RhoB expression associated with chemotherapy response and prognosis in colorectal cancer.

PURPOSE: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. MATERIALS AND METHODS: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. RESULTS: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. CONCLUSION: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

Endothelial dysfunction, platelet hyperactivity, hypertension, and the metabolic syndrome: molecular insights and combating strategies.

Metabolic syndrome (MetS) is a multifaceted condition that increases the possibility of developing atherosclerotic cardiovascular disease. MetS includes obesity, hypertension, dyslipidemia, hyperglycemia, endothelial dysfunction, and platelet hyperactivity. There is a concerning rise in the occurrence and frequency of MetS globally. The rising incidence and severity of MetS need a proactive, multipronged strategy for identifying and treating those affected. For many MetS patients, achieving recommended goals for healthy fat intake, blood pressure control, and blood glucose management may require a combination of medicine therapy, lifestyles, nutraceuticals, and others. However, it is essential to note that lifestyle modification should be the first-line therapy for MetS. In addition, MetS requires pharmacological, nutraceutical, or other interventions. This review aimed to bring together the etiology, molecular mechanisms, and dietary strategies to combat hypertension, endothelial dysfunction, and platelet dysfunction in individuals with MetS.

Association of MicroRNA-652 Expression with Radiation Response of Colorectal Cancer: A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy.

BACKGROUND: Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified microRNA-652 (miR-652) value on radiotherapy response and outcome in rectal cancer patients. METHODS: miR-652 expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of miR-652 with biological factors and the prognosis was examined. The biological function of miR-652 was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53+/+ and p53-/-) were used for in vitro study. The molecular interactions of miR-652 and tumor suppressor genes were studied through a computational approach. RESULTS: In RT patients, miR-652 expression was significantly decreased in cancers when compared to non-radiotherapy cases (P = 0.002). High miR-652 expression in non-RT patients was with increased apoptosis marker (P = 0.036), ATM (P = 0.010), and DNp73 expression (P = 0.009). High miR-652 expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation (P = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of miR-652 with apoptosis in rectal cancer. miR-652 expression in cancers was negatively related to WRAP53 expression (P = 0.022). After miR-652 inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53+/+ cells was significantly increased compared with HCT116 p53-/- cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable. CONCLUSION: Our findings suggest the potential value of miR-652 expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.

A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation.

Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin's potential use in colon cancer treatment.

Tumor Suppressor microRNAs in Gastrointestinal Cancers: A Mini-Review.

BACKGROUND: Gastrointestinal (GI) cancer is associated with a group of cancers affecting the organs in the GI tract, with a high incidence and mortality rate. This type of cancer development involves a series of molecular events that arise by the dysregulation of gene expressions and microRNAs (miRNAs). OBJECTIVES: This mini-review focuses on elucidating the mechanism of tumor suppressor miRNA-mediated oncogenic gene silencing, which may contribute to a better understanding of miRNA-mediated gene expression regulation of cell cycle, proliferation, invasion, and apoptosis in GI cancers. In this review, the biological significance of tumor suppressor miRNAs involved in gastrointestinal cancers is briefly explained. METHODS: The articles were searched with the keywords 'miRNA', 'gastrointestinal cancers', 'esophageal cancer', 'gastric cancer', 'colorectal cancer', 'pancreatic cancer', 'liver cancer', and 'gall bladder cancer' from the Google Scholar and PubMed databases. A total of 71 research and review articles have been collected and referred for this study. RESULTS: This review summarises recent research enhancing the effectiveness of miRNAs as novel prognostic, diagnostic, and therapeutic markers for GI cancer treatment strategies. The expression pattern of various miRNAs has been dysregulated in GI cancers, which are associated with proliferation, cell cycle regulation, apoptosis, migration, and invasion. CONCLUSION: The role of tumor suppressor miRNAs in the negative regulation of oncogenic gene expression was thoroughly explained in this review. Its potential role as a microRNA therapeutic candidate is also discussed. Profiling and regulating tumor suppressor miRNA expression in gastrointestinal cancers using miRNA mimics could be used as a prognostic, diagnostic, and therapeutic marker, as well as an elucidating molecular therapeutic approach to tumor suppression.

