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Interferon γ Release Test Combined with Pleural Effusion TB-RNA Detection to Improve the Diagnostic Efficiency of Tuberculous Pleural Effusion
No full textBackground: To investigate the role of tuberculosis infection interferon-γ release assay (TB-IGRA) combined with pleural effusion TB-RNA (tuberculosis RNA detection) detection in the diagnosis of tuberculous pleural effusion. Method: In this observational study, serum TB-IGRA and pleural effusion with TB-RNA were detected in patients with tuberculous and malignant pleural effusion, respectively, and the diagnostic effects of the two groups of patients were compared. Result: The content of pleural globulin in the tuberculous pleural effusion group was higher than that in the malignant pleural effusion group;The difference was significant (t = 2.03, p = 0.04). The serum IFN-γ (interferon-gamma) content in patients who were in the tuberculous pleural effusion group was significantly higher than that in the malignant pleural effusion group;The positive rate of TB-IGRA combined with TB-RNA was 97.5% in the tuberculous pleural effusion group and 14.5% in the malignant pleural effusion group;The diagnostic sensitivity of TB-IGRA was significantly better than that of TB-RNA, and the specificity was significantly lower than that of TB-RNA;The diagnostic sensitivity and specificity of TB-IGRA combined with TB-RNA was considerably higher than that of TB-RNA alone, and these differences were statistically significant (p < 0.05). Conclusions: The sensitivity, specificity, and accuracy of TB-IGRA combined with TB-RNA in diagnosing tuberculous pleural effusion are high, and its application may prevent some missed diagnoses of complicated pleural effusion
Inhibition of CREB1/CTL4 Pathway Diminishes the Viability, and Restrains the Proliferation, Migration and Invasion of Breast Cancer Cells by Improving Aberrant Choline Metabolism
No full textBackground: Abnormal Choline (Cho) metabolism is a hallmark of breast cancer (BC). Since the key role of choline transporter-like protein 4 (CTL4) in Cho transport and acetylcholine (ACh) biosynthesis has been reported, this study aimed to investigate additional role and mechanisms of CTL4 in BC. Methods: CTL4 expressions in BC and cAMP-responsive element (CRE)-binding protein-1 (CREB1)-binding motif were analyzed by bioinformatic analysis. After BC cells were transfected with short hairpin RNA against CTL4 (shCTL4) or CREB1-specific small interfering RNA (siCREB1), the CTL4 and CREB1 expressions in BC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of markers relevant to Cho metabolism were also studied. The binding of CREB1 to the CTL4 promoter was verified by chromatin immunoprecipitation assay. After BC cells were transfected with CTL4 overexpression plasmid or siCREB1, BC cell viability, proliferation, invasion, and migration were assessed by cell counting kit-8, 5ʹ-ethynyl-2ʹ-deoxyuridine (EdU) and Transwell assays. Furthermore, CTL4 protein expression and ACh content in BC cells were determined by western blot assay and high-performance liquid chromatography (HPLC) with enzyme-coupled electrochemical assay. Results: CTL4 was highly expressed in BC and its knockdown diminished cell viability, restrained proliferation, migratory and invasion capabilities, reduced ACh content, and down-regulated the level of markers relevant to Cho metabolism in BC cells (p < 0.01). CREB1 could bind to the CTL4 promoter in BC cells. CREB1 silencing decreased the viability, proliferation, migration, invasiveness, ACh content, and the expression levels of CTL4 and Cho metabolism-relevant markers in BC cells (p < 0.001). Moreover, these aforementioned effects were reversed by CTL4 overexpression (p < 0.001). Conclusions: Inhibition of CREB1-CTL4 cascade attenuated aberrant Cho metabolism, thus restraining the malignant progression of BC cells
FOSL2 Aggravates Renal Injury in Diabetic Nephropathy by Activating NF-κB Signaling Pathway
