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Background The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. Main body Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells. Conclusions The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.

Sustainable food supply to the world is possibly the greatest challenge that human civilization has ever faced. Among animal sourced foods, meat plays a starring role in human food chain. Traditional meat production necessitates high proportion of agricultural land, energy and clean water for rearing meat-producing animals; also massive emission of greenhouse gases from the unutilized nutrients of the digestive process into the environment is a major challenge to the world. Also, conventional meat production is associated with evolution and spread of superbugs and zoonotic infections. In vitro meat has the potential to provide a healthy alternative nutritious meal and to avoid the issues associated with animal slaughtering and environmental effects. Stem cell technology may provide a fascinating approach to produce meat in an animal-free environment. Theoretically, in vitro meat can supplement the meat produced by culling the animals and satisfy the global demand. This article highlights the necessity and potential of stem cell-derived in vitro meat as an alternative source of animal protein

The exponential growth of pollutant discharges into the environment due to increasing industrial and agricultural activities is a rising threat for human health and a biggest concern for environmental health globally. Several synthetic chemicals, categorized as potential environmental endocrine-disrupting chemicals (EDCs), are evident to affect the health of not only livestock and wildlife but also humankind. In recent years, human exposure to environmental EDCs has received increased awareness due to their association with altered human health as documented by several epidemiological and experimental studies. EDCs are associated with deleterious effects on male and female reproductive health; causes diabetes, obesity, metabolic disorders, thyroid homeostasis and increase the risk of hormone-sensitive cancers. Sewage effluents are a major source of several EDCs, which eventually reach large water bodies and potentially contaminate the drinking water supply. Similarly, water storage material such as different types of plastics also leaches out EDCs in drinking Water. Domestic wastewater containing pharmaceutical ingredients, metals, pesticides and personal care product additives also influences endocrine activity. These EDCs act via various receptors through a variety of known and unknown mechanisms including epigenetic modification. They differ from classic toxins in several ways such as low-dose effect, non-monotonic dose and trans-generational effects. This review aims to highlight the hidden burden of EDCs on human health and discusses the non-classical toxic properties of EDCs in an attempt to understand the magnitude of the exposome on human health. Present data on the environmental EDCs advocate that there may be associations between human exposure to EDCs and several undesirable health outcomes that warrants further human bio-monitoring of EDCs.

Nanomedicine is the spin-off of modern medicine and nanotechnology and aims to prevent and treat diseases using nanoscale materials such as biocompatible nanoparticles and nanorobots. Targeted cellular and tissue-specific clinical applications with maximal therapeutic effects and insignificant side effects could be achieved by the pursuit of nanotechnology in medicine and healthcare regimen. The majority of conventional cancer therapies eliminate the cells of the tumor but not the cancer stem cells (CSCs). Conversely, the use of nanotechnology in CSC-based therapies is an emerging field of biomedical sciences. This article summarizes the recent trends and application of nanomedicine especially in CSC therapy along with its limitations.

Stem cell niche is a specialized and dynamic microenvironment around the stem cells which plays a critical role in maintaining the stemness properties of stem cells. Over the years, advancement in the research activity has revealed the various important aspects of stem cell niche including cell-cell interaction, cell-extracellular matrix interaction, a large number of soluble signaling factors and various biochemical and biophysical cues (such as oxygen tension, flow, and shear and pore size). Stem cells have the potential to be a powerful tool in regenerative medicine due to their self-renewal property and immense differentiation potential. Recent progresses in in vitro culture conditions of embryonic stem cells, adult stem cells and induced pluripotent stem cells have enabled the researchers to investigate and understand the role of the microenvironment in stem cell properties. The engineered artificial stem cell niche has led to a better execution of stem cells in regenerative medicine. Here we elucidate the key components of stem cell niche and their role in niche engineering and stem cell therapeutics.

