Implications and progression of peroxiredoxin 2 (PRDX2) in various human diseases.

Peroxiredoxin 2 (PRDX2), a characteristic 2-Cys enzyme is one of the foremost effective scavenger proteins against reactive oxygen species (ROS) and hydrogen peroxide (H2O2) defending cells against oxidative stress. Dysregulation of this antioxidant raises the quantity of ROS and oxidative stress implicated in several diseases. PRDX2 lowers the generation of ROS that takes part in controlling several signalling pathways occurring in neurons, protecting them from stress caused by oxidation and an inflammatory harm. Depending on the aetiological variables, the kind of cancer, and the stage of tumour development, PRDX2 may behave either as an onco-suppressor or a promoter. However, overexpression of PRDX2 may be linked to the development of numerous cancers, including those of the colon, cervix, breast, and prostate. PRDX2 also plays a beneficial effect in inflammatory diseases. PRDX2 being a thiol-specific peroxidase, is known to control proinflammatory reactions. The spilling of PRDX2, on the other hand, accelerates cognitive impairment following a stroke by triggering an inflammatory reflex. PRDX2 expression patterns in vascular cells tend to be crucial to its involvement in cardiovascular diseases. In vascular smooth muscle cells, if the protein tyrosine phosphatase is restricted, PRDX2 could avoid the neointimal thickening which relies on platelet derived growth factor (PDGF), a vital component of vascular remodelling. A proper PRDX2 balance is therefore crucial. The imbalance causes a number of illnesses, including cancers, inflammatory diseases, cardiovascular ailments, and neurological and neurodegenerative problems which are discussed in this review.

Implications of Toll-like receptors (TLRs) and their signaling mechanisms in human cancers.

Most essential pattern-recognition receptors regulating innate immune functions are toll-like receptors (TLRs). TLRs are characterized by lack of concurrent epithelial markers and are typically identified by their gene expressions. One major mechanism by which TLRs generate their effector functions is by triggering inflammatory responses. Activation of TLRs can impact initiation, advancement, and control of cancers by regulating the inflammatory microenvironment. Several TLRs have been implicated in human cancers and some of them are identified as cancer biomarkers as well; for example, TLRs 2, 3, 5 are expressed more frequently in most cancers. Knowing the upregulation and downregulation of the TLR genes in human cancers will be useful for the development of newer therapeutic targets which can disrupt the pathways associated with such deregulation. We present here the various TLRs and their functions in human lung, gastric, breast, prostate, oral, ovarian, colorectal, cervical, esophageal, bladder and hepatic cancers.

Role of homeobox d10 gene targeted signaling pathways in cancers.

Homeobox D10 (HOXD10) is a transcription factor from the homeobox gene family that controls cell differentiation and morphogenesis throughout development.Due to their functional interaction, changes in HOXD10 gene expression might induce tumors. This narrative review focuses on how and why the dysregulation in the signaling pathways linked with HOXD10 contributes to the metastatic development of cancer. Organ development and tissue homeostasis need highly conserved homeotic transcription factors from homeobox (HOX) genes. Their dysregulation disrupts regulatory molecule action, causing tumors. The HOXD10 gene is upregulated in breast, gastric, hepatocellular, colorectal, bladder, cholangiocellular carcinoma and prostate cancer. Tumor signaling pathways are affected by HOXD10 gene expression changes. This study examines HOXD10-associated signaling pathway dysregulation, which may alter metastatic cancer signaling. In addition, the theoretical foundations that alter HOXD10-mediated therapeutic resistance in malignancies has been presented. New cancer therapy methods will be simpler to develop with the newly discovered knowledge. This review showed that HOXD10 may be a tumor suppressor gene and a new cancer treatment target signaling pathway.

Recent and advanced therapy for oral cancer.

Oral cancer is a common and deadly kind of tissue invasion, has a high death rate, and may induce metastasis that mostly affects adults over the age of 40. Most in vitro traditional methods for studying cancer have included the use of monolayer cell cultures and several animal models. There is a worldwide effort underway to reduce the excessive use of laboratory animals since, although being physiologically adequate, animal models rarely succeed in exactly mimicking human models. 3D culture models have gained great attention in the area of biomedicine because of their capacity to replicate parent tissue. There are many benefits to using a drug delivery approach based on nanoparticles in cancer treatment. Because of this, in vitro test methodologies are crucial for evaluating the efficacy of prospective novel nanoparticle drug delivery systems. This review discusses current advances in the utility of 3D cell culture models including multicellular spheroids, patient-derived explant cultures, organoids, xenografts, 3D bioprinting, and organoid-on-a-chip models. Aspects of nanoparticle-based drug discovery that have utilized 2D and 3D cultures for a better understanding of genes implicated in oral cancers are also included in this review.

