Exploring Mammalian Heme Peroxidases: A comprehensive review on the structure and function of Myeloperoxidase, Lactoperoxidase, Eosinophil peroxidase, Thyroid peroxidase and Peroxidasin.

The peroxidase family of enzymes is a ubiquitous cluster of enzymes primarily responsible for the oxidation of organic and inorganic substrates. The mammalian heme peroxidase subfamily is characterized by a covalently linked heme prosthetic group which pays a key role in the oxidation of halides and psuedohalides in their respective hypohalous acid and hypothiocyanous acid under the influence of H2O2 as substrate. The members of the heme peroxidase family include Lactoperoxidase (LPO), Eosinophil peroxidase (EPO), Myeloperoxidase (MPO), Thyroid peroxidase (TPO) and Peroxidasin (PXDN). The biological activity of LPO, MPO and EPO pertains to antibacterial, antifungal and antiviral while TPO is involved in the biosynthesis of the thyroid hormone and PXDN helps maintain the ECM. While these enzymes play several immunomodulatory roles, aberrations in their activity have been implicated in diseases such as myocardial infarction, asthma and Alzheimer's amongst others. The sequence and structural similarities amongst the members of the family are strikingly high while the substrate specificities and subcellular locations vary. Hence, it becomes important to provide a consortium of information regarding the members to study their function, pathological and clinical function.

Evaluation of Emerging Predictors for Contrast-Induced Nephropathy in High-Risk Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: The objective of this study is to investigate the occurrence and factors that influence the development of contrast-induced nephropathy (CIN) in high-risk patients undergoing angioplasty and to evaluate the effectiveness of the Mehran risk score in predicting CIN among this patient population. MATERIALS AND METHOD: This prospective, observational study enrolled patients undergoing elective coronary angiography or a percutaneous coronary intervention (PCI) procedure. The patients were stratified into four risk groups based on the Mehran risk score, a validated tool for predicting the risk of CIN. Univariate and multivariate analyses were conducted to evaluate the risk factors associated with the development of CIN. A p-value of <0.05 was considered to indicate statistical significance. RESULTS: During the study period, a total of 55 high-risk patients underwent PCI. The incidence of CIN was 25.5% (n=14). Univariate and multivariate analyses revealed that age >75 years and estimated glomerular filtration rate (eGFR) <60 (p<0.05) were independently associated with a significantly increased risk of developing CIN. A considerable proportion of patients (23; 41.8%) in the study were categorized as having an intermediate risk for CIN based on the Mehran risk score. CONCLUSION: This study observed a high incidence of CIN and encourages the use of predictive tools like the Mehran risk score to assess the risk of CIN occurrence, with age over 70 years and eGFR less than 60 emerging as significant.

Assessing the Role of Transvaginal Sonography in Post-menopausal Bleeding: A Less Invasive Approach to Identify Endometrial Carcinoma.

Background Post-menopausal bleeding (PMB) is a very common complaint seen in current practice. Endometrial carcinoma (EC) commonly presents with PMB. Endometrial biopsy is the tool for definitive diagnosis, but it is invasive. Transvaginal sonography (TVS) is a non-invasive tool that can help us in the initial evaluation of such patients. Methods A prospective observational study was conducted on 76 women with PMB. TVS and histopathological study, along with basic evaluation and investigations, were performed on all participants, followed by necessary treatment and follow-up. Data collected were studied and statistically analyzed. Results A maximum of 27.63% (n=21) of patients had endometrial atrophy causing their PMB. Proliferative endometrium was observed in 21.06% (n=16) of cases, 13.15% (n=10) of women had secretory endometrium, 23.68% (n=18) had simple endometrial hyperplasia, 3.94% (n=3) had complex endometrial hyperplasia without atypia, and another 3.94% (n=3) had complex endometrial hyperplasia with atypia. Further classifying, women with benign hyperplasia included 27.63% (n=21) and those with atypical hyperplasia included 3.94% (n=3). Out of the 5.26% (n=4) patients diagnosed with EC on histopathology, TVS identified carcinoma in 75% (n=3) cases. This indicates that the sensitivity and specificity of TVS in detecting EC are 75% and 100%, respectively. The positive predictive value (PPV) is 100%, the negative predictive value (NPV) is 98.63%, and the accuracy is 98.68%. Conclusion If the cut-off for endometrial thickness is set at 4 mm, then TVS proves to be an effective and reliable tool for screening and diagnosing EC. It can thus serve as a safe threshold to screen patients with PMB using TVS.

Role of the Surgical Approach in the Treatment of Eagle Syndrome.

