Concise review on clinical applications of conditioned medium derived from human umbilical cord-mesenchymal stem cells (UC-MSCS)

In recent years, mesenchymal stem cells have provoked much attentiveness in the field of regenerative medicine because of their differentiation potential and the capability to facilitate tissue repair via the emancipation of biologically active molecules. They have gained interest because of their distinctive curative properties. Mesenchymal stem cells are isolated from the Wharton\u2019s jelly part of umbilical cord possessing higher proliferation capacity, immunomodulatory activity, plasticity, as well as self-renewal capacity than the mesenchymal stem cells from various origins, and it is considered to be the best resource for allogeneic transplantation. The isolated umbilical cord-derived mesenchymal stem cells are cultured in the Dulbecco\u2019s Modified Eagle\u2019s Medium, and thereby it begins to release soluble factors into the medium during the period of culture which is termed as conditioned medium. This conditioned media has both differentiation capacity and therapeutic functions. Thus, it can be able to differentiate the cells into different lineages and the paracrine effect of these cells helps in replacement of the damaged cells. This medium may accord to optimization of diagnostic and prognostic systems as well as the generation of novel and targeted therapeutic perspectives

Maternal obesity and gut microbiota are associated with fetal brain development

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternalfetal- placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother’s gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity and a high-fat diet in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed

Evidences of Protective Potentials of Microdoses of Ultra-High Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide

The present study was undertaken to examine if microdoses of ultra-high diluted arsenic trioxide (a potentized homeopathic remedy, Arsenicum Album 200C, diluted 10−400 times) have hepatoprotective potentials in mice subjected to repeated injections of arsenic trioxide. Arsenic intoxicated mice were divided into: (i) those receiving Arsenicum Album-200C daily, (ii) those receiving the same dose of diluted succussed alcohol (Alc 200C) and (iii) another group receiving neither drug nor succussed alcohol. Two other control groups were also maintained: one fed normal diet only and the other receiving normal diet and Alc-200C. Toxicity biomarkers like aspartate and alanine aminotransferases, glutathione reductase, catalase, succinate dehydrogenase, superoxide dismutase and reduced glutathione contents were periodically assayed keeping the observer “blinded”. Additionally, electron microscopic studies and gelatin zymography for matrix metalloproteinases of liver tissues were made at day 90 and 120. Blood glucose, hemoglobin, estradiol and testosterone contents were also studied. Compared to controls, Arsenicum Album-200C fed mice showed positive modulations of all parameters studied, thereby providing evidence of protective potentials of the homeopathic drug against chronic arsenic poisoning

role of heparin sodium salt in the modulation of human umbilical cord derived mesenchymal stem cell differentiation

Introduction: The present study aims to investigate the role of low molecular weight compound heparin sodium salt (HSS) to control the differentiation of the human umbilical cord (UC) derived mesenchymal stem cells (MSCs) through possible interaction with WWTR1 protein. Materials and Methods: In order to carry out this study, the human UC-derived stem cells were isolated and characterized by stem cell specific markers and the effect of HSS was studied by altering the phenotypes of MSCs. An Insilco approach was employed to reveal the structural determination of the ligand, the WWTR1 protein binding site and to predict the strength of the interaction. After HSS treatment, WWTR1, Oct4, nanog, SOX9 gene expressions were studied using real-time polymerase chain reaction (PCR). Cell staining was performed using alizarin red to confirm the formation of osteocytes. Results: Mineralization indicated by osteocytes was confirmed using alizarin red after the treatment of HSS. Post, HSS treatment, OCT4, Nanog, RUNX2, COL1A1 and WWTR1 gene expressions were positively modulated. Heparin treatment of MSCs lead to the up regulation of WWTR1 along with the down regulation of stemness markers Oct4 and Nanog expression. In silico studies also predicted the possible interaction of WWTR1 with HS. Results indicated that Amino acid residues ASP57, GLN83, GLN109, THR135, and TYR141 came up as a prominent interaction centre; ASP57, GLN83 and THR135 recorded the highest interaction energy – while ASP57 mostly participated in an electrostatic interaction. Conclusions: To conclude, it can be stated that heparin can possibly interact with WWTR1 along with having the capability to direct cells towards osteogenic lineages

Bioactive food components and their inhibitory actions in multiple platelet pathways

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets\u27 hemostatic and non-hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non-hemostatic disease are to be inhibited while leaving the platelet\u27s hemostatic function unaffected. Platelets\u27 anti-aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non-hemostatic activities are not well known. This review describes the hemostatic and non-hemostatic function of human blood platelets and the modulatory effects of bioactive food components. PRACTICAL APPLICATIONS: In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non-hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets\u27 complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact

A Follow-Up Study on the Efficacy of the Homeopathic Remedy Arsenicum album in Volunteers Living in High Risk Arsenic Contaminated Areas