Comparison of Real-time RT-PCR cycle threshold (Ct) values with clinical features and severity of COVID-19 disease among hospitalized patients in the first and second waves of COVID-19 pandemic in Chennai, India.

Introduction: Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) of nasopharyngeal/ oropharyngeal swab has been the gold standard test for detection of SARS-CoV-2 infection The relationship between cycle threshold (Ct) values of rRT-PCR and severity of disease remain disputable and not clearly defined in COVID-19. Methodology: This is a single-centered retrospective observational study conducted at Government Corona Hospital (GCH), Guindy, Chennai. In the present study, we compared the Ct value of rRT-PCR from nasopharyngeal swab specimens with a diverse range of symptoms and disease severity among 240 individuals who were hospitalized with COVID-19, viz., mild cases (MC; n = 160), moderately severe cases (MSC; n = 46) and severe cases (SC; n = 34) in the first and second waves of COVID-19 pandemic. Results: The study included 240 hospitalized COVID-19 patients with a median age of 52 years (range 21 to 90 years). MC, MSC, and SC all had median Ct values of 25.0 (interquartile range - IQR 20.0 to 30.5), 29.5 (IQR 23.0 to 34.0), and 29.0 (IQR 24 to 37.5) for the ORF1ab gene. The Ct value differed significantly between mild vs moderate, and mild vs severe cases. The Ct value of SC group with co-morbidity of type 2 diabetes have a significant difference compared to non-diabetes group (p value <0.05). There was a significant difference in the median Ct value of ORF1ab gene among the MSC group and MC but not in the SC group in the first and second waves of the pandemic (p<0.05). Conclusion: We conclude that SARS-CoV-2 Ct values of rRT-PCR alone does not have a role in aiding severity stratification among patients with COVID-19 since the viral dynamics and Ct value may vary due to the emerging variants that occur in different waves of the pandemic.

Nanosensors for the diagnosis and therapy of neurodegenerative disorders and inflammatory bowel disease.

One of the areas of science which has immensely advanced in the recent years is nanotechnology. This area broadly revolves around matter at scales between 1 and 100 nm, where peculiar phenomena make way for cutting-edge applications. Today, nanotechnology has a daily impact on human life with numerous and varied possible advantages. Nanosensors are one of the products of nanotechnology and any sensor that uses nanoscale phenomena qualifies to be known as a nanosensor. Nanosensors have proven very useful in a number of sectors including medical applications, food quality analysis and agricultural controlling process, etc. One of the major human healthcare applications of nanosensors is for disease diagnosis. With the aid of nanosensors, numerous neurodegenerative disorders and inflammatory diseases are commonly identified and treated of late. Alzheimer's disease (AD) and inflammatory bowel disease fall under the categories of neurodegenerative illnesses and inflammatory diseases. There are more than 20 million cases of (AD) making it the most prevalent neurological condition globally and "inflammatory bowel disease" (IBD) refers to a variety of conditions that cause persistent inflammation of the digestive tract. Here we present a comprehensive account on the utility of nanosensors for the diagnosis and treatment of (AD) and (IBD).

Peptide-based direct electrochemical detection of receptor binding domains of SARS-CoV-2 spike protein in pristine samples.

RNA isolation and amplification-free user-friendly detection of SARS-CoV-2 is the need of hour especially at resource limited settings. Herein, we devised the peptides of human angiotensin converting enzyme-2 (hACE-2) as bioreceptor at electrode interface for selective targeting of receptor binding domains (RBD) of SARS-CoV-2 spike protein (SP). Disposable carbon-screen printed electrode modified with methylene blue (MB) electroadsorbed graphene oxide (GO) has been constructed as cost-efficient and scalable platform for hACE-2 peptide-based SARS-CoV-2 detection. In silico molecular docking of customized 25 mer peptides with RBD of SARS-CoV-2 SP were validated by AutoDock CrankPep. N-terminal region of ACE-2 showed higher binding affinity of - 20.6 kcal/mol with 15 H-bond, 9 of which were < 3 Å. Electrochemical biosensing of different concentrations of SPs were determined by cyclic voltammetry (CV) and chronoamperometry (CA), enabling a limit of detection (LOD) of 0.58 pg/mL and 0.71 pg/mL, respectively. MB-GO devised hACE-2 peptide platform exert an enhanced current sensitivity of 0.0105 mA/pg mL-1 cm-2 (R2 = 0.9792) (CV) and 0.45 nA/pg mL-1 (R2 = 0.9570) (CA) against SP in the range of 1 pg/mL to 1 µg/mL. For clinical feasibility, nasopharyngeal and oropharyngeal swab specimens in viral transport medium were directly tested with the prepared peptide biosensor and validated with RT-PCR, promising for point-of-need analysis.