Introduction Eagle syndrome is a rare and an often misdiagnosed entity in otorhinolaryngology. Objective To determine the efficacy of the surgical treatment for Eagle syndrome. Methods The present prospective study included 25 patients who presented with complaints of pain in the throat, ear, and neck, as well as difficulty and/or pain while swallowing; they were assessed for Eagle syndrome. As per patient profile, we performed a clinical assessments along with orthopantomograms (OPGs), three-dimensional computed tomography (3D CT) scans, and cone beam computed tomography (CBCT). Pain was assessed pre- and postoperatively through the Numerical Rating Scale-11 (NRS-11), whose score ranges from 0 to 10. Microscopic tonsillo-styloidectomy was performed in cases in which the conservative treatment failed to relieve pain. Results The mean age of the entire study population was of 36.08 ± 7.19 years, and the male-to-female ratio was of 1.08:1. Referred otalgia was the commonest (44%) complaint. Radiologically, out of 25 patients, 20 patients presented elongated styloid processes. The longest symptomatic styloid process measured radiographically was of 64.7 mm while the shortest was of 28.2 mm. Out of 20 patients, 12 underwent surgery. The postoperative pain assessment through the NRS-11 was performed on day 0 (3.83 ± 0.83), day 7 (1.5 ± 0.52), week 4 (0.5 ± 0.52), and week 12 (0.41 ± 0.51). By 12 weeks, 7 patients were symptom-free, while 5 patients still reported mild pain. Conclusion Eagle syndrome associated with an elongated styloid process is not a rarity, but it often goes undiagnosed. Microscopic tonsillo-styloidectomy shows excellent results in the management of patients with Eagle syndrome.

C-reactive protein and procalcitonin: As predictor biomarkers of severity and outcome in children with community-acquired pneumonia.

Our cohort study aimed to compare serum C-reactive protein (CRP) and procalcitonin (PCT) levels in children with community-acquired pneumonia defined by WHO. The former differentiated between pneumonia and severe pneumonia while the latter was better for the outcome of pneumonia.

Identification and targeting of metastatic biomarkers for hepatocellular carcinoma therapeutics using small molecules library of curcumin analogues.

The understanding of the molecular basis of complex diseases like hepatocellular carcinoma (HCC) needs large datasets of multiple genes and proteins involved in different phenomenon of its development. This study focuses on the molecular basis of HCC and the development of therapeutic strategies. We analyzed a dataset of 5475 genes (Homo sapiens) involved in HCC hallmarks, involving comprehensive data on multiple genes and frequently mutated genes. As HCC is characterized by metastasis, angiogenesis, and oxidative stress, exploration of genes associated with them has been targeted. Through gene ontology, functional characterization, and pathway enrichment analysis, we identified target proteins such as Lysyl oxidase, Survivin, Cofilin, and Cathepsin B. A library of curcumin analogs was used to target these proteins. Tetrahrydrocurcumin showed promising binding affinities for all four proteins, suggesting its potential as an inhibitor against these proteins for HCC therapy.

Comparative evaluation of divergent concoction of NGF, BDNF, EGF, and FGF growth factor's role in enhancing neuronal differentiation of adipose-derived mesenchymal stem cells.

MSCs (Mesenchymal Stem Cells) can differentiate into various lineages, including neurons and glial cells. In the past few decades, MSCs have been well explored in the context of neuronal differentiation and have been reported to have the immense potential to form distinct kinds of neurons. The distinguishing features of MSCs make them among the most desired cell sources for stem cell therapy. This study involved the trans-differentiation of Adipose-derived human Mesenchymal Stem Cells (ADMSCs) into neurons. The protocol employs a cocktail of chemical inducers in different combinations, including Brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), and Nerve growth factor (NGF) Fibroblastic growth factor (FGF), in induction media. Both types have been successfully differentiated into neurons, confirmed by morphological aspects and the presence of neural-specific markers through RT-PCR (Reverse transcription polymerase chain reaction) studies and immunocytochemistry assay. They have shown excellent morphology with long neurites, synaptic connections, and essential neural markers to validate their identity. The results may significantly contribute to cell replacement therapy for neurological disorders.

Inhibition of LINGO1 as a therapeutic target to promote axonal regeneration and repair for neurological disorders.

