Interaction of tobacco chewing and smoking habit with interleukin 6 promoter polymorphism in oral precancerous lesions and oral cancer.

OBJECTIVE: Our study aims to determine the influence of smoking or tobacco chewing and the association of Interleukin 6 (IL-6) polymorphism, where G is substituted by A at the position - 596 (IL-6 - 596 G/A) and substitution of G by cytosine (C) at position - 572 (IL-6 - 572 G/C) on the susceptibility of precancerous oral lesions and oral cancer. MATERIALS AND METHODS: The participants consisted of 250 subjects among which 75 were suffering from oral cancer, 75 subjects with precancerous oral lesions and 100 were healthy controls. Single-nucleotide polymorphism study (SNP) was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: IL-6 - 596 G/A SNP revealed genotypes, GG, and GA in subjects with precancerous oral lesions and oral cancer, and AA genotype was not found in any subject. IL-6 - 596 G/A was strongly associated with oral precancerous lesions but not with oral cancer. The present study reports that smokers carrying GA for IL-6 - 596 G/A were at several folds higher risk of developing oral precancerous lesions. Smokers with GC and CC for IL-6 - 572 G/C were at higher risk of developing oral precancerous lesions. No significant interaction was observed between these habits and IL-6 - 596 G/A and IL-6 - 572 G/C SNP with oral cancer. CONCLUSION: The interaction of variant A allele of IL-6 - 596 G/A and C allele of IL-6 - 572 G/C polymorphism with smoking and increases the risk of oral precancerous lesions. Tobacco chewing was not related with IL-6 - 596 G/A or IL-6 - 572 G/C in oral precancerous lesions or oral cancer. CLINICAL RELEVANCE: The study will help to determine the susceptibility of individuals with smoking or chewing habits to the development of oral precancerous lesion and oral cancer by monitoring the IL-6 SNPs which can be used as a biomarker for risk determination.

Increased risk of cardiovascular disease in premenopausal female ragpickers of Eastern India: involvement of inflammation, oxidative stress, and platelet hyperactivity.

Millions of poor people in the developing world still thrive on ragpicking. In the present study, we have examined whether ragpicking is associated with increased risk of cardiovascular disease. For this, we have enrolled 112 premenopausal female ragpickers (median age 30 years) and 98 age-matched housemaids as control from Kolkata, Eastern India. Venous blood was drawn for routine hematology; flow cytometry was used to measure generation of reactive oxygen species (ROS) by leukocytes, surface expression of CD62P (P-selectin) in platelets and CD11b in leukocytes. Collagen-induced platelet aggregation was evaluated by aggregometer, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Soluble P-selectin (sP-sel) and CD40L (sCD40L), neutrophil-activating protein-2 (NAP-2), platelet and plasma serotonin, oxidized low-density lipoprotein (oxLDL), and anticardiolipin antibodies (aCL) in plasma were measured by ELISA. Compared with control, the ragpickers had significantly higher prevalence of hypertension and prehypertension, and hypertension was positively associated with ragpicking. The ragpickers also had higher levels of inflammation (elevated NAP-2), oxidative stress (elevated ROS generation with depleted SOD) with oxLDL, platelet activation and aggregability, soluble CD40 ligand, with altered serotonin level (rose in plasma but depleted in platelet). A greater percentage of ragpickers had elevated serum level of aCL of the IgG and IgM isotypes than the controls. The results suggest that the occupation of ragpicking increases the risk of cardiovascular diseases in premenopausal women of Eastern India via inflammation, oxidative stress, platelet hyperactivity, and hypertension.

Respiratory symptoms, lung function decrement and chronic obstructive pulmonary disease in pre-menopausal Indian women exposed to biomass smoke.