A Comprehensive Cancer-Associated MicroRNA Expression Profiling and Proteomic Analysis of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes.

BACKGROUND: The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. METHODS: Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and culture expanded. Subsequently, exosomes were isolated from hUCMSC conditioned medium and characterized by DLS, electron microscopy. Western blot for exosome surface marker protein CD63 expression was performed. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. RESULTS: The tri-lineage differentiation potential, fibroblastic morphology, and strong expression of pluripotency genes indicated that isolated fibroblasts are MSCs. The isolated extracellular vesicles were 133.8 ± 42.49 nm in diameter, monodispersed, and strongly expressed the exosome surface marker protein CD63. The miRNA expression profile and gene ontology (GO) depicted the differential expression patterns of high and less-expressed miRNAs that are crucial to be involved in the regulation of apoptosis. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. CONCLUSION: Primary human MSCs released miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs have a critical influence in regulating cell death and apoptosis of cancer cells.

Molecular Characterization of Primary and Metastatic Colon Cancer Cells to Identify Therapeutic Targets with Natural Compounds.

BACKGROUND: Metastasis is the world's leading cause of colon cancer morbidity. Due to its heterogeneity, it has been challenging to understand primary to metastatic colon cancer progression and find a molecular target for colon cancer treatment. OBJECTIVES: The current investigation aimed to characterize the immune and genotypic profiles of primary and metastatic colon cancer cell lines and identify a molecular target for colon cancer treatment. METHODS: Colony-forming potential, migration and invasion potential, cytokine profiling, miRNA, and mRNA expression were examined. Molecular docking for the Wnt signaling proteins with various plant compounds was performed. RESULTS: Colony formation, migration, and invasion potential were significantly higher in metastatic cells. The primary and metastatic cells' local immune and genetic status revealed TGF ß-1, IL-8, MIP-1b, I-TAC, GM-CSF, and MCP-1 were highly expressed in all cancer cells. RANTES, IL-4, IL- 6, IFNγ, and G-CSF were less expressed in cancer cell lines. mRNA expression analysis displayed significant overexpression of proliferation, cell cycle, and oncogenes, whereas apoptosis cascade and tumor suppressor genes were significantly down-regulated in metastatic cells more evidently. Most importantly, the results of molecular docking with dysregulated Wnt signaling proteins shows that peptide AGAP and coronaridine had maximum hydrogen bonds to ß-catenin and GSK3ß with a better binding affinity. CONCLUSION: This study emphasized genotypic differences between the primary and metastatic colon cancer cells, delineating the intricate mechanisms to understand the primary to metastatic advancement. The molecular docking aided in understanding the future molecular targets for bioactive- based colon cancer therapeutic interventions.

Vitagenic Effect of Specific Bioactive Fractions of Rhodiola with Trachurus sp. Extract Against Oxidative Stress-Induced Aging in Human Amnion Derived Epithelial Cell Line: In View of a Novel Senolytic.

BACKGROUND: Rhodiola rosea is a herb that has been used in traditional medicine for several years, and LF is a class of lipoproteins derived from the fish Trachurus sp. (LF-T), which exhibits known anti-inflammatory activity. OBJECTIVE: Investigating the anti-aging effect of Rhodiola specific bioactive fractions cluster in combination with LF-T (R-L compound) in H2O2 mediated oxidative stress-induced human amnion derived epithelial cell line - FL cells as normal human cell line. METHODS: FL cells were treated with H2O2 to induce cellular aging, followed by treatment of the RL compound to study its anti-aging characteristics. Based on the proliferation rate, 0.05% and 0.1% concentration of R-L compound was determined using MTT assay. Anti-aging and anti-oxidant assays, ABTS, DPPH, Hyaluronidase activity Nitric Oxide, Lipid Peroxidase, and Superoxide Dismutase were performed. qPCR for anti-aging genes and matrix metalloproteinase genes were analyzed. RESULTS: FL cells treated with R-L compound exhibited increased proliferation rate and free-radical reduction. Decreased Hyaluronidase enzyme activity and regulation of genes such as SIRT1, KLOTHO, SERPINA 6, MMP 9, and MMP 2 expression depicted the anti-aging role of the R-L compound. Chemometric profiling of the R-L compound revealed that aromatic compounds and unsaturated fatty acids along with their derivatives, were present predominantly, which might have attributed to the potent oxidative stress impeded aging activity. CONCLUSION: Specific Bioactive Fractions of Rhodiola in combination with LF-T obtained from Trachurus sp. involve in the regulation of aging genes and might be a novel approach to prevent the cells from oxidative stress damage and also it might avert the aging of cells.

