Nectin-4 (Nectin cell adhesion molecule 4), a type I transmembrane cell adhesion protein, was demonstrated to be overexpressed in a variety of tumors, making it an attractive antigen for targeted therapies such as antibody-drug conjugates (ADCs). Of great note, the US Food and Drug Administration (FDA)-approval of the first Nectin-4-directed ADC, enfortumab vedotin (EV), in urothelial cancer (UC) not only introduced Nectin-4 as a clinically validated and reliable target antigen but also confirmed the evolving role of Nectin-4-directed ADCs as novel and promising cancer therapeutics. In addition to EV, there have been or are currently being seven and eleven Nectin-4-directed ADCs, respectively, in various stages of clinical trials and preclinical development, offering a promising future for the treatment of Nectin-4-positive cancer patients.
View Article and Find Full Text PDFBackground: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal system. So far, no treatment has been identified that can completely cure IBD. Lactobacillus brevis is hypothesized to be beneficial in preventing inflammation.
View Article and Find Full Text PDFInflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal (GI) system that includes two groups, Crohn's disease (CD) and ulcerative colitis (UC). To cope with these two classes of IBD, the investigation of pathogenic mechanisms and the discovery of new diagnostic and therapeutic approaches are crucial. Long non-coding RNAs (lncRNAs) which are non-coding RNAs with a length of longer than 200 nucleotides have indicated significant association with the pathology of IBD and strong potential to be used as accurate biomarkers in diagnosing and predicting responses to the IBD treatment.
View Article and Find Full Text PDFBackground: The coronavirus pandemic that started in 2019 has caused the highest mortality and morbidity rates worldwide. Data on the role of long non-coding RNAs (lncRNAs) in coronavirus disease 2019 (COVID-19) is scarce. We aimed to elucidate the relationship of three important lncRNAs in the inflammatory states, H19, taurine upregulated gene 1 (TUG1), and colorectal neoplasia differentially expressed (CRNDE) with key factors in inflammation and fibrosis induction including signal transducer and activator of transcription3 (STAT3), alpha smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in COVID-19 patients with moderate to severe symptoms.
View Article and Find Full Text PDFThe cell-surface receptor tyrosine kinase c-mesenchymal-epithelial transition factor (c-Met) is overexpressed in a wide range of solid tumors, making it an appropriate target antigen for the development of anticancer therapeutics. Various antitumor c-Met-targeting therapies (including monoclonal antibodies [mAbs] and tyrosine kinases) have been developed for the treatment of c-Met-overexpressing tumors, most of which have so far failed to enter the clinic because of their efficacy and complications. Antibody-drug conjugates (ADCs), a new emerging class of cancer therapeutic agents that harness the target specificity of mAbs to deliver highly potent small molecules to the tumor with the minimal damage to normal cells, could be an attractive therapeutic approach to circumvent these limitations in patients with c-Met-overexpressing tumors.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) ranks among the most prevalent cancers and accounts for a significant proportion of cancer-associated deaths worldwide. This disease, marked by multifaceted etiology, often poses diagnostic challenges. Finding a reliable and non-invasive diagnostic method seems to be necessary.
View Article and Find Full Text PDFIndividuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms.
View Article and Find Full Text PDFNowadays, anti-TNF therapy remarkably improves the medical management of ulcerative colitis (UC), but approximately 40 % of patients do not respond to this treatment. In this study, we used 79 anti-TNF-naive patients with moderate-to-severe UC from four cohorts to discover alternative therapeutic targets and develop a personalized medicine approach that can diagnose UC non-responders (UCN) prior to receiving anti-TNF therapy. To this end, two microarray data series were integrated to create a discovery cohort with 35 UC samples.
View Article and Find Full Text PDFBackground: Inflammatory bowel disease (IBD) is a complex gastrointestinal disease with 2 main subtypes of Crohn's disease (CD) and ulcerative colitis (UC), whose diagnosis mainly depends on the medical history, clinical symptoms, endoscopic, histologic, radiological, and serological findings. Extracellular vesicles (EVs) are now considered an additional mechanism for intercellular communication, allowing cells to exchange biomolecules. Long noncoding RNAs (lncRNAs) that are enriched in EVs have been defined as an ideal diagnostic biomarker for diseases.
View Article and Find Full Text PDFAntibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity of a monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules to targeted cancer cells, leading to an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after the approval and tremendous success of trastuzumab emtansine and trastuzumab deruxtecan, representing a turning point in both HER2-positive breast cancer treatment and ADC technology. Additionally and importantly, a total of 29 ADC candidates are now being investigated in different stages of clinical development for the treatment of HER2-positive breast cancer.
View Article and Find Full Text PDFBackground: Autophagy is an important part of pathogenesis of IBD. Thiopurines such as azathioprine (AZA) are approved drugs for clinical practices in IBD patients. Besides, as an escape strategy, Toxoplasma gondii can use the mTORC1 complex to inactivate autophagy.
