps loosed rigidity where liposome aggregation and fusion occurred. We argue that the structural flexibility is the cause of decrease of fluorescence, mostly to gain optimum conformation for maximum activity of the enzyme PLC. Further studies deciphered that the enzyme PLC undergoes change of conformation when mixed to LUVs prepared with specific lipids. CD data at the far-UV and near-UV regions of PLC in solution are in excellent agreement with the previous reports. CD analyses of PLC with LUVs, showed significant reduction of α-helices, increase of β-sheets; and confirmed dramatic change of orientations of Trps. In case of liposome composed of lipid raft like composition, the enzyme binds very fast, hydrolyze PC with higher rate, exhibit highest structural flexibility and promote vesicle fusion. These data strongly suggest marked differences in conformation transition induced PLC activation and liposome fusion on the lipid composition., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Developmentally inclined hedgehog (HH) signaling pathway and pluripotency inducing transcription factor SOX2 have been known to work syngerstically during cellular reprogramming events to facilitate efficient differentiation. Hence, it is not surprising that both the factors are actively involved in arbitrating malignant growth, including prostate cancer progression. Here, we have described in details the potential mechanisms by which SOX2 effects neoplastic characteristics in prostate cancer and investigated the consequences of simultaneous down-regulation of SOX2 and HH pathway in androgen-independent human prostate cancer cells. Expression of SOX2 has been determined by qRT-PCR, western blot, immunohistochemistry and immunocytochemistry analyses; its functional role determined by gene knockdown using RNAi and over-expression via chemical activation in HaCaT, DU145 and PC-3 cells. Changes in level of cell proliferation, migration and apoptosis profiles were measured by MTT, FACS, chromatin condensation and scratch assays respectively. SOX2 was expressed in all the three cell lines and its inhibition reduced cell proliferation and induced apoptosis. Most importantly, when both SOX2 and HH pathway were targeted simultaneously, cell proliferation was greatly reduced, apoptotic cell population increased drastically and migration potential was reduced. Moreover, gene expression of EMT markers such as E-cadherin and apoptosis related Bcl-2 and Bax was also investigated wherein decrease in E-cadherin and Bcl-2 levels and increase in Bax expression further substantiating our claim. These findings could provide the basis for a novel therapeutic strategy targeting both the effector i.e. SOX2 and perpetuator i.e. HH pathway of aggressive tumorigenic properties in androgen independent prostate cancer., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 μM. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.

MicroRNAs (miRNA) are small non-coding RNAs which targets most protein-coding transcripts (mRNA) and destroy them. Thus miRNA controls the abundance of those specific proteins and impact on developmental, physiological and pathological processes. Dysregulation of miRNA function thus may lead to various clinicopathological complications, including breast cancer. Silencing of miR-152 gene due to promoter DNA methylation alter the expression pattern of several other genes. E-cadherin (CDH1) forms the core of adherent junctions between surrounding epithelial cells, link with actin cytoskeleton and affects cell signaling. CDH1 gene is down regulated by promoter DNA methylation during cancer progression. In this investigation, we attempt to elucidate the correlation of miR-152 and CDH1 function, as it is well known that the loss of CDH1 function is one of the major reasons for cancer metastasis and aggressiveness of spreading. For the first time we have shown that loss of CDH1 expression is directly proportional to the loss of miR-152 function in breast cancer cells. mRNA and protein expression profile of DNMT1 implicate that miR-152 targets DNMT1 mRNA and inhibits its protein expression. Tracing the molecular marks on DNA and histone 3 for understanding the mechanism of gene regulation by ChIP analyses leads to a paradoxical result that shows DNA methylation adjacent to active histone marking (enrichment of H3K4me3) silence miR-152 gene. Further experiments revealed that DNMT1 plays crucial role for regulation of miR-152 gene. When DNMT1 protein function is blocked miR-152 expression prevails and destroys the mRNA of DNMT1; this molecular regulatory mechanism is creating a cyclic feedback loop, which is now focused as DNMT1/miR-152 switch for on/off of DNMT1 target genes. We discovered modulation of CDH1 gene expression by DNMT1/miR-152 switches. We have demonstrated further that DNMT1 down regulation mediated upregulation of CDH1 (hereafter, DNMT1/CDH1 loop) in presence of ectopic-excess of miR-152 prevents migration of cancer cells. Our data provides novel insights into the regulation mechanism of miRNA and mRNA/protein coding genes and enhances the amplitude of cancer epigenome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Caveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation., Methods: We have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively., Results: Ectopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter., Conclusions: Our data provides novel insight into the regulation of CAV1 gene by histone H3 modifications and enhance the amplitude of the cancer epigenome., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Many HDAC inhibitors have passed through the gateway of clinical trials. However, they have limited therapeutic implications due to their pleiotropic pharmaceutical properties and off-target effects. In view of this, dietary active phytochemicals were evaluated. Based upon the chemical and structural insights of HDAC active pockets, thymoquinone (TQ) was investigated to uncover its active participation in HDAC inhibition. The synergistic analysis of docking and molecular dynamics simulation disclosed the elementary interaction and stability of TQ with human HDACs. The in silico findings were corroborated with an in vitro analysis, demonstrating the efficient role of TQ in the attenuation of global HDAC activity. Furthermore, TQ also elicited downstream effects of HDAC inhibition: reactivation of HDAC target genes (p21 and Maspin), induction of the pro-apoptotic gene Bax, down regulation of the anti-apoptotic gene Bcl-2 and arrest of the cell cycle at the G2/M phase. Finally, the result of a higher cytotoxicity of TQ towards MCF-7 breast cancer cells in comparison to normal cells indicates the potential of TQ to be an anticancer drug.

