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The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.
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Gastric cancer (GC) is a prominent public health issue and ranks as the third most prevalent cause of cancer-related mortality on a global scale. The role of long non-coding RNAs (lncRNAs) in cancer is not yet fully understood, particularly in relation to GC development. The objective of this study was to examine the expression levels of lncRNAs in GC tissues using a bioinformatics-based ranking approach. A bioinformatics methodology was employed to prioritize lncRNAs that are hypothesized to play a role in GC tumorigenesis. Moreover, a selection was made for experimental validation of the highest-ranked lncRNAs, which include HCG18, OIP5-AS1, FGD5-AS1, and NORAD. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to confirm the results obtained from bioinformatics analysis in a total of 35 GC samples and their corresponding adjacent non-tumoral samples. Receiver operating characteristic (ROC) curves and the corresponding area under the ROC curve (AUC) were utilized to evaluate the diagnostic efficacy of the lncRNAs. The bioinformatics analysis revealed that the lncRNA HCG18 is the highest-ranked lncRNA associated with GC. Furthermore, the expression levels of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were found to be significantly elevated in GC samples when compared to adjacent non-tumoral samples. The calculated values for the AUC of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were 0.80, 0.74, 0.73, and 0.71, respectively. The results of the study indicate that the lncRNAs HCG18, OIP5-AS1, FGD5-AS1, and NORAD may play a role in the development of GC. Additionally, the present study revealed that utilizing bioinformatic techniques can prove to be a highly effective strategy in identifying potential lncRNAs pertinent to the progression of GC.
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INTRODUCTION: The hepatitis B virus (HBV) continues to be a leading cause of morbidity and mortality worldwide. In developing countries, HBV is the most common etiology of those liver diseases such as chronic hepatitis B (CHB), acute hepatitis B (AHB), acute-on-chronic liver failure (ACLF), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). CD8+ T cell exhaustion is a condition of T cell malfunction and reduction that plays a crucial role in the progression of HBV infection. AREAS COVERED: This systematic review attempts to evaluate the main inhibitory mechanisms involved in CD8+ T cell exhaustion, in different clinical phases of HBV infection and relation to disease progression. A systematic search in PubMed, Web of Science, and Scopus was performed to identify articles published in English till October 2022. EXPERT OPINION: According to the numerous conducted studies, we conclude that CD8+ T cell exhaustion commonly occurs in the tumoral and chronic suppressive environment and CHB and HCC patients; furthermore, this phenomenon is less seen in AHB and ACLF patients. The emergence of surficial inhibitory receptors (IRs) on CD8+ T cells is the leading cause of exhaustion, and programmed cell death protein-1 (PD-1) has much importance among the others.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Hepatite B Crônica/terapia , Hepatite B Crônica/patologia , Carcinoma Hepatocelular/terapia , Exaustão das Células T , Neoplasias Hepáticas/terapia , Hepatite B/metabolismo , Hepatite B/patologia , Linfócitos T CD8-Positivos/patologia , Vírus da Hepatite B/fisiologia , ImunoterapiaRESUMO
INTRODUCTION: Colorectal cancer (CRC) is a type of cancer in humans that leads to high mortality and morbidity. CD166 and CD326 are immunoglobulins that are associated with cell migration. These molecules are included in tumorigenesis of CRC and serve a great marker of CRC stem cells. In the present study, we devised a novel chimeric protein including the V1-domain of the CD166 and two epitopes of CD326 to use in diagnostic or therapeutic applications. METHODS: In silico techniques were launched to characterize the properties and structure of the protein. We have predicted physicochemical properties, structures, stability, MHC class I binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. The sequence of chimeric gene was optimized for expression in prokaryotic host using online tools and cloned into pET-28a plasmid. The recombinant pET28a was transformed into the E. coli BL21DE3. Expression of recombinant protein was examined by SDS-PAGE and Western blotting. RESULTS: The designed chimeric protein retained high stability and the same immunogenicity as of the original proteins. Bioinformatics data indicated that the epitopes of the synthetic chimeric protein might induce B-cell- and T-cell-mediated immune responses. Furthermore, a gene was synthesized using the codon bias of a prokaryotic expression system. This synthetic gene expressed a bacterial expression system. The recombinant protein with molecular weights of 27kDa was expressed and confirmed by anti-his Western blot analysis. CONCLUSION: The designed recombinant protein may be useful as a CRC diagnostic tool and for developing a protective vaccine against CRC.
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Antígenos CD/análise , Moléculas de Adesão Celular Neuronais/análise , Neoplasias Colorretais/genética , Simulação por Computador , Molécula de Adesão da Célula Epitelial/análise , Proteínas Fetais/análise , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Antígenos CD/genética , Moléculas de Adesão Celular Neuronais/genética , Clonagem Molecular , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Biologia Computacional , Molécula de Adesão da Célula Epitelial/genética , Proteínas Fetais/genética , Humanos , Engenharia de Proteínas , Proteínas Recombinantes/análise , Proteínas Recombinantes/genéticaRESUMO
ICD-85 (venom derived peptides) has anti-proliferative effect and anti- angiogenesis activity on cancer cells. This study was performed to test the effect of ICD-85, on Human breast adenocarcinoma (MCF-7) and normal Human Dermal Fibroblasts (HDF) cell lines. In this experimental study, Mitochondrial activity, Neutral red uptake, Lactate dehydrogenase (cell necrosis), and cell morphology were assessed under unexposed and ICD-85 exposed conditions. Caspase-9 colorimetric assay kit was used to determine caspase protease activity. Morphological changes in MCF-7 cells on treatment with ICD-85 compared with untreated MCF-7 cells are consistent with characterizing the features of apoptosis such as granulation and cell rounding which finally results in the generation of apoptotic bodies. In contrast, this difference was not observed in normal cells. In MTT assay, ICD-85 induced dose dependent manner cytotoxic effects on MCF-7 cells which were confirmed by neutral red assay. The results showed that inhibitory concentration 50% (IC50) value of ICD-85 for MCF-7 cells at 24 h was 36.45 ± 0.38 µg/mL. However, when HDF cells were exposed to ICD-85, no significant elevation of LDH release were observed at concentrations below 20 µg/mL. The apoptosis-induction of ICD-85 on MCF-7 cell was found to be through activation of caspase-9 which was 13 fold greater than unexposed cell. This study showed that ICD-85 induced apoptosis in MCF-7 cell line through caspase activation and hence it can be considered for further investigation to use ICD-85 as a potential therapy for breast cancer.