14 research outputs found
Types of Cell Death from a Molecular Perspective
No full textThe former conventional belief was that cell death resulted from either apoptosis or necrosis; however, in recent years, different pathways through which a cell can undergo cell death have been discovered. Various types of cell death are distinguished by specific morphological alterations in the cell’s structure, coupled with numerous biological activation processes. Various diseases, such as cancers, can occur due to the accumulation of damaged cells in the body caused by the dysregulation and failure of cell death. Thus, comprehending these cell death pathways is crucial for formulating effective therapeutic strategies. We focused on providing a comprehensive overview of the existing literature pertaining to various forms of cell death, encompassing apoptosis, anoikis, pyroptosis, NETosis, ferroptosis, autophagy, entosis, methuosis, paraptosis, mitoptosis, parthanatos, necroptosis, and necrosis
Mitigating Diabetic Cardiomyopathy: The Synergistic Potential of Sea Buckthorn and Metformin Explored via Bioinformatics and Chemoinformatics
No full textDiabetic cardiomyopathy (DCM), a critical complication of type 2 diabetes mellitus (T2DM), is marked by metabolic dysfunction, oxidative stress, and chronic inflammation, ultimately progressing to heart failure. This study investigated the synergistic therapeutic potential of Hippophae rhamnoides L. (sea buckthorn, SBU) extract and metformin in a mouse model of T2DM-induced DCM. T2DM was induced using a 45% high-fat-AGEs-enriched diet, followed by treatment with SBU, metformin, or their combination. Treatment effects were monitored through bioinformatic analysis, chemoinformatic prediction, behavioral testing, biochemical assays, histopathological evaluations and gene expression profiles. Based on bioinformatic analysis, we identified key hub genes involved in the diabetic cardiomyopathy including SERPINE1, NRG1, MYH11, PTH, NR4A2, NRF2, PGC1α, GPX4, ATF1, ASCL2, NOX1, NLRP3, CCK8, COX2, CCL2, PTGS2, EGFR, and oncostatin, which are pivotal in modulating the ferroptosis pathway. Furthermore, the expression of long non-coding RNAs (lncRNAs) NEAT1 and MALAT1, critical regulators of inflammation and cell death, was effectively downregulated, correlating with decreased levels of the pro-inflammatory marker oncostatin. The combined therapy significantly improved glucose regulation, reduced systemic inflammation and protected the heart from oxidative damage. Histopathological analysis revealed notable reductions in cardiac necrosis and fibrosis. Particularly, the combination therapy of SBU and metformin demonstrated a synergistic effect, surpassing the benefits of individual treatments in preventing cardiac damage. These findings highlight the potential of integrating SBU with metformin as a novel therapeutic strategy for managing DCM by targeting both metabolic and ferroptosis-related pathways. This dual intervention opens promising avenues for future clinical applications in diabetic heart disease management, offering a comprehensive approach to mitigating the progression of DCM
Sparassis latifolia and exercise training as complementary medicine mitigated the 5-fluorouracil potent side effects in mice with colorectal cancer: bioinformatics approaches, novel monitoring pathological metrics, screening signatures, and innovative management tactic
No full textAbstract Background Prompt identification and assessment of the disease are essential for reducing the death rate associated with colorectal cancer (COL). Identifying specific causal or sensitive components, such as coding RNA (cRNA) and non-coding RNAs (ncRNAs), may greatly aid in the early detection of colorectal cancer. Methods For this purpose, we gave natural chemicals obtained from Sparassis latifolia (SLPs) either alone or in conjunction with chemotherapy (5-Fluorouracil to a mouse colorectal tumor model induced by AOM-DSS. The transcription profile of non-coding RNAs (ncRNAs) and their target hub genes was evaluated using qPCR Real-Time, and ELISA techniques. Results MSX2, MMP7, ITIH4, and COL1A2 were identified as factors in inflammation and oxidative stress, leading to the development of COL. The hub genes listed, upstream regulatory factors such as lncRNA PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p have been discovered as biomarkers for prognosis and diagnosis of COL. The SLPs and exercise, effectively decreased the size and quantity of tumors. Conclusions This effect may be attributed to the modulation of gene expression levels, including MSX2, MMP7, ITIH4, COL1A2, PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p. Ultimately, SLPs and exercise have the capacity to be regarded as complementing and enhancing chemotherapy treatments, owing to their efficacious components
Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
No full textChemotherapy-related cognitive impairment (CRCI), is a well-recognized phenomenon in cancer patients who have undergone chemotherapy but the exact molecular mechanisms underpinning CRCI remain elusive. Symptoms reported by people with CRCI resemble those experienced by people with age-related neurodegenerative disorders (ARNDDs), yet no clear connection between CRCI and ARNDDs has been reported to date. The existence of shared mechanisms between these conditions offers opportunities for repurposing drugs already approved for the treatment of ARNDDs to improve symptoms of CRCI. Given that there is no available microarray or RNA-Seq data from the brains of people who have experienced CRCI, we investigated to what extent brain gene expression perturbations from validated rodent models of CRCI induced by chemotherapy compared with validated rodent models of Alzheimer’s disease and Parkinson’s disease. We utilized multiple bioinformatic analyses, including functional enrichment, protein-protein interaction network analyses, gene ontology analyses and identification of hub genes to reveal connections between comparable gene expression perturbations observed in these conditions. Collectively 165 genes overlapped between CRCI and Parkinson’s disease and/or Alzheimer’s disease, and 15 overlapped between all three conditions. The joint genes between Alzheimer’s disease, Parkinson’s disease and CRCI demonstrate an average of 83.65% nucleotide sequence similarity to human orthologues. Gene ontology and pathway enrichment analyses suggest mechanisms involved in neural activity and inflammatory response as the key components of the studied neuropathological conditions. Accordingly, genes in which expression was comparably affected in all three condition models could be attributed to neuroinflammation, cell cycle arrest, and changes in physiological neural activity