BACKGROUND: The impact of chronic exposure to smoke from biomass burning on respiratory health has been examined. METHODS: Six-hundred and eighty-one non-smoking women (median age 35 years) from eastern India who cook exclusively with biomass (wood, dung and crop residues) and 438 age-matched women from similar neighborhood who cook with liquefied petroleum gas (LPG) were examined. Pulmonary function test was done by spirometry. The concentrations of particulate matter having diameter of < 10 µm (PM10) and < 2.5 µm (PM2.5) in indoor air was measured by real-time aerosol monitor. RESULTS: Compared with LPG users, biomass users had greater prevalence of upper (50.9 versus 28.5%) and lower respiratory symptoms (71.8 versus 30.8%) and dyspnea (58.4 versus 19.9%). They showed reduction in all parameters measured by spirometer especially in mid-expiratory volume. PM10 and PM2.5 concentration in biomass using kitchen were 2-3-times more than LPG-using kitchen, and the decline in spirometry values was positively associated PM10 and PM2.5 levels in indoor air after controlling education, family income and kitchen location as potential confounders. Overall, 29.7% of biomass users and 16.4% of LPG users had deficient lung function, and restrictive type of deficiency was predominant. Chronic obstructive pulmonary disease (COPD) was diagnosed in 4.6% of biomass and 0.9% of LPG users. Women who predominantly used dung cake and did not possess separate kitchen had poorer lung function. CONCLUSION: Cumulative exposure to biomass smoke causes lung function decrement and facilitates COPD development even in non-smoking and relatively young pre-menopausal women.

Efficacy and Prolonged Safety of Haemophilus influenzae Type b Conjugate Vaccines.

OBJECTIVE: The purpose of this study was to find data proving the influence of the Haemophilus influenzae type b (Hib) conjugate vaccination on the frequency of invasive Hib illness. METHODOLOGY: A systematic literature search was conducted on the PubMed database to identify peerreviewed publications pertaining to the epidemiology of Haemophilus influenzae meningitis, both before and after the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines. The search query employed a combination of relevant keywords, including "invasive," "Haemophilus," "influenzae," "meningitis," and specific serotype b (Hib). Additionally, terms related to epidemiology, burden, risk factors, impact, Hib vaccine, Hib conjugate vaccine, combination vaccine, vaccine production, efficacy, immunisation coverage, surveillance, review, clinical aspects, outcomes, and various age groups (adults and children) were incorporated. RESULT: The search encompassed articles published till now. Subsequently, relevant research papers concerning Haemophilus influenzae meningitis were subjected to a comprehensive review and analysis. CONCLUSION: The Hib conjugate vaccination has shown to be extremely effective when administered to the entire population. However, changes to the immunisation protocol appear to be required in order to effectively manage invasive Hib illness.

Therapeutic Potential of CRISPR/Cas in Hashimoto's Thyroiditis: A Comprehensive Review.

Hashimoto's thyroiditis (HT) is a commonly occurring illness of autoimmune endocrine origin. It is usually present in the pediatric age group along with other well-known diseases, such as type 1 insulin-dependent diabetes. The defining feature of this disease is the immune-- mediated attack on the thyroid gland resulting in the destruction of thyroid tissues and cells. Given that HT frequently affects family members, it is well-recognized that individuals are genetically predisposed to this disease. Patients with HT also display a significantly increased risk for several different cancers, justifying the eminent need for the development of therapies for managing and treating HT. Gene editing has made several advancements in the field of molecular biology and has turned out to become a promising approach to correct several autoimmune diseases. Currently, CRISPR/Cas, a nuclease-based editing technique, is publicized as a promising tool for curing several genetic diseases and cancers. However, very limited research has been conducted as of now on autoimmune disease management and cure via CRISPR/Cas technique. This review provides an account of the potential candidate genes associated with Hashimoto's thyroiditis, and only a few animal and human models have been generated via the CRISPR/Cas gene editing technique. Mouse models of autoimmune thyroiditis generated through the CRISPR/Cas gene editing technique by targeting the candidate genes will provide us with a deeper insight into the pathophysiology of HT and further pave the way for the immunomodulation of HT via gene editing.

Role of Complement-dependent Cytotoxicity Crossmatch and HLA Typing in Solid Organ Transplant.

BACKGROUND: Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation. METHODS: A systematic literature search was conducted on the internet, using PubMed, Scopus, and Google Scholar databases, to identify peer-reviewed publications about solid organ transplants, HLA typing, and CDC crossmatching. CONCLUSION: Recent advances in HLA typing have allowed for high-resolution evaluation, epitope matching, and personalized therapy methods. Genomic profiling, next-generation sequencing, and artificial intelligence have improved HLA typing precision, resulting in better patient outcomes. Artificial intelligence (AI) driven virtual crossmatching and predictive algorithms have eliminated the requirement for physical crossmatching in the context of CDC crossmatching, boosting organ allocation and transplant efficiency. This review elaborates on the importance of HLA typing and CDC crossmatching in solid organ transplantation.