No full textBackground: Diabetic nephropathy (DN) is one of the complications of diabetes, and may lead to abnormal renal functions. Although many studies confirmed that proteins serve as essential factors in DN progression, the function of Fos-like antigen 2 (FOSL2) in DN has not been properly investigated. The purpose of this study is to explore the regulatory role of FOSL2 in DN progression. Methods: The rats were divided into four groups such as Sham, DN, DN+Adeno-associated virus (AAV)-Scramble, and DN+AAV-shFOSL2 groups. The cells were divided into the control, high glucose (HG), HG+negative control (si-NC), and HG+si-FOSL2 groups. The levels of fasting blood glucose (FBG) and oral glucose tolerance (OGTT) were measured through the glucometer. The levels of glycosylated hemoglobin (HbA1c), serum creatinine (Scr), and blood urea nitrogen (BUN) were measured through the automatic biochemistry analyzer. The damage of renal tissues was evaluated through hematoxylin-eosin (HE) staining. The cell apoptosis was measured through TdT-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry. The mRNA expression was examined through Real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels were determined through enzyme linked immuno sorbent assay (ELISA) and western blot. The cell viability was detected through cell counting kit-8 (CCK-8) assay. Results: In this experiment, the animal model (rats induced by Streptozocin (STZ)) and cell model (Human renal glomerular endothelial cells (HRGEC) induced by HG) were built at first. FOSL2 improved the protein expression and knockdown of FOSL2 improved DN progression by reducing FBG, OGTT, HbA1c, 24 hours (h) urine protein (UP), Scr, and BUN levels (p < 0.001). In addition, FOSL2 suppression improved renal injury and inhibited cell apoptosis in DN rats (p < 0.001). Down-regulation of FOSL2 also reduced the inflammation and oxidative stress in DN rats (p < 0.001). In vitro experiments, FOSL2 inhibition enhanced cell viability (p < 0.001) and retarded cell apoptosis (p < 0.05), as well as reduced the inflammation (p < 0.05) and oxidative stress (p < 0.05) in HRGEC cells induced by HG. It was also identified that FOSL2 inhibition suppressed the activation of nuclear factor kappa-B (NF-κB) pathway in DN (p < 0.001). Conclusions: The findings in this study revealed that FOSL2 aggravated renal injury in DN by activating NF-κB signaling pathway. This discovery might offer a promising biomarker for DN treatment
Structural, Morphological and Dielectric Properties of Ru- and Eu-Co-Doped Strontium Apatite Nanoparticles
No full textBackground: Bone is a dielectric material. Thus, improving the dielectric properties of bioceramics has become an important issue in recent years. In this study, we aimed to investigate the effects of europium (Eu) and ruthenium (Ru) doping on the structural, morphological, and dielectric properties of strontium apatites (SrAp). For this, pure, Eu- and Ru-doped SrAp nanoparticles were synthesized by the hydrothermal method. Methods: Hydrothermal synthesis was carried out at 200 °C for 3 h. The structural and morphological properties of the synthesized SrAp nanoparticles were investigated by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDX) analyses. The dielectric properties of the synthesized nanoparticles were investigated. Results: Eu and Ru additives reduced the XRD peak intensities and broadened the peaks. The characteristic XRD peaks of SrAp were affected by Eu and Ru doping. Doping of Ru and Eu co-doped with Ru shifted the planes below the 2θ values. The synthesized particles are in the nanoscale range and in the form of nanorods. The lengths of the nanorods were shortened and expanded by the addition of Eu and Ru. The closest value to 1.67, which is the stoichiometric ratio of Sr/P, was obtained for the sample that had Eu and Ru co-doped (1.47). The Eu and Ru addition affected the electrical properties of the synthesized nanoparticles. Superior dielectric constants, dielectric losses, and alternative current (AC) conductivities were obtained compared with those for Eu- and Ru-doped pure SrAp samples. Conclusions: The results showed that the dielectric properties of SrAp nanoparticles improved; thus, more studies should be performed. The nanoparticles produced in this study can likely be used as biomaterials in biosensors, biomedical applications, and orthopedic and dental applications
Exosomal miR-320c as a Potential Biomarker of Bronchopulmonary Dysplasia at Early Stage: A Pilot Study