Clusterin (CLU) is an important glycoprotein involved in various cellular functions. Different reports have mentioned that the two isoforms of CLU; secretary (sCLU) and nuclear (nCLU) have opposite (paradoxical) roles in cancer development. sCLU provides pro-survival signal, whereas nCLU is involved in pro-apoptotic signaling. However, the molecular mechanism of CLU gene regulation is not clear as of yet. We hypothesize that CLU gene is regulated by DNA methylation and histone modifications and clusterin plays an important role in colon cancer. To evaluate the hypothesis, we investigated CLU expression in colon cancer tissues and DNA methylation and histone modification status of CLU gene promoter. It is apparent from immonohistology data that both benign and cancerous (primary and metastasis) formalin fixed paraffin embedded (FFPE) tissue samples exhibit CLU expression. However and interestingly only noncancerous tissue samples show nCLU expression. Ectopic expression of nCLU either by epigenetic modulators or by nCLU transfection is responsible for colon cancer cell death. To clarify the molecular mechanisms for regulation of expression of CLU isoforms, we have analyzed DNA methylation and histone modifications, such as histone H3K9me3, H3K27me3, H3K4me3, and H3K9AcS10P patterns around the CLU promoter. There is no remarkable change in the DNA methylation status upon treatment of the cells by AZA, TSA and SAM. Our findings clearly show that promoter histone H3K9me3 and H3K27me3 marks are elevated in comparison to H3K4me3 and H3K9AcS10P marks in colon cancer cell lines., (Copyright © 2015 Elsevier B.V. All rights reserved.)

DNA methyltransferases (DNMTs) is a key epigenetic enzyme for pharmacological manipulation and is employed in cancer reprogramming. During past few years multiple strategies have been implemented to excavate epigenetic compounds targeting DNMTs. In light of the emerging concept of chemoinformatics, molecular docking and simulation studies have been employed to accelerate the development of DNMT inhibitors. Among the DNMT inhibitors known till date, epigallocathechin-3-gallate (EGCG) was identified to be effective in reducing DNMT activity. However, the broad spectrum of EGCG to other diseases and variable target enzymes offers some limitations. In view of this, 32 EGCG analogues were screened at S-Adnosyl-L-homocysteine (SAH) binding pocket of DNMTs and procyanidin B2-3, 3'-di-O-gallate (procyanidin B2) was obtained as potent inhibitor having medicinally relevant chemical space. Further, in vitro analysis demonstrates the efficiency of procyanidin B2 in attenuating DNMT activity at IC50 of 6.88±0.647 μM and subsequently enhancing the expression of DNMT target genes, E-cadherin, Maspin and BRCA1. Moreover, the toxic property of procyanidin B2 towards triple negative breast cancer cells to normal cells offers platform for pre-clinical trial and an insight to the treatment of cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Caveolin-1 (CAV1) is an integral part of plasma membrane protein playing a vital role in breast cancer initiation and progression. CAV1 acts both as a tumor suppressor as well as an oncogene, and its activity is thus highly dependent on cellular environment. Keeping this fact in mind, the recent work is designed to reveal the role of CAV1 in inhibiting cancer cell progression in presence of epigenetic modulators like 5-aza-2'-deoxycytidine (AZA), trichostatin A (TSA), S-adenosyl methionine (SAM) and sulforaphane (SFN). Forced expression of CAV1 by AZA, TSA, and SFN is correlated to induction of apoptosis and inhibition of cell migration in breast cancer. In breast cancer along with promoter DNA methylation, other epigenetic mechanisms are also involved in CAV1 expression. These observations clearly provide a new scenario regarding the role of CAV1 in cancer and as a possible therapeutic target in breast cancer.

