Filtenborglopez6575
nt vaccines may be an option worthy of clinical testing.
Breast Cancer (BC), a common death-causing disease and the deadliest cancer next to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy is marked by targeting the activities of some receptors such as Estrogen Receptor alpha (ER-α). At present, one of the most commonly used and approved marketed therapeutic drug for BC is tamoxifen. Despite the short term success of tamoxifen usage, its long time treatment has been associated with significant side effects. Therefore, there is a pressing need for the development of novel anti-estrogens for the prevention and treatment of BC.
In this study, we evaluate the inhibitory effect of Cannabis Sativa phyto-constituents on ER-α.
Glide and Induced Fit Docking followed by ADME, Automated QSAR and Binding free energy (ΔGbind) studies were used to evaluate the anti-breast cancer and ER-α inhibitory activity of Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.
Phyto-constituents of Cannabis sativa possess lower docking scores and good ΔGbind when compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds demonstrated the properties required to make them promising therapeutic agents.
The results of this study suggest that Naringenin, Dihydroresveratrol, Baicalein, Apigenin and Cannabitriol could have relatively better inhibitory activity than tamoxifen and could be a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo and/or in vitro assays could be conducted to attest the ability of these compounds.
The results of this study suggest that Naringenin, Dihydroresveratrol, Baicalein, Apigenin and Cannabitriol could have relatively better inhibitory activity than tamoxifen and could be a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo and/or in vitro assays could be conducted to attest the ability of these compounds.
m6A-methyltransferaseMETTL3 anddemethylaseFTO regulate gene expressionby dynamically modifying RNAmethylation. However, theirclinical relevancein renal Clear Cell Carcinoma (CCRCC) hasnotbeenwell elucidated.
This study aimsto investigate prognostic values of FTO and METTL3mRNA and DNA methylation, their differential expression andassociations with chemokines and inflammation-related genes in CCRCC.
Kaplan-Meier survival curves and multivariate cox regression were performed for survival analyses, and random-effects meta-analysis was for differential expression of FTO and METTL3 in CCRCC.
A significantly negative correlation existed between mRNA and DNA methylation for bothFTOandMETTL3.Survival analysis showed a superior survival in patients with either high FTOmRNA or low DNA methylation,or low METTL3mRNA or high DNA methylation. The adjusted hazard ratios were 0.67 (95% CI 0.49-0.91, p=0.01) for high vs. low FTOmRNA, 2.17 (1.38-3.42, p=0.0008) for high vs. low FTODNA methylation, 1.97 (1.45-2.68, p<0.0001) for high vs. low METTL3mRNA, and 0.49 (0.31-0.79, p=0.003) for high vs. low METTL3DNA methylation, respectively. There was a significant interaction between FTO and METTL3mRNA levels (p =0.024). Upregulation of FTO and METTL3 with 1.64 folds (95% CI 1.43-1.89) and 1.17 folds (1.02-1.35), respectively, was observed in CCRCCvs. normal kidney tissues.FTO and METTL3mRNA had opposite direction in association with the expression of CD8+ T cell migration-relatedchemokines.
Dysregulated FTO and METTL3may beinvolved in the disease development and progression,and affect immune response in CCRCC.FTO and METTL3 expression and DNA methylation are potential prognostic markers of CCRCC.
Dysregulated FTO and METTL3may beinvolved in the disease development and progression,and affect immune response in CCRCC.FTO and METTL3 expression and DNA methylation are potential prognostic markers of CCRCC.
E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo.
We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). .
Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry.
The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products.
These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).
