Coronary heart disease (CHD) is a global health concern, and its molecular origin is not fully elucidated. Dysregulation of ncRNAs has been linked to many metabolic and infectious diseases. This study aimed to explore the role of circRNAs in the pathogenesis of CHD and predicted a candidate circRNA that could be targeted for therapeutic approaches to the disease. circRNAs associated with CHD were identified and CHD gene expression profiles were obtained, and analyzed with GEO2R. In addition, differentially expressed miRNA target genes (miR-DEGs) were identified and subjected to functional enrichment analysis. Networks of circRNA/miRNA/mRNA and the miRNA/affected pathways were constructed. Furthermore, a miRNA/mRNA homology study was performed. We identified that hsa_circ_0126672 was strongly associated with the CHD pathology by competing for endogenous RNA (ceRNA) mechanisms. hsa_circ_0126672 characteristically sponges miR-145-5p, miR-186-5p, miR-548c-3p, miR-7-5p, miR-495-3p, miR-203a-3p, and miR-21. Up-regulation of has_circ_0126672 affected various CHD-related cellular functions, such as atherosclerosis, JAK/STAT, and Apelin signaling pathways. Our results also revealed a perfect and stable interaction for the hybrid of miR-145-5p with NOS1 and RPS6KB1. Finally, miR-145-5p had the highest degree of interaction with the validated small molecules. Henchashsa_circ_0126672 and target miRNAs, notably miR-145-5p, could be good candidates for the diagnosis and therapeutic approaches to CHD.
Cardiovascular disease (CVD), a broad-spectrum term comprising coronary artery disease, stroke, hypertension, and heart failure, presents as one of the most significant strains on global healthcare systems. Coronary artery disease, caused by atherosclerosis, has various modifiable risk factors such as dietary changes and exercise. Since these risk factors are found to be linked to oxidative stress and inflammations, the dietary supplementation with vitamins’ role in treating and preventing the diseases has been of much debate. With various vitamins having anti-inflammatory and antioxidative properties, studies have explored their correlation with cardiovascular health. Therefore, this narrative review explores and evaluates the benefits and risks of all vitamin supplementations in patients with CVD and provides future recommendations.
Abstract Human amniotic epithelial cells (hAECs) are non-immunogenic epithelial cells that can develop into cells of all three germline lineages. However, a refined clinically reliable method is required to optimize the preparation and banking procedures of hAECs for their successful translation into clinical studies. With the goal of establishing standardized clinically applicable hAECs cultured cells, we described the use of a powerful epithelial cell culture technique, termed C onditionally R eprogrammed Cells (CRC) for ex vivo expansion of hAECs. The well-established CRC culture method uses a Rho kinase inhibitor (Y-27632) and J2 mouse fibroblast feeder cells to drive the indefinite proliferation of all known epithelial cell types. In this study, we used an optimized CRC protocol to successfully culture hAECs in a CRC medium supplemented with xenogen-free human serum. We established that hAECs thrive under the CRC conditions for over 5 passages while still expressing pluripotent stem markers (OCT-4, SOX-2 and NANOG) and non-immunogenic markers (CD80, CD86 and HLA-G) suggesting that even late-passage hAECs retain their privileged phenotype. The hAECs-CRC cells were infected with a puromycin-selectable lentivirus expressing luciferase and GFP (green fluorescent protein) and stably selected with puromycin. The hAECs expressing GFP were injected subcutaneously into the flanks of Athymic and C57BL6 mice to check the tolerability and stability of cells against the immune system. Chemiluminescence imaging confirmed the presence and viability of cells at days 2, 5, and 42 without acute inflammation or any tumor formation. Collectively, these data indicate that the CRC approach offers a novel solution to expanding hAECs in humanized conditions for future clinical uses, while retaining their primary phenotype. Graphical abstract
// Lucas Tricoli 1, 4 , Aisha Naeem 1 , Erika Parasido 1 , John P. Mikhaiel 1 , Muhammad Umer Choudhry 1 , Deborah L. Berry 1 , Iman A. Abdelgawad 2 , Richard J. Lee 3 , Adam S. Feldman 3 , Chukwuemeka Ihemelandu 1 , Maria Avantaggiati 1 , Deepak Kumar 4 , Stephen Byers 1 , Rosa Gallagher 5 , Julia Wulfkuhle 5 , Emanuel Petricoin 5 , Olga Rodriguez 1, 6 and Chris Albanese 1, 6 1 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA 2 National Cancer Institute of Egypt, Cairo, Egypt 3 Massachusetts General Hospital Cancer Center, Boston, MA, USA 4 Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA 5 Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA 6 Preclinical Imaging Research Laboratory, Georgetown University Medical Center, Washington, DC, USA Correspondence to: Chris Albanese, email: albanese@georgetown.edu Keywords: prostate; cancer; primary tissue; reprogrammed cells; androgen Received: October 26, 2017 Accepted: November 02, 2017 Published: December 18, 2017 ABSTRACT The inability to propagate human prostate epithelial cells indefinitely has historically presented a serious impediment to prostate cancer research. The conditionally reprogrammed cell (CRC) approach uses the combination of irradiated J2 mouse fibroblasts and a Rho kinase inhibitor such as Y27632 to support the continuous culture of cells derived from most epithelial tissues, including the prostate. Due to their rapid establishment and overall ease of use, CRCs are now widely used in a variety of basic and preclinical settings. In addition, CRCs were successfully used to clinically treat respiratory papillomatosis. Although both normal and tumor-derived prostate CRCs have been used to study the basic biology of prostate cancer and to test new therapies, certain limitations exist. We have previously reported that prostate CRCs form functional prostate glands when implanted under the mouse renal capsule. However in conventional culture, the prostate CRCs exist in an adult stem-like, transient amplifying state and consequently do not adequately recapitulate several important features of a differentiated prostate epithelium. To address these limitations, we previously described a transwell dish-based model that supported the culturing of prostate CRCs and the collection of cells and cell extracts for molecular and genetic analyses. Using normal and tumor-derived prostate CRCs, we describe the combined effects of the multi-dimensional transwell platform and defined culture media on prostate cellular proliferation, differentiation and signaling.