A Review of AEG-1 Oncogene Regulating MicroRNA Expression in Colon Cancer Progression.

MicroRNAs are a class of small non-coding RNAs that perform a crucial function in posttranscriptional gene regulation. Dysregulation of these microRNAs is associated with many types of cancer progression. In tumorigenesis, downregulated microRNAs might function as a tumour suppressor by repressing oncogenes, whereas overexpressed miRs might function as oncogenes by suppressing tumour suppressor. Similarly, Metadherin (also known as AEG-1/ LYRIC), is an oncogene, the levels of which are found to be very high in various cancers and play a crucial role in the proliferation of cells and invasion. Our review focuses on the study, which shows the alteration of microRNA expression profile and suppression of carcinogenesis when MTDH/AEG-1 is targeted. It summarises the studies where downregulation and upregulation of AEG-1 and microRNAs, respectively, alter the biological functions of the cell, such as proliferation and apoptosis. Studies have reported that AEG-1 can be direct or indirect target of microRNA, which could provide a new-insight to know the underlying molecular mechanism and might contribute to the progress of new therapeutic strategies for the disease.

Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes.

OBJECTIVES: Wound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT). METHODS: Firstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed. RESULTS: Increased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5-6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1). CONCLUSIONS: Our results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells.

Background Colorectal cancer (CRC) is the third most prevalent form of cancer and fourth leading cause of morbidity worldwide. Surgical resection remains the only curative approach for CRC, but recurrence following surgery is the main problem and ultimate cause of death. Lycopodium clavatum and quercetin have been found to exert its anticancer properties. The aim of the present study is to investigate whether quercetin or L. clavatum extract and combination of both have any profound role in reducing major inflammatory cytokines in Colo-320 cells. Methods L. clavatum and Quercetin alone or in combination was administered to colon cancer cells and various toxicity markers, gene expression analyses of apototic genes and gelatin zymmography were performed. Results Quercetin (50 µm) in combination with L. clavatum extract (10 µL) distinctly reduced cell growth and highlighted their potential effects in extirpation of colon cancer cells. Treatment with increased dose of L. clavatum extract in combination with quercetin reduced the colony size and proliferation potential when compared to the sole treatment of plant extracts. In the antimicrobial assays, it was observed that Lycopodium alone exhibited antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Characterization of L. clavatum extract and quercetin was performed and confirmed the presence of flavonoids and alkaloids. Treatment with Lycopodium and quercetin combination induced significant down-regulation in activities of MMP2 and MMP9 tested by gelatin zymography. The combined treatment greatly affected the mRNA expression of p53, Bcl2, Bax, Caspase 3, Wnt 1, Cyclin D1, and Catalase genes in colon cancer cells. Conclusion The synergistic effect between Lycopodium and quercetin might bring forward the enhanced antitumorigenic properties of combinational therapy with natural products to successfully combat the cancer progression with minimal side effects and resistance to drugs.

Benefits of aged garlic extract in modulating toxicity biomarkers against p-dimethylaminoazobenzene and phenobarbital induced liver damage in Rattus norvegicus.

