Role of epigenetics in carcinogenesis: Recent advancements in anticancer therapy.

The role of epigenetics in the etiology of cancer progression is being emphasized for the past two decades to check the impact of chromatin modifiers and remodelers. Histone modifications, DNA methylation, chromatin remodeling, nucleosome positioning, regulation by non-coding RNAs and precisely microRNAs are influential epigenetic marks in the field of progressive cancer sub-types. Furthermore, constant epigenetic changes due to hyper or hypomethylation could efficiently serve as effective biomarkers of cancer diagnosis and therapeutic development. Ongoing research in the field of epigenetics has resulted in the resolutory role of various epigenetic markers and their inhibition using specific inhibitors to arrest their key cellular functions in in-vitro and pre-clinical studies. Although, the mechanism of epigenetics in cancer largely remains unexplored. Nevertheless, various advancements in the field of epigenetics have been made through transcriptome analysis and in-vitro genome targeting technologies to unravel the applicability of epigenetic markers for future cancer therapeutics and management. Therefore, this review emphasizes on recent advances in epigenetic landscapes that could be targeted/explored using novel approaches as personalized treatment modalities for cancer containment.

Lichens as a repository of bioactive compounds: an open window for green therapy against diverse cancers.

Lichens, algae and fungi-based symbiotic associations, are sources of many important secondary metabolites, such as antibiotics, anti-inflammatory, antioxidants, and anticancer agents. Wide range of experiments based on in vivo and in vitro studies revealed that lichens are a rich treasure of anti-cancer compounds. Lichen extracts and isolated lichen compounds can interact with all biological entities currently identified to be responsible for tumor development. The critical ways to control the cancer development include induction of cell cycle arrests, blocking communication of growth factors, activation of anti-tumor immunity, inhibition of tumor-friendly inflammation, inhibition of tumor metastasis, and suppressing chromosome dysfunction. Also, lichen-based compounds induce the killing of cells by the process of apoptosis, autophagy, and necrosis, that inturn positively modulates metabolic networks of cells against uncontrolled cell division. Many lichen-based compounds have proven to possess potential anti-cancer activity against a wide range of cancer cells, either alone or in conjunction with other anti-cancer compounds. This review primarily emphasizes on an updated account of the repository of secondary metabolites reported in lichens. Besides, we discuss the anti-cancer potential and possible mechanism of the most frequently reported secondary metabolites derived from lichens.

Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.

The Role of Environmental Toxicant-Induced Oxidative Stress in Male Infertility.

Infertility is a serious public health issue affecting around 15% of couples globally. Of the 60-80 million people of reproductive age affected by infertility, 40-50% are due to male factor while 30-40% of cases are still idiopathic. The recent global deterioration in sperm quality raises apprehensions regarding the toxic effects of environmental pollutants on reproductive health of males. Environmental toxicants have shown strong evidences for inducing oxidative stress affecting spermatogenesis severely, thereby leading to reduced sperm motility, count, and DNA damage. Reactive oxygen species (ROS) influences the spermatozoa development and transit process both internally and externally. Low level of ROS is indispensable for critical physiological sperm processes like sperm capacitation, motility, acrosome reaction, hyper-activation, sperm-oocyte interaction, etc., while excessive ROS disrupt antioxidant molecules which is detrimental to normal functioning of the sperm. Hence, identification of potential environmental toxicant may have clinical relevance for early screening and diagnosis of male infertility.

Emerging biomarkers and clinical significance of HPV genotyping in prevention and management of cervical cancer.

Cervical cancer is a growing and serious problem world-wide in women, but more acute in developing countries especially in Indian subcontinent. The main causative agent for the disease is Human Papilloma Virus (HPV). The history of the cervical cancer goes back to eighteenth century as the HPV infection is reported since 1800s. Presently, the genetic structure of HPV is well defined. Several screening tests including cytology and visual based screening and high risk HPV testing are available. Also available are various clinical and commercial diagnostic tests. However due to the lack of awareness and population-based screening programs, the morbidity and mortality rate is alarmingly high. There are new emerging biomarkers including E6/E7 mRNA, p16ink4a, markers of aberrant S-phase induction, chromosomal abnormalities and miRNAs along with advanced genotyping methods. These markers have clinical significance and are helpful in disease prevention and management. Further, recent advancement in the field of metagenomics has increased the prospects of identifying newer microbes, viruses hitherto reported thus far in the context of HPV infection. Analysis of HPV cases using modern tools including genotyping using more powerful biomarkers is envisaged to enhance the prospects of early diagnosis, better prognosis, more reliable treatment and eventual management of the disease.

The interplay among Th17 and T regulatory cells in the immune dysregulation of chronic dermatophytic infection.

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17  cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research.

TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis.

BACKGROUND: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. RESULTS: The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-ß levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. CONCLUSIONS: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

AA genotype of cyclin D1 G870A polymorphism increases breast cancer risk: Findings of a case-control study and meta-analysis.

BACKGROUND: Cyclin D1 (CCND1) polymorphisms, a regulator of the cell cycle progress from G1 to the S phase, may lead to uncontrolled cell proliferation and lack of apoptosis. G870A, a common single-nucleotide polymorphism in CCND1 influences breast cancer risk. However, the association between G870A polymorphism and breast cancer risk is ambiguous so far. MATERIALS AND METHODS: In this case-control study, we analyzed the role of G870A polymorphism with breast cancer risk in Indian women. A meta-analysis of 18 studies was also performed to elucidate this association by increasing statistical power. RESULTS: In our case-control study, significant risk association of the CCND1 G870A AA genotype with breast cancer in total cohort (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64-5.42; P value, 4.96e-04) and premenopausal women (OR, 3.31; 95% CI, 1.54-7.08; P value, .003) was found. The results of the meta-analysis showed that AA genotype of the CCND1 G870A polymorphism significantly increases breast cancer risk in total pooled data (AA vs GG+GA: OR = 1.20; 95% CI = 1.03 to 1.39; P value, 0.016*) and Caucasian (AA vs GG+GA: OR = 1.22; 95% CI = 0.99 to 1.51; P value, .056*) but not in Asian population. Further, a significant protective association with breast cancer was also found in the GA vs AA comparison model in pooled data (OR = 0.73; 95% CI = 0.58 to 0.92; P value, .007*) as well as in Caucasian subgroup (OR = 0.62; 95% CI = 0.49 to 0.94; P value, .022*). CONCLUSION: CCND1 G870A AA genotype was found associated with breast cancer risk. Future association studies considering the environmental impact on gene expression are required to validate/explore this association.

Bioengineered intravaginal isolate of Lactobacillus plantarum expresses algal lectin scytovirin demonstrating anti-HIV-1 activity.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.

Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases.

BACKGROUND: Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. METHODS: We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. RESULTS: We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. CONCLUSION: Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Typical & atypical enteropathogenic Escherichia coli in diarrhoea & their role as carrier in children under five.

BACKGROUND & OBJECTIVES: Multidrug-resistant enteropathogenic Escherichia coli (EPEC) is responsible for a large number of cases of infantile diarrhoea in developing countries, causing failure in treatment with consequent health burden and resulting in a large number of deaths every year. This study was undertaken to determine the proportion of typical and atypical EPEC in under five children with diarrhoea and controls, their function as a carriage and to identify virulent genes associated with them. METHODS: During the study period, 120 stool samples including 80 from controls children were collected and analyzed for the presence of EPEC using standard bacteriological methods. Isolates were subjected to antimicrobial testing by disc diffusion method. Isolates confirmed as E. coli by phenotypic method were further tested for the presence of attaching and effacing (eae) and bundle-forming pilus (bfpA) genes by real-time SYBR Green-based polymerase chain reaction. RESULTS: All isolates were tested for the presence of EPEC. The frequency of typical EPEC was 20 and 16.25 per cent whereas the frequency of atypical EPEC strains was 5 and 23.75 per cent in patients and controls, respectively (PbfpA was seen in 45 and 18.75 per cent isolates of diarrhoeal patients and controls, respectively. INTERPRETATION & CONCLUSIONS: Our results showed that typical EPEC was a common cause of diarrhoea, but at the same time, atypical EPEC was emerging as colonizers in the intestine of children with and without diarrhoea in and around Delhi. Children can be considered asymptomatic carriers of these pathogens and can transmit them to other susceptible children. Adequate steps need to be taken to stop these strains from developing and spreading further.

Meta-analysis Reveals No Association of DNMT3B -149 C>T Gene Polymorphism With Overall Cancer Risk.