The regulation of genes is crucial for maintaining a healthy intracellular environment, and any dysregulation of gene expression leads to several pathological complications. It is known that many diseases, including kidney diseases, are regulated by miRNAs. However, the data on the use of miRNAs as biomarkers for the diagnosis and treatment of chronic kidney disease (CKD) are not conclusive. The purpose of this study was to elucidate the potential of miRNAs as an efficient biomarker for the detection and treatment of CKD at its early stages. Gene expression profiling data were acquired from the Gene Expression Omnibus (GEO) and differentially expressed genes (DEGs) were identified. miRNAs directly associated with CKD were obtained from an extensive literature search. Network illustration of miRNAs and their projected target differentially expressed genes (tDEGs) was accomplished, followed by functional enrichment analysis. hsa-miR-1-3p, hsa-miR-206, hsa-miR-494 and hsa-miR-577 exhibited a strong association with CKD through the regulation of genes involved in signal transduction, cell proliferation, the regulation of transcription and apoptotic process. All these miRNAs have shown significant contributions to the inflammatory response and the processes which eventually lead to the pathogenesis of CKD. The in silico approach used in this research represents a comprehensive analysis of identified miRNAs and their target genes for the identification of molecular markers of disease processes. The outcomes of the study recommend further efforts for developing miRNA biomarkers set for the early diagnosis of CKD.
Artificial Intelligence (AI) performs human intelligence-dependant tasks using tools such as Machine Learning, and its subtype Deep Learning. AI has incorporated itself in the field of cardiovascular medicine, and increasingly employed to revolutionize diagnosis, treatment, risk prediction, clinical care, and drug discovery. Heart failure has a high prevalence, and mortality rate following hospitalization being 10.4% at 30-days, 22% at 1-year, and 42.3% at 5-years. Early detection of heart failure is of vital importance in shaping the medical, and surgical interventions specific to HF patients. This has been accomplished with the advent of Neural Network (NN) model, the accuracy of which has proven to be 85%. AI can be of tremendous help in analyzing raw image data from cardiac imaging techniques (such as echocardiography, computed tomography, cardiac MRI amongst others) and electrocardiogram recordings through incorporation of an algorithm. The use of decision trees by Rough Sets (RS), and logistic regression (LR) methods utilized to construct decision-making model to diagnose congestive heart failure, and role of AI in early detection of future mortality and destabilization episodes has played a vital role in optimizing cardiovascular disease outcomes. The review highlights the major achievements of AI in recent years that has radically changed nearly all areas of HF prevention, diagnosis, and management.
Objective: To assess the practice of ordering unnecessary laboratory investigations by primary surgical teams. Method: The clinical audit was conducted from December 17, 2022, to January 15, 2023, at the Civil Hospital, Karachi, and comprised primary surgeons working in different surgical units who ordered laboratory investigations for patients as a part of preoperative assessment. Data was collected using a self-administered questionnaire. Data was analysed using SPSS 20. Results: Of the 280 surgeons approached, 249(89%) responded. The units covered were General surgery 96(38.5%), Gynaecology 74(29.7%), Neurosurgery 5(2.0%), Ear, Nose and Throat 19(7.6%), Plastic surgery 15(6.02%), Paediatric surgery 13(5.2%), Vascular surgery 8(3.21%), Oromaxilofacial 9(3.61%), Opthalmology 6(2.4%), and Orthopaedics 4(1.60%).As part of baseline investigations, 244(98%) surgeons ordered complete blood count, 173(69.5%) ordered urea and creatinine, 229(92%) ordered viral markers, 197(78.7%) ordered fasting and random blood glucose, and 178(71.5%) focussed on cardiac fitness. Conclusion: There was a found a need for standard protocols for pre-surgery evaluation so that unnecessary investigations may be avoided. Key Words: Preoperative, Investigation, Guidelines, Assessment, Audit.