Garlic (Allium sativum L.), a popular spice, has been used for decades in treating several medical conditions. Although Allicin, an active ingredient of garlic has been extensively studied on carcinogen-induced hepatotoxicity and oxidative stress in rats (Rattus norvegicus), no systematic study on the beneficial effects of generic aged garlic and specific aged garlic extract-Kyolic has been done. The present study involves rats fed chronically with two liver carcinogens, p-dimethylaminoazobenzene and phenobarbital, to produce hepatotoxicity. The aged garlic extract was characterized by UV-spectra, FTIR, HPLC and GC-MS. Biochemical and pathophysiological tests were performed by keeping suitable controls at four fixation intervals, namely, 30, 60, 90, and 120 days, utilizing several widely accepted toxicity biomarkers. Compared to the controls, remarkable elevation in the activities of lactate dehydrogenase, gamma glutamyl transferase and decline in catalase and glucose-6-phosphate dehydrogenase were observed in the carcinogen fed rats. Daily administration of aged garlic extract, could favorably modulate the elevated levels of various toxicity biomarkers including serum triglyceride, creatinine, urea, bilirubin, blood urea nitrogen except total cholesterol. It also altered the levels of blood glucose, HDL-cholesterol, albumin, AST, ALT, and hemoglobin contents in carcinogen intoxicated rats, indicating its protective potential against hepatotoxicity and oxidative stress in the experimental rats. Down-regulation of Bcl-2 and p53 proteins caused cell cycle arrest and apoptosis in garlic fed group. Kyolic exhibited additional benefits by arresting cell viability of cancer cells. This study would thus validate the use of aged garlic extract in the treatment of diseases causing liver toxicity including hepatocarcinoma.

Wnt signaling regulates the proliferation potential and lineage commitment of human umbilical cord derived mesenchymal stem cells.

Relatively less is known about the interactions that tightly regulate the mesenchymal stem cells (MSCs) to maintain their pluripotency. Recent studies reports that Wnt proteins might play an important role in governing the MSC cell fate. In this study, we tested the hypothesis that Wnt proteins differentially regulate in vitro differentiation of human umbilical cord derived MSCs. Stromal cells from human umbilical cord (hUCMSCs) were isolated and treated with Wnt inhibitor/activator. FACS analysis of hUCMSCs for CD29, CD90, CD73, CD44, CD45 marker expression and gene expression of Wnt target genes and lineage specific genes were performed after Lithium Chloride (LiCl) and Quercetin treatment for 6 days. The cultured primary hUCMSCs demonstrated elevated MSC surface marker expression with clonogenic properties and differentiation potentials towards osteogenic, adipogenic and chondrogenic lineages. Downregulation in the expression of Wnt with Quercetin treatment was noted. LiCl treatment increased cellular proliferation but did not influence differentiation suggesting that the cells retain pluripotency whereas Quercetin treatment downregulated stemness markers, Wnt target gene expression and promoted osteogenesis as demonstrated by FACS analysis, calcium estimation and gene expression studies. Shift of differentiation potential after the inhibition of Wnt signaling by Quercetin was evident from the gene expression data and elevated calcium production, driving MSCs towards probable osteogenic lineage. The findings in particular are likely to open an interesting avenue of biomedical research, summarizing the impact of Wnt signaling on lineage commitment of MSCs.

Targeting Wnt Signaling through Small molecules in Governing Stem Cell Fate and Diseases.

BACKGROUND: The conserved Wnt/ß-catenin signaling pathway is responsible for multiple functions including regulation of stem cell pluripotency, cell migration, self-renewability and cell fate determination. This signaling pathway is of utmost importance, owing to its ability to fuel tissue repair and regeneration of stem cell activity in diverse organs. The human adult stem cells including hematopoietic cells, intestinal cells, mammary and mesenchymal cells rely on the manifold effects of Wnt pathway. The consequences of any dysfunction or manipulation in the Wnt genes or Wnt pathway components result in specific developmental defects and may even lead to cancer, as it is often implicated in stem cell control. It is absolutely essential to possess a comprehensive understanding of the inhibition and/ or stimulation of the Wnt signaling pathway which in turn is implicated in determining the fate of the stem cells. RESULTS: In recent years, there has been considerable interest in the studies associated with the implementation of small molecule compounds in key areas of stem cell biology including regeneration differentiation, proliferation. In support of this statement, small molecules have unfolded as imperative tools to selectively activate and inhibit specific developmental signaling pathways involving the less complex mechanism of action. These compounds have been reported to modulate the core molecular mechanisms by which the stem cells regenerate and differentiate. CONCLUSION: This review aims to provide an overview of the prevalent trends in the small molecules based regulation of stem cell fate via targeting the Wnt signaling pathway.

A Review on Theragnostic Applications of Micrornas and Long Non- Coding RNAs in Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.

Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC).

Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

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's 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's Modified Eagle's 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.