No full textBackground: Bronchopulmonary dysplasia has become one of the most common adverse outcomes in premature infants, however, the pathogenesis remains unanswered. This was a prospective pilot study to investigate potential biomarkers of the development of bronchopulmonary dysplasia, which could help in the understanding and management of this disease. Methods: Exosomes were separated from the sputum samples of bronchopulmonary dysplasia patients at 28 days of life (early group) and the time when bronchopulmonary dysplasia was diagnosed (confirmed group). Exosomal micro-RNA was compared with a control group to find differentially expressed micro-RNA. Results: Microvesicles isolated from sputum samples of three groups were assessed by transmission electron microscopy, particle size analysis, as well as flow cytometry. The shape and size of the isolated vesicles from the three groups all matched the typical appearance of exosomes. The micro vesicles isolated from the sputum samples expressed clusters of differentiation (CD), the exosomal biomarkers strikingly, including CD63, CD9, and CD8. There were 1308 exosomal micro-RNA captured in total, in which, miR-320c (micro-RNA 320c) was significantly upregulated in the patients with bronchopulmonary dysplasia, starting at 28 days of age. Compared with the control group, the p value was 0.0046 in the early group and 0.021 in the confirmed group, respectively. There was no significant difference in the expression of miR-320c between the early and confirmed bronchopulmonary dysplasia groups (p = 0.062). Conclusions: The up-regulation of exosomal micro-RNA 320c may serve as a potential biomarker in the early stage of bronchopulmonary dysplasia
GeneXpert-Based Prevalence of Mycobacterium Tuberculosis and Rifampicin Resistance in Suspected Patients of District Narowal, Pakistan
No full textBackground: Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis (MTB) that affects both humans and animals. It is one of the worlds most widespread serious public health challenges. The present study aimed to check the prevalence of tuberculosis through GeneXpert and association with possible risk factors in suspected tuberculosis positive patients in district Narowal, Pakistan. Methods: A designed questionnaire was filled out to collect data from suspected patients including age, gender, area, marital status, diet, economic status, smoking status, home condition, education, and close contact with tuberculosis (TB) patients. A Lung function test was performed. Statistical analysis was done by applying a chi-square test in SPSS software (version 22) to evaluate the association between GeneXpert and acid-fast staining technique. Results: A total of 500 samples were collected and they were analyzed through auramine rhodamine staining to get efficient results samples were further analyzed to GeneXpert. Out of 500 samples, 195 samples were positive for staining and 282 were positive for GeneXpert from both male and female. The prevalence rate was recorded higher in age groups >50 while a lower prevalence rate was recorded in less than 40 age groups. Rifampicin (RIF) resistance was detected in 63 patients in which males showed high resistance to rifampicin with (52.4%) as compared to females with (47.6%) resistance. Conclusion: The actual prevalence of suspected tuberculosis cases is relatively high, and the GeneXpert MTB/RIF assay is superior to traditional acid fast staining in detecting the disease and identifying rifampicin-resistant patients at the same time, which is an important guideline for the diagnosis and treatment of the disease
Effect of ELFN1 on Epithelial-Mesenchymal Transition and Immune Microenvironment in Colon Adenocarcinoma
No full textBackground: The upregulation of extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) has implications in various malignancies. Conversely, its vital role in colon adenocarcinoma (COAD) is still not clearly defined. This study aimed to uncover the ELFN1 role in the progression and immuno-microenvironment of COAD. Methods: This study investigated the ELFN1 expression in 398 tissues of COAD vs 39 normal tissues from The Cancer Genome Atlas (TCGA), 18 tissues of colorectal cancer vs paired normal tissues of GSE50760, and across pan-cancer types. Then, associations between ELFN1 and prognosis and clinical features were analyzed using the Kaplan–Meier and Cox regression (multivariate) model. Meanwhile, a nomogram was also constructed. The method of gene set enrichment analysis (GSEA) was employed to investigate the pathways related to ELFN1. The data of TCGA-COAD