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and, very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel (n-PTX) has been added to the arsenal of first-line therapies, and the combination of gemcitabine and n-PTX has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying n-PTX resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naïve patients with PDAC. To study the mechanisms of primary drug resistance, nab-paclitaxel–resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified <i>in vivo</i>, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of <i>c-MYC</i> in the n-PTX-R cells. Depletion of c-MYC restored n-PTX sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small-molecule activator of protein phosphatase 2a.</p>Implications:<p>The strategies we have devised, including the patient-derived primary cells and the unique, drug-resistant isogenic cells, are rapid and easily applied <i>in vitro</i> and <i>in vivo</i> platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis.</p></div>
The successful translation of mesenchymal stem cells (MSCs) from bench to bedside is predicated upon their regenerative capabilities and immunomodulatory potential. Many challenges still exist in making MSCs a viable and cost-effective therapeutic option, due in part to the challenges of sourcing MSCs from adult tissues and inconsistencies in the characterization of MSCs. In many cases, adult MSC collection is an invasive procedure, and ethical concerns and age-related heterogeneity further complicate obtaining adult tissue derived MSCs at the scales needed for clinical applications. Alternative adult sources, such as post-partum associated tissues, offer distinct advantages to overcome these challenges. However, successful therapeutic applications rely on the efficient ex-vivo expansion of the stem cells while avoiding any culture-related phenotypic alterations, which requires optimized and standardized isolation, culture, and cell preservation methods. In this review, we have compared the isolation and culture methods for MSCs originating from the human amniotic membrane (hAMSCs) of the placenta to identify the elements that support the extended subculture potential of hAMSCs without compromising their immune-privileged, pluripotent regenerative potential.Abbreviations: AM: Human amniotic membrane; ASCs: Adipose tissue-derived stem cells; BM-MSCs: Bone marrow-mesenchymal stem cells; DMEM: Dulbecco's modified eagle medium; DT: Doubling time; EMEM: Eagle's modified essential medium; ESCM: Embryonic stem cell markers; ESCs: Embryonic stem cells; hAECs: Human amniotic epithelial cells; hAMSCs: Human amniotic mesenchymal stem cells; HLA: Human leukocyte antigen; HM: Hematopoietic markers; IM: Immunogenicity markers; MHC: Major histocompatibility complex; MSCs: Mesenchymal stem cells; MCSM: Mesenchymal cell surface markers; Nanog: NANOG homeobox; Oct: Octamer binding transcription factor 4; P: Passage; PM: Pluripotency markers; STRO-1: Stromal precursor antigen-1; SCP: Subculture potential; Sox-2: Sry-related HMG box gene 2; SSEA-4: Stage-specific embryonic antigen; TRA: Tumor rejection antigen
Non-coding RNAs (ncRNAs) participate in the regulation of several cellular processes including transcription, RNA processing and genome rearrangement. The aberrant expression of ncRNAs is associated with several pathological conditions. In this review, we focused on recent information to elucidate the role of various regulatory ncRNAs i.e., micro RNAs (miRNAs), circular RNAs (circRNAs) and long-chain non-coding RNAs (lncRNAs), in metabolic diseases, e.g., obesity, diabetes mellitus (DM), cardiovascular diseases (CVD) and metabolic syndrome (MetS). The mechanisms by which ncRNAs participated in disease pathophysiology were also highlighted. miRNAs regulate the expression of genes at transcriptional and translational levels. circRNAs modulate the regulation of gene expression via miRNA sponging activity, interacting with RNA binding protein and polymerase II transcription regulation. lncRNAs regulate the expression of genes by acting as a protein decoy, miRNA sponging, miRNA host gene, binding to miRNA response elements (MRE) and the recruitment of transcriptional element or chromatin modifiers. We examined the role of ncRNAs in the disease pathogenesis and their potential role as molecular markers for diagnosis, prognosis and therapeutic targets. We showed the involvement of ncRNAs in the onset of obesity and its progression to MetS and CVD. miRNA-192, miRNA-122, and miRNA-221 were dysregulated in all these metabolic diseases. Other ncRNAs, implicated in at least three diseases include miRNA-15a, miRNA-26, miRNA-27a, miRNA-320, and miRNA-375. Dysregulation of ncRNAs increased the risk of development of DM and MetS and its progression to CVD in obese individuals. Hence, these molecules are potential targets to arrest or delay the progression of metabolic diseases.
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