View Article and Find Full Text PDFA large number of people worldwide suffer from visual impairment. However, most available therapies rely on impeding the development of a particular eye disorder. Therefore, there is an increasing demand for effective alternative treatments, specifically regenerative therapies.
View Article and Find Full Text PDFConsidering the significant limitations of conventional 2D cell cultures and tissue in vitro models, creating intestinal organoids has burgeoned as an ideal option to recapitulate the heterogeneity of the native intestinal epithelium. Intestinal organoids can be developed from either tissue-resident adult stem cells (ADSs) or pluripotent stem cells (PSCs) in both forms induced PSCs and embryonic stem cells. Here, we review current advances in the development of intestinal organoids that have led to a better recapitulation of the complexity, physiology, morphology, function, and microenvironment of the intestine.
View Article and Find Full Text PDFDespite the extensive body of research, understanding the exact molecular mechanisms governing inflammatory bowel diseases (IBDs) still demands further investigation. Transforming growth factor-β1 (TGF-β1) signaling possesses a multifacial effect on a broad range of context-dependent cellular responses. However, long-term TGF-β1 activity may trigger epithelial-mesenchymal transition (EMT), followed by fibrosis.
View Article and Find Full Text PDFThe activation of hepatic stellate cells is the primary function of facilitating liver fibrosis. Interfering with the coordinators of different signaling pathways in activated hepatic stellate cells (aHSCs) could be a potential approach in ameliorating liver fibrosis. Regarding the illustrated anti-fibrotic effect of imatinib in liver fibrosis, we investigated the imatinib's potential role in inhibiting HSC activation through miR-124 and its interference with the STAT3/hepatic leukemia factor (HLF)/IL-6 circuit.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
March 2023
Background: Efficient differentiation of mesenchymal stem cells (MSCs) into a desired cell lineage remains challenging in cell-based therapy and regenerative medicine. Numerous efforts have been made to efficiently promote differentiation of MSCs into osteoblast lineage. Accordingly, epigenetic signatures emerge as a key conductor of cell differentiation.
View Article and Find Full Text PDFBackground: The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients.
Method: The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls.
Background: Regardless of improvements in controlling the COVID-19 pandemic, the lack of comprehensive insight into SARS-COV-2 pathogenesis is still a sophisticated challenge. In order to deal with this challenge, we utilized advanced bioinformatics and machine learning algorithms to reveal more characteristics of SARS-COV-2 pathogenesis and introduce novel host response-based diagnostic biomarker panels.
Methods: In the present study, eight published RNA-Seq datasets related to whole-blood (WB) and nasopharyngeal (NP) swab samples of patients with COVID-19, other viral and non-viral acute respiratory illnesses (ARIs), and healthy controls (HCs) were integrated.
Inflammatory bowel disease (IBD) is a debilitating and incurable inflammatory disorder. Despite its increasing prevalence, the underlying pathogenic mechanisms of IBD have not been fully clarified. In addition to the regulatory role of Sonic Hedgehog (SHH) signaling in the maintenance of gut homeostasis, its involvement in development of inflammatory disorders and organ fibrosis has also been reported.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the leading cause of dementia that has remained a major medical, sociocultural and economical challenge globally. Previously developed treatments like anticholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor (NMDAR) antagonists only provide short-term symptomatic improvement and do not prevent progression. Repeated setbacks and failures over the past 25 years in AD clinical trials have hindered efforts to develop effective AD treatments.
View Article and Find Full Text PDFGender-specific phenotypes of the heart were reported with respect to both physiology and pathology. While most differences were associated with the sex hormones, differential expression of genes received special attention, particularly X-Y chromosomes' genes. Here, we compared cardiogenesis by gene expression analysis of lineage specific markers and X-Y chromosomes' genes, during differentiation of XY and XX human embryonic stem cells (hESC), in a hormone-free setup.
View Article and Find Full Text PDFExpert Rev Mol Diagn
September 2021
Introduction: Extracellular vesicles (EVs) play an important role in cell-cell communication and regulation of various cellular functions under physiological and pathophysiological conditions through transferring their cargo to recipient cells. Molecular constituents of EVs are a fingerprinting profile of secreting cells which can be used as promising prognostic, diagnostic, and drug-response biomarkers in clinical settings.
Areas Covered: The present study provides a brief introduction about the biology of EVs and reviews methodologies used for EV isolation and characterization as well as high-throughput strategies to analyze EV contents.
Viruses are obligatory intracellular parasites that use cell proteins to take the control of the cell functions in order to accomplish their life cycle. Studying the viral-host interactions would increase our knowledge of the viral biology and mechanisms of pathogenesis. Studies on pathogenesis mechanisms of lyssaviruses, which are the causative agents of rabies, have revealed some important host protein partners for viral proteins, especially for most studied species, i.
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