Transcriptional Profiling and Deriving a Seven-Gene Signature That Discriminates Active and Latent Tuberculosis: An Integrative Bioinformatics Approach.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb.). Our integrative analysis aims to identify the transcriptional profiling and gene expression signature that distinguish individuals with active TB (ATB) disease, and those with latent tuberculosis infection (LTBI). In the present study, we reanalyzed a microarray dataset (GSE37250) from GEO database and explored the data for differential gene expression analysis between those with ATB and LTBI derived from Malawi and South African cohorts. We used BRB array tool to distinguish DEGs (differentially expressed genes) between ATB and LTBI. Pathway enrichment analysis of DEGs was performed using DAVID bioinformatics tool. The protein-protein interaction (PPI) network of most upregulated genes was constructed using STRING analysis. We have identified 375 upregulated genes and 152 downregulated genes differentially expressed between ATB and LTBI samples commonly shared among Malawi and South African cohorts. The constructed PPI network was significantly enriched with 76 nodes connected to 151 edges. The enriched GO term/pathways were mainly related to expression of IFN stimulated genes, interleukin-1 production, and NOD-like receptor signaling pathway. Downregulated genes were significantly enriched in the Wnt signaling, B cell development, and B cell receptor signaling pathways. The short-listed DEGs were validated in a microarray data from an independent cohort (GSE19491). ROC curve analysis was done to assess the diagnostic accuracy of the gene signature in discrimination of active and latent tuberculosis. Thus, we have derived a seven-gene signature, which included five upregulated genes FCGR1B, ANKRD22, CARD17, IFITM3, TNFAIP6 and two downregulated genes FCGBP and KLF12, as a biomarker for discrimination of active and latent tuberculosis. The identified genes have a sensitivity of 80-100% and specificity of 80-95%. Area under the curve (AUC) value of the genes ranged from 0.84 to 1. This seven-gene signature has a high diagnostic accuracy in discrimination of active and latent tuberculosis.

Pooled Testing Strategies for SARS-CoV-2 diagnosis: A comprehensive review.

SARS-CoV-2 has surged across the globe causing the ongoing COVID-19 pandemic. Systematic testing to facilitate index case isolation and contact tracing is needed for efficient containment of viral spread. The major bottleneck in leveraging testing capacity has been the lack of diagnostic resources. Pooled testing is a potential approach that could reduce cost and usage of test kits. This method involves pooling individual samples and testing them 'en bloc'. Only if the pool tests positive, retesting of individual samples is performed. Upon reviewing recent articles on this strategy employed in various SARS-CoV-2 testing scenarios, we found substantial diversity emphasizing the requirement of a common protocol. In this article, we review various theoretically simulated and clinically validated pooled testing models and propose practical guidelines on applying this strategy for large scale screening. If implemented properly, the proposed approach could contribute to proper utilization of testing resources and flattening of infection curve.

Toll-like receptor (TLR) gene expression and immunostimulatory effect of CpG oligonucleotides in hormone receptor positive cell line T47D and triple negative breast cancer cell line MDA-MB-468.

BACKGROUND: We investigated the expression of TLR genes and the effects of CpG ODN in Estrogen Receptor positive, Progesterone Receptor positive breast cancer cell line (T47D) and a triple-negative breast cancer cell line (MDA-MB-468) followed by studying the immunostimulatory activity of CpG oligonucleotides in breast cancer cell lines T47D and MDA-MB-468. MATERIALS AND METHODS: We evaluated the expression pattern of TLR genes (TLR1 to TLR9) in T47D and MDA-MB-468 cells using Real-time qPCR analysis. The intracellular TLR9 protein expression was studied by flow cytometry. The effect of CpG ODN on cell viability was tested using MTT assay. The relative expression of pro-inflammatory (IL6 and TNFα) and anti- inflammatory/immunosuppressive cytokines genes (IL10 and TGF beta1) were examined by Real-time qPCR. RESULTS: We found that MDA-MB-468 cells expressed TLR2, TLR3, TLR6, TLR8, and TLR9 genes and T47D cells expressed TLR3, TRL5, TLR8, and TLR9 genes. Stimulation of TLR9 in vitro with CpG significantly reduced the cell viability of T47D and MDA-MB-468 cells. IL6 cytokine gene expression was significantly reduced in both CpG treated T47D cells and MDA-MB-468 cells. TNFα gene expression was significantly reduced after treatment with CpG in MDA-MB-468 cells but not in T47D cells. IL10 and TGFß1 expression were downregulated in CpG treated T47D cells. Whereas, IL10 and TGFß1 were elevated in CpG treated MDA-MB-468 cells. CONCLUSION: Our in vitro finding gives preliminary evidence that triggering TLR9 using CpG ODN decreases the cell proliferation and alters the pro-inflammatory cytokines in favor of inhibition of hormone receptor positive breast cancer cells T47D and triple negative breast cancer cells MDA-MB-468.