Background: DNA methylation mediates gene silencing primarily by inducing repressive chromatin architecture via a common theme of interaction involving methyl-CpG binding (MBD) proteins, histone modifying enzymes and chromatin remodelling complexes. Hence, targeted inhibition of MBD protein function is now considered a potential therapeutic alternative for thwarting DNA hypermethylation prompted neoplastic progress. We have analyzed the gene and protein expression level of the principal factors responsible for gene silencing, that is, DNMT and MBD proteins in MCF-7 and MDA-MB-231 breast cancer cell lines after treatment with various epigenetic drugs., Results: Our study reveals that the epigenetic modulators affect the expression levels at both transcript and protein levels as well as encourage growth arrest and apoptosis in MCF-7 and MDA-MB-231 cells. AZA, TSA, SFN, and SAM inhibit cell growth in MCF-7 and MDA-MB-231 cell lines in a dose-dependent manner, that is, with increasing concentrations of drugs the cell viability gradually decreases. All the epigenetic modulators promote apoptotic cell death, as is evident form increased chromatin condensation which is a distinct characteristic of apoptotic cells. From FACS analysis, it is also clear that these drugs induce G2-M arrest and apoptosis in breast cancer cells. Further, transcript and protein level expression of MBDs and DNMTs is also affected - after treatment with epigenetic drugs; the level of transcripts/mRNA of MBDs and DNMTs has consistently increased in general. The increase in level of gene expression is substantiated at the protein level also where treated cells show higher expression of DNMT1, DNMT3A, DNMT3B, and MBD proteins in comparison to untreated cells. In case of tissue samples, the expression of different DNMTs is tissue stage-specific. DNMT1 exhibits significantly higher expression in the metastatic stage, whereas, DNMT3A and DNMT3B have higher expression in the primary stage in comparison to the metastatic samples., Conclusion: The epigenetic modulators AZA, TSA, SFN, and SAM may provide opportunities for cancer prevention by regulating the components of epigenetic gene-silencing machinery especially DNMTs and MBDs.

The dynamic nature of chromatin and its myriad modifications play a crucial role in gene regulation (expression and repression) during development, cellular survival, homeostasis, ageing, and apoptosis/death. Histone 3 lysine 4 methylation (H3K4 methylation) catalyzed by H3K4 specific histone methyltransferases is one of the more critical chromatin modifications that is generally associated with gene activation. Additionally, the deposition of H3 variant(s) in conjunction with H3K4 methylation generates an intricately reliable epigenetic regulatory circuit that guides transcriptional activity in normal development and homeostasis. Consequently, alterations in this epigenetic circuit may trigger disease development. The mechanistic relationship between H3 variant deposition and H3K4 methylation during normal development has remained foggy. However, recent investigations in the field of chromatin dynamics in various model organisms, tumors, cancer tissues, and cell lines cultured without and with therapeutic agents, as well as from model reconstituted chromatins reveal that there may be different subsets of chromatin assemblage with specific patterns of histone replacement executing similar functions. In this light, we attempt to explain the intricate control system that maintains chromatin structure and dynamics during normal development as well as during tumor development and cancer progression in this review. Our focus is to highlight the contribution of H3K4 methylation-histone variant crosstalk in regulating chromatin architecture and subsequently its function.

Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic information in eukaryotes. DNA demethylation plays a very significant role during embryonic development and stands out for its contribution in molecular reconfiguration during cellular differentiation for determining stem cell fate. DNA demethylation arbitrated extensive make-over of the genome via reprogramming in the early embryo results in stem cell plasticity followed by commitment to the principal cell lineages. This article attempts to highlight the sequential phases and hierarchical mode of DNA demethylation events during enactment of the molecular strategy for developmental transition. A comprehensive knowledge regarding the pattern of DNA demethylation during embryogenesis and organogenesis and study of the related lacunae will offer exciting avenues for future biomedical research and stem cell-based regenerative therapy.

In the current era of genomic medicine, diseases are identified as manifestations of anomalous patterns of gene expression. Cancer is the principal example among such maladies. Although remarkable progress has been achieved in the understanding of the molecular mechanisms involved in the genesis and progression of cancer, its epigenetic regulation, particularly histone deacetylation, demands further studies. Histone deacetylases (HDACs) are one of the key players in the gene expression regulation network in cancer because of their repressive role on tumor suppressor genes. Higher expression and function of deacetylases disrupt the finely tuned acetylation homeostasis in both histone and non-histone target proteins. This brings about alterations in the genes implicated in the regulation of cell proliferation, differentiation, apoptosis and other cellular processes. Moreover, the reversible nature of epigenetic modulation by HDACs makes them attractive targets for cancer remedy. This review summarizes the current knowledge of HDACs in tumorigenesis and tumor progression as well as their contribution to the hallmarks of cancer. The present report also describes briefly various assays to detect histone deacetylase activity and discusses the potential role of histone deacetylase inhibitors as emerging epigenetic drugs to cure cancer.