Embryonic pluripotent stem cells (ePSCs) can generate all somatic cell types, as well as functional gametes. In mouse and rat, derivation of ePSCs from the early epiblast is promoted by the double inhibition ("2i") of mitogen-activated protein kinase kinase (MAP2K), antagonizing fibroblast growth factor signaling (FGF), and glycogen synthase kinase 3 (GSK3), stimulating the WNT pathway. However, it has remained unclear whether this culture regime is applicable to nonrodent livestock species. Here we report the generation of bovine ePSCs under minimal conditions. Inner cell masses (ICMs) were immunosurgically isolated from in vitro fertilized bovine blastocysts and cultured feeder-free in 2i medium. Dual kinase inhibition primed bovine ICMs for stem cell derivation and sustained expression of epiblast-specific pluripotency markers SOX2 and NANOG, while repressing the hypoblast marker GATA4. Following mechanical passage, 2i supported limited proliferation for several weeks. Continuously cultured ePSC lines expressed discriminatory markers of naïve pluripotency and primordial germ cells, but not of primed epiblast stem cells. In female ePSCs, most OCT4-positive cells lacked epigenetically silenced X-chromosomes, displaying a diagnostic feature of naïve pluripotency. Bovine ePSCs maintained a normal karyotype and differentiated into derivatives of all three germ layers in suspension culture. This culture system provides a screening platform for factors that maintain long-term proliferation of pluripotent embryonic cattle cells without genetic intervention.

Objective: The effects of Lactobacillus rhamnosus GG (LGG) and Aloe vera (AV) gel on lipid profiles in rats with induced hypercholesterolemia were studied. Methods: Five treatment groups of rats (n ¼ 7) were the fed experimental diets: a normal control diet, a hypercholesterolemic diet (HD), HD þ LGG, HD þ AV gel, and HD þ LGG þ AV gel. Results: Supplementation with LGG decreased serum total cholesterol by 32%; however, in combination with AV, the decrease was 43%. The decreases in triacylglycerol levels in the HD þ LGG, HD þ AV, and HD þ LGG þ AV groups were 41%, 23% and 45%, respectively. High-density lipoprotein increased by 12% in the HD þ LGG þ AV group, whereas very low-density and lowdensity lipoprotein values decreased by 45% and 30%, respectively. The atherogenic index in the HD þ LGG þ AV group decreased to 2.45 from 4.77 in the HD þ LGG group. Furthermore, fecal Lactobacillus species counts increased significantly when LGG was fed in combination with the AV gel. The oral administration of LGG fermented milk alone or in combination with the AV gel increased cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase expression) and absorption (low-density lipoprotein receptor expression), whereas cholesterol 7 a-hydroxylase mRNA expression levels were lower in the HD þ LGG and HD þ LGG þ AV groups compared with the control HD group. Conclusion: The combination of LGG and AV gel may have a therapeutic potential to decrease cholesterol levels and the risk of cardiovascular diseases.

Heterogeneous amniotic fluid contains various cell types. The aim of this study was to characterize and differentiate some of the key stemness attributes of the amniotic fluid-derived cells in buffalo (Bubalus bubalis). The amniotic fluid (AF) cells were cultured without feeder cells, in DMEM containing 15% FBS, 1% non-essential amino acids, 1% penicillin/streptomycin/ampicillin, 1% vitamin solution, and 1% l-glutamine in 5% CO(2) in humidified air at 38.5±0.5 °C. After 6 days of culture different types of cells viz., star shaped (62.7%), spherical without nucleus (1.9%), spherical with nucleus (26.4%), pentagonal (0.4%), and free floating/rounded cells (8.3%) were observed. Most of the cells started anchorage-dependent growth after day 7 of the culture. Expression of alkaline phosphatase (AP) and Oct-4, Nestin and FGF-5 were observed from the AF cells at different passages. Using species-specific primers, a PCR amplicon of 200, 296 and 210 bp were observed for Oct-4, Nestin and FGF-5, respectively. The cells were found to have a normal karyotype at different passages. These results may contribute towards establishing non-embryonic pluripotent stem cells for various therapeutic and reproductive biotechnological applications in the species.

Inflammation is viewed as one of the major causes for the development of different diseases like cancer, cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, asthma, and CNS related diseases such as depression and parkinson's disease; and this fervent phenomenon provides space for understanding different inflammatory markers. Increasing evidences have elucidated the outcome of inflammatory pathways dysregulation resulting in many symptoms of chronic diseases. The detection of transcription factors such as nuclear factor kappa-B (NF-κB), STAT and their gene products such as COX-2, cytokines, chemokines and chemokine receptors has laid molecular foundation for the important role of inflammation in chronic diseases in which the NF-κB is reported as a major mediator which makes a possible way for the development of new therapeutic approaches using synthetic and natural compounds that might eventually decrease the prevalence of these diseases. Even if many inflammatory markers like TNF-α, IL-1, IL-6, IL-8 and C-reactive protein (CRP) are reported to be the major key factors with proved role in several inflammatory diseases, IL-1 and TNF-α are the important cytokines that can induce the expression of NF-κB which is the potential target in these inflammatory diseases. This review aims to explore and summarize that how some drugs and natural compounds show their modulatory activity in inflammatory pathways and chronic inflammatory markers in these inflammatory diseases.