Microarray and pattern miner analysis of AXL and VIM gene networks in MDA­MB­231 cells.

MDA­MB­231 cells represent malignant triple­negative breast cancer, which overexpress epidermal growth factor receptor (EGFR) and two genes (AXL and VIM) associated with poor prognosis. The present study aimed to identify novel therapeutic targets and elucidate the functional networks for the AXL and VIM genes in MDA­MB­231 cells. We identified 71 genes upregulated in MDA­MB­231 vs. MCF7 cells using BRB­Array tool to re­analyse microarray data from six GEO datasets. Gene ontology and STRING analysis showed that 43/71 genes upregulated in MDA­MB­231 compared with MCF7 cells, regulate cell survival and migration. Another 19 novel genes regulate migration, metastases, senescence, autophagy and chemoresistance. The Pattern Miner systems biology tool uses specific genes as inputs or 'baits' to identify outputs from the NCI­60 database. Using five genes regulating cancer cell migration (AXL, VIM, EGFR, CAPN2, and COL4A1) as input 'baits', we used pattern miner to identify statistically significant, co­expressed genes from the list of 71 genes upregulated in MDA­MB­231 compared with MCF7 cells. Outputs were subsets of the 71 genes, which showed significant co­expression with one or more of the five input genes. These outputs were used to develop functional networks for AXL and VIM. Analysis of these networks verified known properties of AXL and VIM, and suggested novel functions for these two genes. Thus, genes in the AXL network promote migration, metastasis and chemoresistance, whereas the VIM gene network regulates novel tumorigenic processes, such as lipogenesis, senescence and autophagy. Notably, these two networks contain 12 genes not reported for TNBC.

Characterization of clonal immunoglobulin heavy (IGH) V-D-J gene rearrangements and the complementarity-determining region in South Indian patients with precursor B-cell acute lymphoblastic leukemia

BACKGROUND: This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements. METHODS: IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool. RESULTS: Clonal IGH rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1-IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes, IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones, respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average, Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively. CONCLUSION: The IGHV3 gene was frequently used whereas lower frequencies of IGHV5 and IGHV6 and a higher frequency of IGHV4 were detected in children compared with young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements in precursor-B-ALL did not show any significant age-associated genotype pattern attributed to our population.

Unusual case of hepatic metastasis in follicular thyroid carcinoma detected using I-131 whole body scintigraphy and single-photon emission computerized tomography/computerized tomography.

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Among these presentations, metastasis to the liver is even more unusual. Only 11 cases of DTC with liver metastasis were previously reported in the literature. We present a 55-year-old male on Iodine-131 whole body scintigraphy showed intense uptake in thyroid bed, metastasis in both lungs and right lobe of the liver. Radioiodine concentration in liver metastases made him amenable to high-dose radioiodine therapy patient.

Paget's disease of pelvis mimicking metastasis in a patient with lung cancer evaluated using staging and follow-up imaging with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography.

Paget's disease of bone is a benign disease, of uncertain etiology, characterized by an accelerated turnover, that is, bone resorption and formation. Paget's disease may be present in up to 5% of the population, and the majority of cases are asymptomatic. We report the imaging findings of Paget's disease of pelvis discovered incidentally in patient with lung cancer evaluated by fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging. FDG PET-CT scan showed intense uptake in the right lung lower lobe primary and mediastinal lymph nodes. Furthermore, increased uptake noted in left hemipelvis suggestive of Paget's disease. He underwent follow-up FDG PET-CT after chemotherapy showed decrease in lung mass and mediastinal nodes. However, the uptake in left hemipelvis remains same confirming Paget's disease.