The Central nervous system is blemished by the high incidence of neurodegenerative diseases, which is known to cause disfiguration of regeneration and repair of axonal growth. Recognition of proteins that act as agents of repressing such repair has become the norm to tackle these abominable conditions. One such protein is LINGO1 that act as a repressor for axonal growth. Being one of the critical causative agents of several neurodegenerative pathways. Consequently, its inhibition may tend to help the outcomes of regenerative technologies aiming to outweigh the symptoms of neurodegenerative diseases. For this objective, LINGO1 was targeted with pharmacophore analogs of Fasudil and Ibuprofen, as they are known to have a deterring effect against the concerned protein. 1-Tosyl-2-(chloromethyl)-2,3-dihydro-1H-indole was found showing the least binding score of - 6.8, with verified ADMET admissibility. The pharmacological activity of the said ligand was estimated with QSAR tool showing favourable electro-steric model. All this was finally collaborated with a molecular dynamics simulation study which exhibited a stable structure compatibility of the ligand with LINGO-1. Further, the efficacy of the compound can be evaluated through experimental studies for inferring its future potential and utilization as an effective means to tackle neuronal regeneration and remyleination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03789-4.

Latent Tuberculosis Screening Cascade for Non-US-Born Persons in a Large Health System.

Review of electronic health records revealed substantial drop-off at each stage of the latent tuberculosis infection (LTBI) care cascade among non-US-born persons in an academic primary care system. Of 5148 persons eligible for LTBI screening, 1012 (20%) had an LTBI test, and 140 (48%) of 296 LTBI-positive persons received LTBI treatment.

Therapeutical growth in oligodendroglial fate induction via transdifferentiation of stem cells for neuroregenerative therapy.

The merits of stem cell therapy and research are undisputed due to their widespread usage in the treatment of neurodegenerative diseases and demyelinating disorders. Cell replacement therapy especially revolves around stem cells and their induction into different cell lineages both adult and progenitor - belonging to each germ layer, prior to transplantation or disease modeling studies. The nervous system is abundant in glial cells and among these are oligodendrocytes capable of myelinating new-born neurons and remyelination of axons with lost or damaged myelin sheath. But demyelinating diseases generate tremendous deficit between myelin loss and recovery. To compensate for this loss, analyze the defects in remyelination mechanisms as well as to trigger full recovery in such patients mesenchymal stem cells (MSCs) have been induced to transdifferentiate into oligodendrocytes. But such experiments are riddled with problems like prolonged, tenuous and complicated protocols that stretch longer than the time taken for the spread of demyelination-associated after-effects. This review delves into such protocols and the combinations of different molecules and factors that have been recruited to derive bona fide oligodendrocytes from in vitro differentiation of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and MSCs with special focus on MSC-derived oligodendrocytes.

Jackfruit seed flour-based waffle ice cream cone: Optimization of ingredient levels using response surface methodology.

The jackfruit seed has excellent nutritional food value which can help to produce healthy and nutritious food products. In this study, wheat flour was partially replaced by jackfruit seed flour (JSF) for the formulation of waffle ice cream cones. The amount of wheat flour added in the batter on the basis of amount of added JSF. The JSF was added after optimization using response surface methodology in a batter formulation for waffle ice cream cones. The waffle ice cream cone was made from 100% wheat flour, was considered as control, and used to compare JSF supplemented waffle ice cream cones. Substitution of wheat flour with JSF has affected the nutritional and sensorial attributes of waffle ice cream cone. In regard to its protein content, ice cream permeability hardness, crispness, and overall acceptability. The protein content was increased (14.55%) after the addition of jackfruit seed flour up to 80% from control. The cone was supplemented with 60% of JSF resulted to the higher values of crispiness and overall acceptability as compared to other waffle ice cream cones. As the JSF have high value in water/oil absorption capacities, therefore it could be utilized into other value-added food products as whole or partial replacement of wheat flour.

Modulation of GPCR receptors common to gut inflammatory diseases and neuronal disorders, Alzheimer's and Parkinson's diseases as druggable targets through Withania somnifera bioactives: an in silico study.