The aim of this study was to investigate the chemopreventive effect of probiotic fermented milk and chlorophyllin on aflatoxin B₁ (AFB₁) induced hepatocellular carcinoma. In vivo trials were conducted on 200 Wistar rats allocated to eight groups. Rats in the positive control group were given intraperitoneal injection of aflatoxin B₁ at 450 μg/kg body weight twice a week for 6 weeks. The rats were sacrificed and dissected at 25th week of the experiment, and comet assay was carried out in hepatic cells to assess the genotoxicity or DNA damage. The tumour incidence was decreased by approximately one-third than AFB₁ control group. The expression of c-myc bax, bcl-2, cyclin D1, p53 and rasp-21 genes was also studied. A significant (P0.05) reduction in DNA damage was observed in probiotic fermented milk with chlorophyllin group as compared to aflatoxin B₁ control group. The c-myc, bcl-2, cyclin D1 and rasp-21 level was found to be highest in AFB₁ control group as compared to the treatment group. The results advocate the enhanced protective potential of probiotic fermented milk and chlorophyllin against AFB₁-induced molecular alterations in hepatic cells during carcinogenesis.

Authentic induced pluripotent stem cells (iPSCs), capable of giving rise to all cell types of an adult animal, are currently only available in mouse. Here, we report the first generation of bovine iPSC-like cells following transfection with a novel virus-free poly-promoter vector. This vector contains the bovine cDNAs for OCT4, SOX2, KLF4 and c-MYC, each controlled by its own independent promoter. Bovine fibroblasts were cultured without feeders in a chemically defined medium containing leukaemia inhibitory factor (LIF) and inhibitors of MEK1/2 and glycogen synthase kinase-3 signaling (‘2i’). Non-invasive real-time kinetic profiling revealed a different response of bovine vs human and mouse cells to culture in 2i/LIF. In bovine, 2i was necessary and sufficient to induce the appearance of tightly packed alkaline phosphatase-positive iPSC-like colonies. These colonies formed in the absence of DNA synthesis and did not expand after passaging. Following transfection, non-proliferative primary colonies expressed discriminatory markers of pluripotency, including endogenous iPSC factors, CDH1, DPPA3, NANOG, SOCS3, ZFP42, telomerase activity, Tra-1-60/81 and SSEA-3/4, but not SSEA-1. This indicates that they had initiated a self-sustaining pluripotency programme. Bovine iPSC-like cells maintained a normal karyotype and differentiated into derivatives of all three germ layers in vitro and in teratomas. Our study demonstrates that conversion into induced pluripotency can occur in quiescent cells, following a previously undescribed route of direct cell reprogramming. This identifies a major species-specific barrier for generating iPSCs and provides a chemically defined screening platform for factors that induce proliferation and maintain pluripotency of embryo-derived pluripotent stem cells in livestock.

Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes beta-glucuronidase and beta-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory oxidative stress that protects cells against carcinogen-induced damage. These include glutathione-S-transferase, glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. However, there is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence based largely on laboratory studies.

The swamp buffalo holds tremendous potential in the livestock sector in Asian and Mediterranean countries. Current needs are the faster multiplication of superior genotypes and the conservation of endangered buffalo breeds. Recent advances in assisted reproductive technologies, including in vitro embryo production methodologies, offer enormous opportunities to not only improve productivity, but also to use buffaloes to produce novel products for applications to human health and nutrition. The use of molecular genomics will undoubtedly advance these technologies for their large-scale application and resolve the key problems currently associated with advanced reproductive techniques, such as animal cloning, stem cell technology and transgenesis. Preliminary success in the application of modern reproductive technologies warrants further research at the cellular and molecular levels before their commercial exploitation in buffalo breeding programmes.