The Importance of SNPs at miRNA Binding Sites as Biomarkers of Gastric and Colorectal Cancers: A Systematic Review
No full textDysregulated mRNA–miRNA profiles might have the prospective to be used for early diagnosis of gastrointestinal cancers, estimating survival, and predicting response to treatment. Here, a novel biomarker based on miRNAs binding to mRNAs in single nucleotide polymorphism (SNP) sites related to gastrointestinal cancers is introduced that could act as an early diagnosis. The electronic databases used for the recruiting published articles included EMBASE, SCOPUS, Web of Science, and PubMed, based on MESH keywords and PRISMA methodology. Based on the considered criteria, different experimental articles were reviewed, during which 15 studies with the desired criteria were collected. Accordingly, novel biomarkers in prediction, early prognosis, and diagnosis of gastrointestinal cancers were highlighted. Moreover, it was found that 20 SNP sites and 16 miRNAs were involved in gastrointestinal cancers, with altered expression patterns associated with clinicopathological and demographic data. The results of this systematic study revealed that SNPs could affect the binding of miRNAs in the SNP sites that might play a principal role in the progression, invasion, and susceptibility of gastrointestinal cancers. In addition, it was found that the profiles of SNPs and miRNAs could serve as a convenient approach for the prognosis and diagnosis of gastric and colorectal cancers
PPARγ/Pgc-1α-Fndc5 pathway up-regulation in gastrocnemius and heart muscle of exercised, branched chain amino acid diet fed mice
No full textAbstract Background Previous studies have revealed the inductive effect of branched-chain amino acids (BCAAs) catabolism on fatty acid oxidation and metabolism, especially in muscle cells. In the present investigation, we have attempted to address whether a combination of BCAAs supplement consumption with aerobic exercise could elaborate the expression of PPARγ, Pgc-1α and Fndc5 genes in gastrocnemius muscle and heart tissue of male C57BL/6 mice. Methods Thirty-six young male mice with an average weight of 18 ± 2 g were selected. Mice were randomly assigned to 6 groups: 20 mg/mL of BCAAs consumption with simultaneous exercise-training, 60 mg/mL of BCAAs consumption with simultaneous exercise-training, exercise-trained with no BCAAs consumption group, 20 mg/mL BCAAs without exercise-training, 60 mg/mL BCAAs without exercise-training, and untrained mice without BCAAs consumption. Results The findings showed a combination of 20 mg/mL BCAAs with aerobic exercise significantly increased Fndc5, PPARγ, Pgc-1α gene expression in skeletal muscles although, circulating Irisin levels remained unchanged (p < 0.05). Interestingly, plasma urea and lactate levels were significantly increased in 60 mg/mL BCAAs administrated mice which performed exercised (p < 0.05). Two-way analysis of variance (ANOVA) was used to examine significant difference between groups and sedentary group. Conclusions Results showed inductive effect of 20 mg/mL BCAAs on expression levels of Fndc5, PPARγ, Pgc-1α in gastrocnemius muscle similar with counterparts in heart tissue. Of note, higher serum irisin levels were detected after 20 mg/mL BCAAs supplementation coincided with the exercise. Graphical abstract An Overview on supplemantaion of branched chain amoinoacids on metablism of skeletal muscle and hear
The molecular perspective on the melanoma and genome engineering of T-cells in targeting therapy
No full textMelanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma
Correction to: A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice (Nutrition & Metabolism, (2021), 18, 1, (14), 10.1186/s12986-021-00543-6)
No full textFollowing the publication of the original article 1, the authors identified an error in the funding note. Incorrect funding note: A part of this research was funded partially by NIMAD (National Institute for Medical Research Development) no. 971130. © 2021, The Author(s)
agonist, pioglitazone, reversed Dox‐induced cardiotoxicity through mediating of miR‐130a downregulation in C57BL/6 mice
No full textDoxorubicin (Dox) is an antitumor agent widely used in cancer therapy, with notable side effects of cardiac toxicity. Peroxisome proliferator-activated receptor gamma (PPAR gamma), is a transcriptional factor with antiapoptotic and anti-inflammatory properties. Recently we indicated that cardiac toxicity of Dox was due to upregulation of miR-130a and further suppressive effect on cardiac Ppar gamma in vitro. In this study, we extended our proposed hypothesis in vivo. To achieve this, pioglitazone (Pio) and GW9662 were used as the specific agonist and antagonist of Ppar gamma to treat Dox-injected mice. Heart function, apoptosis, and inflammation in heart tissue were studied. Pretreatment of Dox-injected mice with Pio resulted in elevated expression of Ppar gamma and suppression of miR-130a. However, GW9662 pretreatment was unable to increase miR-130a expression. Pio pretreatment led to partially cardiac toxicity limitation of Dox whereas GW9662 caused heart damage. Finally, our observation determined that activation of Ppar gamma was not adequate to reverse the Dox-induced toxicity completely
Additional file 1: of PPARγ/Pgc-1α-Fndc5 pathway up-regulation in gastrocnemius and heart muscle of exercised, branched chain amino acid diet fed mice
No full textFigure S1. Comparative study on amino acid content of proteins in human and mouse. As shown, the assessed proteins were the same as were obtained by STRING analysis (Fig. 2). Dark color indicates more homology in amino acid residues and bright red color represents more dissimilarity between human and mouse proteins. Of interest most similarity was obtained for PPARγ, and FNDC5 between mouse and human. (JPG 86 kb