Microorganisms in human gastrointestinal tract have profound influence on the transformation of food into metabolites which can impact human health. Along with playing crucial roles in regulating and modulating various metabolic reactions and life processes, dysbiosis of gut microbiota also affects the permeability of gut and blood-brain barrier. This increases the chance of age-related neurological disorders' like Alzheimer's and Parkinson's diseases. Withania somnifera (W. somnifera) has been proclaimed as a virtuous plant for the treatment of neurodegenerative diseases and many other problems. We have studied the bioactive components of W. somnifera for combined treatment of gut-dysbiosis led bowel diseases (Inflammatory Bowel Disease, Irritable Bowel Syndrome) and the most common neurodegenerative diseases through common potential targets. This approach can solve along with curing the neurodegenerative diseases, the factors causing these diseases would also be obstructed from entering the brain, consonantly curing Inflammatory Bowel Disease and Irritable Bowel Syndrome. Our work on GPCR receptors common to gut inflammatory diseases and neuronal disorders through Network Pharmacology, Molecular docking and Dynamic Simulation approach has shown that modulation of these receptors with bioactive compounds present in W. somnifera can result in effective control of these diseases. We have found five proteins (HTR1A, HTR1B, HTR2A, HTR2B & HTR7) and five best lead compounds (Withanolide A, B, E, Q & Anahygrine) against these targets after molecular docking analysis. Our simulation studies have finally shown that amongst these five HTR1A and HTR7 proteins are the best targets with the leads Withanolide E and Withanolide A against them, respectively.Communicated by Ramaswamy H. Sarma.

The cross-talk between mucormycosis, steroids and diabetes mellitus amidst the global contagion of COVID-19.

Mucormycosis is an opportunistic fungal disease that targets individuals having an impaired immune system due to a wide array of risk factors including HIV-AIDS, immunosuppressive therapy, diabetes mellitus, etc. The current explosive outbreak of coronavirus disease 2019 (COVID-19) has become the latest threat to such patients who are already susceptible to secondary infections. Physiological outcomes of COVID-19 end up in a cascade of grave alterations to the immunological profile and irreparable harm to their respiratory passage, heart and kidneys. Corticosteroidal treatment facilitates faster recovery and alleviates the adverse pathological effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But clinical reports lend this approach a darker perspective especially if these patients have pre-existing diabetes mellitus. The mucormycotic fungal genera belonging to the order Mucorales not only survive but thrive under the comorbidity of COVID-19 and diabetes, often staying undetected until they have inflicted irreversible damage. Steroidal usage has been noted to be a common thread in the sudden spurt in secondary fungal infections among COVID-19 cases. Once considered a rare occurrence, mucormycosis has now acquired a notoriously lethal status in mainstream medical hierarchy. We set out to investigate whether corticosteroidal therapy against COVID-19 emboldens the development of mucormycosis. We also assess the conditions brought forth by steroidal usage and uncontrolled progression of diabetes in COVID-19 cases and their effect on the susceptibility towards mucormycosis.

Optional MRI sequences for LI-RADS: why, what, and how?

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver worldwide. Noninvasive diagnosis of HCC is possible based on imaging features, without the need for tissue diagnosis. Liver Imaging Reporting and Data System (LI-RADS) CT/MRI diagnostic algorithm allows for standardized radiological interpretation and reporting of imaging studies for patients at high risk for HCC. Diagnostic categories of LR-1 to LR-5 designate each liver observation to reflect the probability of overall malignancy, HCC, or benignity based on imaging features, where LR-5 category has > 95% probability of HCC. Optimal imaging protocol and scanning technique as described by the technical recommendations for LI-RADS are essential for the depiction of features to accurately characterize liver observations. The LI-RADS MRI technical guidelines recommend the minimum required sequences of T1-weighted out-of-phase and in-phase Imaging, T2-weighted Imaging, and multiphase T1-weighted Imaging. Additional sequences, including diffusion-weighted imaging, subtraction imaging, and the hepatobiliary phase when using gadobenate dimeglumine as contrast, improve diagnostic confidence, but are not required by the guidelines. These optional sequences can help differentiate true lesions from pseudolesions, detect additional observations, identify parenchymal observations when other sequences are suboptimal, and improve observations conspicuity. This manuscript reviews the optional sequences, the advantages they offer, and discusses technical optimization of these sequences to obtain the highest image quality and to avoid common artifacts.

Pseudomonas-specific 16S rRNA insect gut-microbiome profiling using next-generation sequencing.

We present a detailed protocol for Pseudomonas-specific 16S rRNA gut-microbiome profiling of brown planthopper (BPH) populations collected across changing climates and geographical locations using next-generation sequencing. We provide a technique for comparative analysis of Pseudomonas species structure and composition across BPH populations. Additionally, using qPCR we quantify the titers of Pseudomonas species in BPH. This protocol can be adopted for analyzing microbiome dynamics and monitoring populations of other pests, a crucial aspect for understanding their biodiversity, speciation, and adaptations. For complete details on the use and execution of this protocol, please refer to Gupta et al. (2022).1.

Epigenetic Diversity Underlying Seasonal and Annual Variations in Brown Planthopper (BPH) Populations as Revealed by Methylation- sensitive Restriction Assay.