cohort was used to find out the correlations between ELFN1 and immune microenvironment, immunophenoscore (IPS), and tumor mutational burden (TMB). Results: The analysis revealed that ELFN1 levels were significantly high in patients with COAD tissues, involvement of lymph nodes and advanced stages. The higher expression of ELFN1 in patients had the inferior result, and for overall survival (OS), the ELFN1 served as an independent risk predictor. The nomogram showed a good predictive capability in 1-, 3-, and 5-year OS. The result of GSEA exhibited a positive correlation with cancer-related and immunosuppressive pathways, such as myogenesis, epithelial-mesenchymal transition (EMT), angiogenesis, IL6-JAK-STAT3 (Interleukin 6-Janus Kinase 1-Signal Transducer and Activator of Transcription 3) signaling pathway, inflammatory response, and IL2-STAT5 (Interleukin 2-Signal Transducer and Activator Of Transcription 5) pathways by up-regulation of ELFN1. This study focused on exploring the relationship between EMT and ELFN1, as 50% of the total genes were highly significant and positively co-expressed with ELFN1 in this pathway. In addition, an increased ELFN1 was related to a higher Immune/Stromal Score, elevated infiltration levels of macrophages M0 and Tregs, and a lower IPS and TMB. Conclusions: Increased ELFN1 in COAD patients correlated with worse prognosis and may influence the tumor progression by activating EMT and formatting immunosuppressive microenvironment, which may help predict the response to immunotherapy
Antioxidant Profiling and Hepatoprotective Potential of Methanolic Extract of Mucuna pruriens Seeds in Male Albino Rats
No full textBackground: Mucuna pruriens (L.) is a tropical medicinal plant, used in folkloric medicine to treat various ailments. The current research was planned to study the antioxidant and hepatoprotective potential of Mucuna pruriens (M. pruriens) seeds methanolic extract using male albino rats. Methods: For the study, M. pruriens seeds methanolic extract was prepared, and antioxidant potential was determined. The methanolic extract of M. pruriens seeds was evaluated for antioxidant potential through different in vitro antioxidant assays. For hepatoprotective potential, the male albino rats were divided into six groups intoxicated with Carbon Tetrachloride (CCl4) except the normal control group rats. The rats in the test groups were treated by administering different dose concentrations of M. pruriens seeds extract. Liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) as well as serum proteins, were determined using kit methods. Oxidative stress markers such as total antioxidant status (TAS), total oxidant status (TOS), and malondialdehyde (MDA) were also determined. Results: Results showed the significant antioxidant potential of M. pruriens seeds methanolic extract. Significant (p < 0.05) improvements in ALT and AST activities were observed, while ALP activity showed no significant improvement in test group rats treated with M. Pruriens seeds methanolic extract compared to the intoxicated group rats. Significant (p < 0.05) variation in serum total protein, albumin and globulin level was noted in test groups rats treated with M. pruriens seeds extract. Significant (p < 0.05) increase in TAS, while at the same time, a decrease in TOS and lipid peroxidation in test group rats administered with varying doses of M. pruriens seeds methanolic extract compared to the toxic group rats verifies the antioxidant potential of this plant. The structure of hepatocytes was damaged in CCl4 intoxicated rats, with improved histological characteristics of liver tissue in positive control rats administered with Silymarin and in test group rats treated with M. pruriens seeds methanolic extract. Conclusions: The study concluded that the methanolic extract of M. pruriens seeds possess antioxidant activities, ameliorating oxidative stress with potential therapeutic applications as a hepatoprotective agent in folkloric medicine
HBeAg Precursor Proteins Interact with APOBEC3A and Inhibit HBV Replication