These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).Bone regeneration is a critical problem in modern clinical practice. Osteocytes are the most abundant cell population of mature adult bone that plays major roles in the regulation of bone formation. In humans, the segmental bone defects cannot be repaired by endogenous regenerative mechanisms. Bone tissue engineering (BTE) is a promising option for the treatment of difficult segmental and skeletal defects. BTE requires suitable cell sources with rapid expansion and adequate function, inducible factors, and scaffolds, to successfully regenerate or repair the bone injury. To overcome the disadvantages of using allogeneic and autologous tissue grafts, stem cell-based therapy has progressed an advanced topic in regenerative medicine. In the past few decades, numerous attempts have been made to generate osteocytes by using pluripotent stem cells (PSCs) for repair and regeneration of bone defects. Human induced pluripotent stem cells (hiPSCs) are PSCs that can self-renew and differentiate into a variety of cell types. Reprogramming of human somatic cells into hiPSCs provides a new opportunity for regenerative medicine, cell-based drug discovery, disease modeling, and toxicity assessment. The ability to differentiate hiPSCs towards mesenchymal stem cells (iPSC-MSCs) is essential for treating bone-related damages and injuries. Several in vitro studies revealed that the cell type of origin for iPSCs, a combination of transcription factors, the type of promoter in the vector, transduction methods, scaffolds, differentiating techniques, and culture medium may affect the osteogenic differentiation potential of hiPSCs. This review will focus on several factors that influence the osteogenic differentiation of human iPSCs.
Cancer stem cells (CSCs) are small subpopulation of cells within tumors and play significant roles in tumorigenesis, metastasis, resistance to treatment and relapse. They are defined by self-renewal and multi-lineage differentiation and aggressiveness. Epigenetic modifications including DNA methylation and acetylation, histone modifications and non-coding RNAs (ncRNAs) are partly responsible for CSC potentials and are involved in the modification of key components of crucial pathways such as Notch and Wnt signaling in breast cancer.
In this review, we present an overview of the pathways and epigenetic events that lead to the transformation of mammary gland stem cells to breast CSCs (BCSCs). Based on the data presented here, important pathways such as TGF-β/SMAD2 and Wnt/β-catenin and epigenetic modifications including histone modifications, DNA methylations and microRNAs play important roles in BCSC formation and maintenance.
Epigenetic events can alter expression of genes and functional RNAs resulting in tumor initiation and progression. Thus, better understanding of epigenetic modifications involved in BCSC maintenance signaling pathways may help to eliminate or suppress BCSCs and overcome cancer by generating more effective and efficient therapeutic agents.
Epigenetic events can alter expression of genes and functional RNAs resulting in tumor initiation and progression. Thus, better understanding of epigenetic modifications involved in BCSC maintenance signaling pathways may help to eliminate or suppress BCSCs and overcome cancer by generating more effective and efficient therapeutic agents.Bone is a hard but dynamic organ that is constantly remodeled throughout the life process. The dynamic balance between bone resorption and bone formation is very important. Mesenchymal stem cells (MSCs) have the abilities of self-renewal and pluripotent differentiation; therefore, their roles as the promising tool for treatment of osteoporosis and other diseases have become focus in regenerative medicine in recent years. Over the past years, histone methylation has been recognized as a major player in the regulation of osteogenic differentiation of MSC. In this review, we highlight the recent research progress of histone methylation modification and its possible involvement in MSC osteogenesis.Recent evidence confirms that not each tumor cell is proficient in instigating a tumor. Merely a small part of the cancer cells, so-called cancer stem cells (CSCs), can produce cancer indistinguishable from the first one. CSC model has been recognized as a cellular component that adds to phenotypic and functional heterogeneity in different cancers. Latest explanations have featured numerous complexities and difficulties like CSC phenotype that can differ extensively between patients. Tumors may harbor various phenotypically or genetically specific CSCs, and consequently, metastatic CSCs can develop from vital CSCs and tumor cells. Scientists have discovered a few markers for CSCs. The recent finding reveals that CSCs are resistant to radiotherapy and chemotherapy and may clarify the disease's reappearance. Minimal amounts of CSCs can repopulate a tumor. Subsequently, it is essential to understand the attributes and mechanisms by which CSCs show their resistance to therapeutic agents. These aptitudes contribute to new bits of knowledge that gives better therapeutic motivations to discover novel anticancer therapeutics. Accordingly, remedial procedures that emphasize focusing on CSCs and their micro environmental niche are insufficient for conventional malignant growth treatments to eradicate the CSCs that, in any case, bring about therapy resistance. Mutual utilization of traditional therapies with CSC- specific agents may offer a promising technique for enduring cancer treatment as well as remedy.