Background: The brown planthopper (BPH) is a monophagous sap-sucking insect pest of rice that is responsible for massive yield loss. BPH populations, even when genetically homogenous, can display a vast range of phenotypes, and the development of effective pest-management strategies requires a good understanding of what generates this phenotypic variation. One potential source could be epigenetic differences. Methods: With this premise, we explored epigenetic diversity, structure and differentiation in field populations of BPH collected across the rice-growing seasons over a period of two consecutive years. Using a modified methylation-sensitive restriction assay (MSRA) and CpG island amplification-representational difference analysis, site-specific cytosine methylation of five stress-responsive genes (CYP6AY1, CYP6ER1, Carboxylesterase, Endoglucanase, Tf2-transposon) was estimated, for identifying methylation-based epiallelic markers and epigenetic variation across BPH populations. Results: Using a cost-effective and rapid protocol, our study, for the first time, revealed the epigenetic component of phenotypic variations in the wild populations of BPH. Besides, results showed that morphologically indistinguishable populations of BPH can be epigenetically distinct. Conclusion: Screening field-collected BPH populations revealed the presence of previously unreported epigenetic polymorphisms and provided a platform for future studies aimed at investigating their significance for BPH. Furthermore, these findings can form the basis for understanding the contribution(s) of DNA methylation in providing phenotypic plasticity to BPH.

Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals.

Introduction: Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome. Methods: By combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals. Results: Based on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1ß, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors. Discussion: In conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.

Changing Trends in COVID-19 Symptomatology: A Survey-Based Analysis.

India currently ranks the highest in the world with over 3.86 lakhs new COVID-19 cases per day. With a spike in the number of cases in the second wave of COVID-19 in 2021 compared to the first wave of the outbreak in 2020, there have been varied clinical manifestations among masses. This study aimed to determine the changing trends in prevalence of COVID-19 symptoms during the pandemic. A cross-sectional study among 166 individuals was carried out using a self-designed survey-based questionnaire. Two groups were made on the basis of symptoms and compared: Group A- patients who tested COVID-19 positive in 2020 and Group B- patients who tested COVID-19 positive in 2021. 130 participants (78.31%) had tested positive for COVID-19, out of which 110 (84.62%) were symptomatic and 20 (15.38%) were asymptomatic. Fever was the most common presenting symptom (27.69%) followed by difficulty in breathing (24.62%). Group A individuals (n = 37), reported fever as the most common presenting symptom (45.95%), followed by body ache (13.51%); while those in Group B (n = 93) reported difficulty in breathing (33.33%) followed by fever (20.43%). The most common general symptoms were fever and difficulty in breathing while sore throat, cough and anosmia were the most common ENT symptoms. 57.83% had been vaccinated out of which 38.55% experienced symptoms post-vaccination. The prevalence of symptoms in the first and second wave of the pandemic can help in better understanding of the changing symptomatology of SARS-CoV-2 virus.

COVID-19 Associated Mucormycosis with Newly Diagnosed Diabetes Mellitus in Young Males - A Tertiary Care Experience

Abstract Introduction Patients with a history of or active COVID-19 infection are predisposed to the development of opportunist bacterial and fungal infections. A rising incidence of a rare occurring fungal infection earlier, called mucormycosis, has been reported in abundance across the globe since March 2021, especially in India just as the second wave of COVID-19 began, caused by the trifecta of hyperglycemia (new-onset or exacerbation of pre-existing diabetes), oxygen therapy (invasive or noninvasive ventilation), and prolonged intake of steroids. Objective The present study aimed at assessing the prevalence of post-COVID mucormycosis in males of younger age group and spread of rhino-orbital-cerebral mucormycosis (ROCM). Methods A case-control study was performed over a period of 3 months among 60 male patients with confirmed diagnosis of mucormycosis. Individuals < 40 years old were included in the case group (n = 30), while those > 40 years old were included as controls (n = 30). Disease spread was assessed in three types of ROCM, that is, rhinomaxillary, rhino-orbital, and rhino-orbito-cerebral mucormycosis. Results In the control group, the mean age was 48.47 years old, the mean HbA1c was 10.62 ± 1.88%, with most of them suffering from rhino-orbital mucormycosis. In the case group, the mean age was 31.57 years old, with a mean HbA1c of 10.11 ± 2.46%, and most patients had rhinomaxillary mucormycosis. The duration of steroid intake and mode of oxygen therapy were found to be significant in the severity of ROCM. Conclusion Rising cases of post-COVID mucormycosis have brought to light the fatal consequences of prolonged use of steroids and oxygen therapy towards the development and spread of ROCM among young and middle-aged males.