No full textBackground: Hepatitis B e antigen (HBeAg) precursor proteins, which share an identical encoding PreC/C open reading frame (PreC/C-ORF) of hepatitis B virus (HBV) core, can inhibit viral replication in vitro. The apolipoprotein B mRNA (messenger ribonucleic acid) editing enzyme catalytic polypeptide 3A (APOBEC3A) can inhibit HBV replication by interacting with the HBV core protein. The aim of the study was to explore whether the HBeAg precursor proteins can regulate HBV replication by interacting with APOBEC3A. Methods: Plasmids harboring the coding sequence of HBeAg precursor proteins (P25 and P22) and APOBEC3A were individually or co-transfected into human hepatoma and embryonic kidney cells. P25, P22, and APOBEC3A expressions were quantified by Western blotting. The co-localization and interaction of P25, P22, and APOBEC3A were determined by confocal microscopy and co-immunoprecipitation (Co-IP). We constructed serial precursor proteins of HBeAg deletion mutants for further Co-IP analysis. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate the levels of HBeAg and HBsAg. HBV replication intermediates from the transfected cells were detected by Southern blotting. Results: P25, P22, and APOBEC3A proteins were successfully expressed in transfected cells, and both P25 and P22 protein co-localization with APOBEC3A protein in the cytoplass. Co-IP with APOBEC3A was mediated by the central region of the HBeAg precursor (amino acids 107–178). The levels of HBsAg were significantly lower in cells co-transfected with HBV e-, P22/P25, and APOBEC3A, than in cells co-transfected with HBV e-, APOBEC3A, or in cells co-transfected with HBV e-, P22/P25. The levels of HBeAg were lower in cells co-transfected with HBV e-, P22/P25, and APOBEC3A, than in cells co-transfected with HBV e-, P22/P25. Compare with cells transfected with HBV e-, APOBEC3A, or in cells co-transfected with HBV e-, P25/P22, HBV replication intermediates were lower in the cells co-transfected with HBV e-, P25, APOBEC3A, and significantly lower in the cells with HBV e-, P22, APOBEC3A. Conclusions: HBV replication can be inhibited by the interaction of P25/P22 with APOBEC3A protein in the cytoplasm
NLRP3 and MCU are Essential for Ferulic Acid Alleviating Endoplasmic Reticulum- and Mitochondria-Dependent Oxidative Stress and Inflammation in Hyperglycemia-Induced Retinal Pigment Epithelium Cells
No full textBackground: Oxidative stress and inflammation play the central roles in the pathophysiological process of diabetic retinopathy. Our purpose was to elaborate the effect and regulatory mechanism of ferulic acid (FA) in mitigating diabetic retinopathy as well as the functional roles of mitochondrial calcium uniporter (MCU) and NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and their interplay. Methods: Human retinal pigment epithelial cells ARPE-19 were pre-treated with 10 mmol/L FA, or transfected with NLPR3 or MCU siRNA or overexpression plasmids. Afterwards, ARPE-19 cells were exposed to 30 mmol/L high glucose for simulating diabetic retinopathy. Intracellular reactive oxygen species (ROS) generation, cytosolic Ca2+ level, endoplasmic reticulum (ER) and mitochondrial stress, mitochondrial membrane potential were assayed with 2,7-dichlorofluorescein diacetate (DCFH-DA), Fluo-4 acetoxymethyl ester (Fluo-4 AM), ER-Tracker Red, Seahorse XFe96 Analyzer and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining, respectively. MCU, NLRP3, Interleukin-1beta (IL-1β), toll-like receptor 4 (TLR4), nuclear factor κB (NFκB), AKT serine/threonine kinase1 (AKT1) and phosphorylated-Akt1 (p-AKT1) were measured with western blots or immunohistochemistry. Results: Both FA pre-treatment and blockage of NLRP3 mitigated apoptosis, intracellular ROS, cytosolic Ca2+ level as well as ER and mitochondria stress in hyperglycemia-induced ARPE-19 cells. Additionally, MCU-mediated mitochondrial oxidative stress and NLRP3 inflammasome- and TLR4-dependent AKT/NFκB oxidative and inflammatory signaling were alleviated. Blockage of MCU alleviated hyperglycemia-induced NLRP3 inflammasome activation. Conversely, up-regulation of MCU exacerbated hyperglycemia-induced NLRP3 inflammasome- and TLR4-mediated oxidative and inflammatory signaling, which can be attenuated by FA. Similarly, MCU-mediated mitochondrial oxidative stress was mitigated by FA through NLRP3 inhibition. Conclusion: Collectively, we present evidence that NLRP3 and MCU are essential for FA alleviating ER- and mitochondria-dependent oxidative stress and inflammation in hyperglycemia-induced ARPE-19 cells. Disturbance of NLRP3 and MCU transcription regulation opens novel avenues to mitigate diabetic retinopathy