BACKGROUND: DNA methyltransferase-3B (DNMT3B) plays a key role in establishment and maintenance of genomic methylation patterns. Polymorphism in promoter region -149 C>T (C46359T) of DNMT3B gene may alter DNMT3B activity which leads to increased susceptibility to cancer. Inconsistent results regarding this have been reported in a number of studies. OBJECTIVE: To carry out a meta-analysis of the studies reported to assess the precise relationship between the DNMT3B -149 C>T polymorphism and the overall cancer risk. METHOD: PubMed (MEDLINE) web database was searched for the studies concerning DNMT3B -149 C>T polymorphism and its association with cancer risk. The pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated for all the genetic models, from the selected case-control studies, by meta-analysis. RESULTS: Overall eighteen studies containing 5583 cancer cases and 7618 controls were analyzed. No significant risk was observed overall for T allele carrier (T vs. C: p=0.303; OR=1.032, 95% CI=0.972-1.097), homozygous (TT vs. CC: p=0.336; OR=1.063, 95% CI=0.939-1.204), heterozygous (CT vs. CC: p=0.802; OR=1.022, 95% CI=0.860-1.216), dominant (TT vs. CC+CT: p=0.298; OR=1.101, 95% CI=0.919-1.319) and recessive (TT+CT vs. CC: p=0.656; OR=1.021, 95% CI=0.931-1.121) genetic models. Subgroup analysis of Asian and Caucasian populations also did not demonstrate any cancer risk in all the genetic models studied. CONCLUSION: Our meta-analysis proposes that the DNMT3B -149 C>T polymorphism may not be an independent predisposing factor for the risk of cancer. However, larger sample size and expression studies are required to confirm the observation.

Possible Role of Trichophytin Antigen in Inducing Impaired Immunological Clearance of Fungus in Onychomycosis.

The immunology of onychomycosis is poorly understood. Th1 and Th17 are the principal effector cells responsible for protective immunity against fungi, while it is assumed that Th2 responses are associated with deleterious effects. The study was conducted to appraise the role of interleukin-6 (IL-6), transforming growth factor ß (TGF-ß) and immunoglobulin E (IgE) in onychomycosis patients and to study skin reactivity to trichophytin antigen in them. Serum samples of 60 cases of chronic onychomycosis and 30 healthy controls were assayed for serum IgE, IL-6 and TGF-ß levels using specific immunoassay kits; 0.01 ml of trichophytin antigen, Candida antigen and phosphate-buffered saline using separate syringes were injected intradermal at three independent sites of the forearm in cases and controls. Serum IL-6 levels were significantly lower in cases as compared to controls, while serum TGF-ß levels in both cases and controls were comparable. Serum IgE levels in cases were significantly higher when compared with controls. Thirty-eight patients showed immediate hypersensitivity response to trichophytin antigen, while none showed delayed hypersensitivity reaction to trichophytin antigen. Constant fungal antigenic stimuli induce a state of anergy as indicated by low serum IL-6 levels and the absence of delayed hypersensitivity reaction to trichophytin antigen in cases, leading to chronicity of infection. High total IgE may indicate a high probability of prior fungal sensitization.

The Impact of Artificial Intelligence on Microbial Diagnosis.

Traditional microbial diagnostic methods face many obstacles such as sample handling, culture difficulties, misidentification, and delays in determining susceptibility. The advent of artificial intelligence (AI) has markedly transformed microbial diagnostics with rapid and precise analyses. Nonetheless, ethical considerations accompany AI adoption, necessitating measures to uphold patient privacy, mitigate biases, and ensure data integrity. This review examines conventional diagnostic hurdles, stressing the significance of standardized procedures in sample processing. It underscores AI's significant impact, particularly through machine learning (ML), in microbial diagnostics. Recent progressions in AI, particularly ML methodologies, are explored, showcasing their influence on microbial categorization, comprehension of microorganism interactions, and augmentation of microscopy capabilities. This review furnishes a comprehensive evaluation of AI's utility in microbial diagnostics, addressing both advantages and challenges. A few case studies including SARS-CoV-2, malaria, and mycobacteria serve to illustrate AI's potential for swift and precise diagnosis. Utilization of convolutional neural networks (CNNs) in digital pathology, automated bacterial classification, and colony counting further underscores AI's versatility. Additionally, AI improves antimicrobial susceptibility assessment and contributes to disease surveillance, outbreak forecasting, and real-time monitoring. Despite a few limitations, integration of AI in diagnostic microbiology presents robust solutions, user-friendly algorithms, and comprehensive training, promising paradigm-shifting advancements in healthcare.

Organochlorine pesticides disrupt T helper cell regulation and reduce IL-2 and IFN-γ favoring infection and production of autoantibodies among pemphigus patients.

The list of environmental factors that trigger autoimmune diseases in genetically susceptible individuals has grown in the recent years and is far from complete. The possible intervention of the environment in triggering these diseases is ever more perceived by the clinicians. This study investigated the effect of environmental factors like organochlorine pesticides (OCPs) on proportions of different T lymphocyte subsets and their cytokine secretion in-vitro among pemphigus patients, before and after specific immunosuppressive therapy. Higher levels of OCPs like ß-HCH (isoform of hexachlorohexane), α-endosulfan (a form of endosulfan) and p,p΄-DDE (a metabolite of o,p'-dichlorodiphenyltrichloroethane) were observed in the blood of pemphigus patients as compared to healthy controls. HCH and DDT exposure caused specific reduction in CD8+CD45RA+ and CD4+CD25+ T lymphocyte subpopulations in these patient PBMCs. A strong reduction in Th1 (IL-2 and IFN-γ) cytokines upon exposure to these OCPs in-vitro was also observed. These findings indicate that HCH and DDT have a significant impact on Th1 lymphocytes. Impaired production of these cytokines might favor infections and production of autoantibodies. We therefore speculate that the systemic absorption of the pesticide after the topical contact may be one of the factors triggering the immunological mechanism among pemphigus patients.