In continuation of our short-term pilot studies reported earlier, results on certain toxicity biomarkers in volunteers who continued to take the potentized Arsenicum album 200C till 2 years are presented. Out of some 130 “verum”-fed volunteers of pilot study, 96 continued to take the remedy till 6 months, 65 till 1 year and 15 among them continued till 2 years. They provided samples of their urine and blood at 6 months, 1 year and finally at 2 years. None out of 17 who received “placebo” turned up for providing blood or urine at these longer intervals. Standard methodologies were used for determination of arsenic content in blood and urine, and for measurement of toxicity biomarkers like acid and alkaline phosphatases, alanine and aspartate amino transferases, lipid peroxidation and reduced glutathione and anti-nuclear antibody titers. Most of the volunteers reported status quo maintained after the improvement they achieved within the first 3 months of homeopathic treatment, in respect of their general health and spirit, and appetite and sleep. A few with skin symptoms and burning sensation, however, improved further. This was supported by the data of toxicity biomarkers, levels of all of which remained fairly within normal range. Therefore, administration of Arsenicum album 200C considerably ameliorates symptoms of arsenic toxicity on a long-term basis, and can be recommended for interim use, particularly in high risk remote villages lacking modern medical and arsenic free drinking water facilities. Similar studies by others are encouraged

MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis

Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease (CD) patients. MiR-155 in IMF was quantified by quantitative reverse transcription-PCR in basal condition and following exposure to TNF-alpha, interleukin (IL)-1 beta, lipopolysaccharide (LPS) or TGF-beta 1. The effects of miR-155 mimic or inhibitor transfection on cytokine release and suppressor of cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Regulation of the target gene SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We found that miR-155 was significantly upregulated in UC as compared with control-and CD-derived IMF. Moreover, TNF-alpha and LPS, but not TGF-beta 1 and IL-1 beta, significantly increased miR-155 expression in IMF. Ectopic expression of miR-155 in control IMF augmented cytokines release, whereas it downregulated SOCS1 expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly increased IL-6 and IL-8 release. In all, our data suggest that inflammatory mediators induce miR-155 expression in IMF of patients with UC. By downregulating the expression of SOCS1, miR-155 wires IMF inflammatory phenotype

Amelioration of Carcinogen-Induced Toxicity in Mice by Administration of a Potentized Homeopathic Drug, Natrum Sulphuricum 200

To examine if a potentized homeopathic drug, Natrum Sulphuricum 200 (Nat Sulph-200) has protective potentials against hepatocarcinogenesis, liver tumors were induced in mice through chronic feeding of P-dimethylaminoazobenzene (p-DAB; initiator of hepatocarcinogenesis) and phenobarbital (PB; promoter). Mice were divided into five sub-groups: fed normal low protein diet (Gr. I, normal control); fed normal low protein plus alcohol-200 (vehicle of the homeopathic remedy) (Gr. II); fed diet mixed with 0.06% p-DAB plus 0.05% PB (Gr. III); fed diet and carcinogens like Gr.III, plus alcohol 200 (positive control for drug fed mice) (Gr. IV) and fed diet and carcinogens like Gr. III, plus Natrum Sulphuiricum-200 (Gr. V; drug fed). Mice were sacrificed at day 7, 15, 30, 60, 90 and day 120 for study of cytogenetical endpoints like chromosome aberrations (CA), micronuclei (MN), mitotic index (MI) and sperm head anomaly (SHA) and biochemical toxicity parameters like aspartate amino transferase (AST), alanine amino transferase (ALT), acid (AcP) and alkaline (AlkP) phosphatases, lipid peroxidation (LPO) and reduced glutathione (GSH) content. Less number of liver tumors were observed in Gr. V (drug fed) mice. Administration of Nat Sulph 200 reduced genomic damage, activities of AcP, AlkP, AST, ALT, LPO and increased GSH content. Therefore, independent replication of the study by others is encouraged

Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression

Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1

Can Administration of Potentized Homeopathic Remedy, Arsenicum Album, Alter Antinuclear Antibody (ANA) Titer in People Living in High-Risk Arsenic Contaminated Areas? I. A Correlation with Certain Hematological Parameters

To examine whether elevated antinuclear antibody (ANA) titers reported in random human population of arsenic contaminated villages can be reverted to the normal range by administration of a potentized homeopathic drug, Arsenicum album, randomly selected volunteers in two arsenic contaminated villages and one arsenic-free village in West Bengal (India) were periodically tested for their ANA titer as well as various blood parameters in two types of experiments: ‘placebo-controlled double blind’ experiment for shorter duration and ‘uncontrolled verum fed experiment’ for longer duration. Positive modulation of ANA titer was observed along with changes in certain relevant hematological parameters, namely total count of red blood cells and white blood cells, packed cell volume, hemoglobin content, erythrocyte sedimentation rate and blood sugar level, mostly within 2 months of drug administration. Thus, Arsenicum album appears to have great potential for ameliorating arsenic induced elevated ANA titer and other hematological toxicities