Microbial metagenomics—the applications of the genomics suit of technologies to nonculturable microorganisms, is coming of age. These approaches can be used for the screening and identification of nonculturable gastrointestinal (GI) microflora for assessing and exploiting them in nutrition and the health of the host. Advances in technologies designed to access this wealth of genetic information through environmental nucleic acids extraction and analysis have provided the means of overcoming the limitations of conventional culture-dependent microbial genetic exploitation. The molecular techniques and bioinformatics tools will result in reliable insights into the animals’ GI microbial structure and activity of the livestock gut microbes in relation to functional interactions, temporal and spatial relationships among different microbial consortia and dietary ingredients. Further developments and applications of these methods promise to provide the opportunity to link distribution and identity of various GI microbes in their natural habitats, and explore their use for promoting livestock health and industrial development.

Degenerating changes after long durations of denervation have been studied in frog motor end-plate. During the 2nd month of denervation, the Schwann cell undergoes fissuration and the post-synaptic membrane displays the presence of furrows. The extent of the furrows in the post-synaptic membrane and fissuration of Schwann cell increases with increasing periods of denervation. The formation of furrows seem to be correlated with fissure formation in the Schwann cell cytoplasm. During the 4th month of denervation, at places, sequestration of postsynaptic fold from parent muscle occurs. The furrows in the postsynaptic membrane are eventually responsible for the sequestration of folds. In spite of the remarkable morphological changes at certain end-plates after long periods of denervation, the percentage of end-plates displaying spontaneous activity remains the same during this period (3-4 months) as after short periods of denervation (I2 months). This permits us to conclude that only at certain end-plate regions is the Schwann cell capable of producing acetylcholine responsible for miniature endplate potentials (min. e.p.p.s.) and this capacity is maintained until very long periods.

It is known that, in a denervated striated muscle, the satellite cells multiply by mitotic division. A liaison between these satellite cells and the Schwann cell in front of the post-synaptic membrane in denervated frog muscle has been observed. It is probable that such cell connections help in the subsistence of the Schwann cell in a denervated muscle.

The mechanism of re-innervation depends on the period of denervation. After 2 1/2 months, when post-synaptic folds are intact but for the furrows, the reinner vation takes place at the former synaptic sites. The Schwann cell which is present in contact with the post-synaptic membrane till that time is withdrawn at the moment of reinnervation and the terminal bouton establishes contact with it. After 4 months of denervation, the post-synaptic sites are not always intact; at places there is sequestration and hence flattening of the folds. Thus, the reinnervation takes place, firstly, at old synaptic gutters where the synaptic sites are intact and secondly, by the formation of new neuromuscular junctions. The latter is marked by the specialisation of the parts of muscular membrane before the nerve is in contact with it. The process of reinnervation is gradual after short durations and is rapid after long durations. Similarly, the reappearance of the electric activity is gradual after short and abrupt after long durations. The miniature end-plate potentials (min. e.p.p.s.) in recently innervated muscle in both cases are characterised by their slow time course but normal in their frequency and distribution of the amplitudes. In case of some fibres, the min. e.p.p.s. had Gaussian as well as skewed amplitude distribution. This could be due to the unequal receptivity of the ACh or to the liberation of cholinesterases in variable amounts. The newly formed end-plates are capable of functionning before acquiring their normal morphological characters.

Structural and functional behaviour of motor end-plates after transection of the motor nerve has been studied in two species of frog: Rana esculenta and Rana temporaria. The physiological results show that in both species there is a transient cessation of spontaneous activity followed by a resumption of miniature end-plate potentials (min. e.p.p.s.) after denervation. The characteristics of these potentials (frequency, distribution of amplitudes, time-course) are similar in the two species. However, some differences have been observed: Firstly, the period of silence lasts for 2--4 days in the case of Rana temporaria whereas it is prolonged to about 15 days in Rana esculenta. Secondly, the resumption of min. e.p.p.s. is gradual and after the 10th day of denervation remains constant in Rana temporaria. It is inconstant independent of the period of denervation in Rana esculenta. The morphological results show that the Schwann cell is constantly in contact with the post-synaptic membrane after about 6 days of denervation in both species. It is suggested that either the Schwann cell is capable of functioning for a limited period of time in Rana esculenta or is activated to produce min. e.p.p.s. only in certain cases.

The frog skeletal muscle resists atrophy for a long time after denervation. If, however, the entry of the nerve is prevented for more than 3.5 months, small muscle portions, sometimes containing nucleus, are sequestered from the parent muscle fibre. The basal lamina does not dissociate from these detached muscle portions.