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies.

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than -8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.Communicated by Ramaswamy H. Sarma.

Natural and synthetic drugs and formulations for intravaginal HPV clearance.

BACKGROUND: Except for a few preventative Human Papillomavirus (HPV) vaccines, there is currently no cure for HPV infection. There are a number of cutting-edge strategies and potent medications or herbal formulations that can be applied topically for early clearance of HPV infection before HPV DNA gets integrated into host cell genome. This is facilitated due to cervical cancer having distinct and well-recognized long precancerous stages. OBJECTIVES: This review aims to outline every possible medication and formulation, both natural and synthetic, that can be applied topically as intravaginal application to help remove HPV infection at an early precancerous stage. RESULTS: Several anti-HPV/HPV clearance compounds and formulations for high-grade lesions are undergoing clinical trials. However, the majority of compounds are still in the early stages of development and require additional research to become viable HPV clearance candidates. Synthetic drugs may be more promising because they may have a more targeted effect; however, they may also have significant adverse effects. On the other hand, natural medications are safer to use. They are less specific, but have minimal to no adverse effects. CONCLUSIONS: This article may serve as a valuable resource of information for managing and preventing precancerous carcinogenic HPV infections. Research could be directed toward developing candidate drugs to make evidence-based decisions about advancing them to clinical trials and, eventually, to the market for potential use in the prevention and control of cervical cancer, which is almost always preventable or even curable if detected early.

Predictors of Candidemia during Febrile Episode in Lymphoreticular Malignancy Affecting Paediatric Population.

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915-1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value.

Low monocytic HLA-DR expression in critically ill patients of sepsis: An indicator for antimicrobial and/or immunomodulatory intervention.

BACKGROUND: Sepsis is a result of suppressed host immune response which leads to fatal multi-organ dysfunctionality. Low frequency of active monocytes or reduced expression of human leukocyte antigen (HLA)-DR on monocytes shows the suppressed immune response in sepsis patients. One of the well-studied markers in patients with sepsis is procalcitonin (PCT). The role of monocytic (m) HLA-DR expression has been monitored in sepsis and is being considered a marker of the severity of interim immuno-depression in these patients. The study describes the impact of HLA-DR expression on monocytes quantitatively using flow cytometry. METHODS: In this prospective study, we quantified monocytes and their HLA-DR expression in 20 patients of sepsis admitted to the Intensive Care Unit (ICU). Serum levels of PCT and interleukin (IL)-6 production were also measured in these patients, and the results were compared with those in healthy controls. RESULTS: Monocyte frequency calculated was higher in sepsis patients as compared to healthy controls, however, HLA-DR expressing monocytes were significantly reduced as was the mean fluorescence intensity (MFI) of HLA-DR. Contrastingly, IL-6 and PCT levels were significantly high in sepsis than controls. The results suggest that low HLA-DR expression, combined with PCT, is a better prognostic parameter in the early phase of sepsis. CONCLUSION: Poor recovery of mHLA-DR may serve as an early guide for clinicians to assess the prognosis of sepsis patients and consider immunomodulatory therapy in its management.

Incompetent memory immune response in severe COVID-19 patients under treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and declared a Public Health Emergency by the World Health Organization (WHO) on January 30, 2020. Albeit, unprecedented efforts have been made from the scientific community to understand the pathophysiology of COVID-19 disease, the host immune and inflammatory responses are not explored well in the Indian population. Continuous arrival of new variants fascinated the scientists to understand the host immune processes and to eradicate this deadly virus. The aim of this study was to see the helper and cellular host immune responses including memory and activated cell subsets of COVID-19 patients admitted to the intensive care unit (ICU) at different time intervals during the treatment. PBMCs separated from nine patients with SARS-CoV-2 infection were incubated with fluorescent conjugated antibodies and acquired on flow cytometer machine to analyze the T and B cell subsets. The results in COVID-19 patients versus healthy volunteers were as follows: elevated helper T cells (57.4% vs 44.9%); low cytotoxic T cells (42.8% vs 55.6%), and activated T (17.7% vs 21.2%) subsets. Both, TREG (40.15% vs 51.7%) and TH17 (13.2% vs 24.6%) responses were substantially decreased and high expression of TREG markers was observed in these patients compared with controls.