Role of toll-like receptor in the pathogenesis of oral cancer.

Toll-like receptors are important molecules of innate immunity. They are known as pattern recognition receptors. They recognise certain molecules known as pathogen-associated molecular pattern on a pathogen and release chemicals that causes inflammation. Toll-like receptors (TLR) help in the removal of the infected cell and thus stop the spread of infection and are being studied for their association with cancer. Oral carcinoma has emerged as a major problem of our country today; it is found ranks first in men and third in women. Toll-like receptors have been implicated in the development of cancer. Certain polymorphisms in toll-like receptor can make a cell more susceptible to develop oral cancer. The identification of toll-like receptors and the different genotypes that are involved in the development of cancer can be utilised for using them as biomarkers of the disease. The study revealed that toll-like receptors like TLR7 and TLR5 are found to have a role in suppression of oral cancer while toll-like receptors like TLR4 and TLR2 are found to be associated with the progression of oral cancer. Toll-like receptors can turn out as important target molecules in the future in designing therapeutic strategies for oral cancer.

Matrix Metalloproteinases in Oral Cancer Pathogenesis and their Use in Therapy.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that aid in extracellular matrix (ECM) remodeling. MMPs destroy the extracellular matrix, causing tumor growth and metastasis. MMPs are involved in the spread and metastasis of oral cancer. High levels of MMPs and oral squamous cell carcinoma have been linked to cancer prognosis. Modern medicine aims to prevent the illness from spreading through early intervention and examining changes in MMP genes. MMP gene polymorphism has recently been identified as one of the factors predicting susceptibility or risk in the development of oral carcinoma. This review aims to provide insight into the function of MMP subtypes involved in cancer. The genetic polymorphism in MMP genes and its predictive value in risk evaluation have been elaborated. Novel personalized therapeutic approaches for oral cancer, like the use of MMP inhibitors, nanoparticle-mediated targeting of MMP, or gene silencing by microRNA, can be designed.

Neuronal Vulnerability to Degeneration in Parkinson's Disease and Therapeutic Approaches.

Parkinson's disease is the second most common neurodegenerative disease affecting millions of people worldwide. Despite the crucial threat it poses, currently, no specific therapy exists that can completely reverse or halt the progression of the disease. Parkinson's disease pathology is driven by neurodegeneration caused by the intraneuronal accumulation of alpha-synuclein (α-syn) aggregates in Lewy bodies in the substantia nigra region of the brain. Parkinson's disease is a multiorgan disease affecting the central nervous system (CNS) as well as the autonomic nervous system. A bidirectional route of spreading α-syn from the gut to CNS through the vagus nerve and vice versa has also been reported. Despite our understanding of the molecular and pathophysiological aspects of Parkinson's disease, many questions remain unanswered regarding the selective vulnerability of neuronal populations, the neuromodulatory role of the locus coeruleus, and alpha-synuclein aggregation. This review article aims to describe the probable factors that contribute to selective neuronal vulnerability in Parkinson's disease, such as genetic predisposition, bioenergetics, and the physiology of neurons, as well as the interplay of environmental and exogenous modulators. This review also highlights various therapeutic strategies with cell transplants, through viral gene delivery, by targeting α -synuclein and aquaporin protein or epidermal growth factor receptors for the treatment of Parkinson's disease. The application of regenerative medicine and patient-specific personalized approaches have also been explored as promising strategies in the treatment of Parkinson's disease.

The Impact of Polycystic Ovary Syndrome (PCOS) on the Risk of Developing Ovarian Cancer and Thyroid Disorders: A Comprehensive Review.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women. It is characterized by hyperandrogenism, polycystic ovarian morphology, and other related disorders. It is associated with various health conditions, such as infertility and increased risk of heart problems. Ovarian cancer is also a significant concern, as it is the fifth leading cause of death in women. While there is evidence suggesting a potential association between PCOS and ovarian cancer, the exact nature of this relationship remains unclear. Thyroid disorders, particularly hypothyroidism and Hashimoto's thyroiditis, have also been linked to PCOS. The presence of hypothyroidism can contribute to the development of polycystic ovarian morphology, affecting ovulation and hormone balance. Many works have shown a higher ubiquity of autoimmune thyroid disease in PCOS patients, indicating a potential association between the two conditions. The occurrence of PCOS, hirsutism, and acne underscores the frequency of endocrine disorders in women. This review paper examines the present relevant work on the association between PCOS and ovarian cancer as well as PCOS and thyroid disorders. A systematic literature search was conducted on PubMed, such as PubMed, Scopus, and Google Scholar database, to identify peer-reviewed publications pertaining to PCOS, ovarian cancer, and thyroid disorders. While some studies have delineated a significant link between PCOS and ovarian cancer or thyroid disorders, others have yielded inconclusive results. Further research is necessary to establish a definitive causal relationship between these conditions. Understanding the relationship between PCOS, ovarian cancer, and thyroid disorders is crucial for early detection, accurate diagnosis, and effective management of these conditions. Identifying potential risk factors and developing appropriate screening strategies can improve women's health outcomes and reduce the burden associated with these disorders.

Activation of protein kinase B (PKB/Akt) and risk of lung cancer among rural women in India who cook with biomass fuel.

The impact of indoor air pollution (IAP) from biomass fuel burning on the risk of carcinogenesis in the airways has been investigated in 187 pre-menopausal women (median age 34years) from eastern India who cooked exclusively with biomass and 155 age-matched control women from same locality who cooked with cleaner fuel liquefied petroleum gas. Compared with control, Papanicolau-stained sputum samples showed 3-times higher prevalence of metaplasia and 7-times higher prevalence of dysplasia in airway epithelial cell (AEC) of biomass users. Immunocytochemistry showed up-regulation of phosphorylated Akt (p-Akt(ser473) and p-Akt(thr308)) proteins in AEC of biomass users, especially in metaplastic and dysplastic cells. Compared with LPG users, biomass-using women showed marked rise in reactive oxygen species (ROS) generation and depletion of antioxidant enzyme, superoxide dismutase (SOD) indicating oxidative stress. There were 2-5 times more particulate pollutants (PM(10) and PM(2.5)), 72% more nitrogen dioxide and 4-times more particulate-laden benzo(a)pyrene, but no change in sulfur dioxide in indoor air of biomass-using households, and high performance liquid chromatography estimated 6-fold rise in the concentration of benzene metabolite trans,trans-muconic acid (t,t-MA) in urine of biomass users. Metaplasia and dysplasia, p-Akt expression and ROS generation were positively associated with PM and t,t-MA levels. It appears that cumulative exposure to biomass smoke increases the risk of lung carcinogenesis via oxidative stress-mediated activation of Akt signal transduction pathway.

Relation of vitamin D to COVID-19.

The coronavirus pandemic has lasted for more than a year now and still remains the leading cause of concern, worldwide. The causal agent; SARS- CoV-2, leads to the development of respiratory distress in the lower respiratory tract, sometimes leading to fatalities. Keeping in mind the discovery of mutant strains across the world, as well as the delay in vaccinations across vast populations, most people speculate boosting their immune systems as a preventive and precautionary measure. One of the most commonly observed conditions that hamper immunity; Vitamin D deficiency has been linked to the onset and the alteration of course of the disease in patients and is also being explored as a potential drug supplement. These surmises make it essential to study deep into the speculations. This review aims to overview the possible correlations between Vitamin D and COVID-19.

Recent trends in stem cell-based therapies and applications of artificial intelligence in regenerative medicine.

Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity. This profound potential of stem cells has been thoroughly investigated for its significance in regenerative medicine and has laid the foundation for cell-based therapies. Regenerative medicine is rapidly progressing in healthcare with the prospect of repair and restoration of specific organs or tissue injuries or chronic disease conditions where the body's regenerative process is not sufficient to heal. In this review, the recent advances in stem cell-based therapies in regenerative medicine are discussed, emphasizing mesenchymal stem cell-based therapies as these cells have been extensively studied for clinical use. Recent applications of artificial intelligence algorithms in stem cell-based therapies, their limitation, and future prospects are highlighted.

Alteration in Leukocyte Subsets and Expressions of FcγR and Complement Receptors among Female Ragpickers in Eastern India.

BACKGROUND: There are a million ragpickers in India who gather and trade recyclable municipal solid wastes materials for a living. The objective of this study was to examine whether their occupation adversely affects their immunity. METHODS: Seventy-four women ragpickers (median age, 30 years) and 65 age-matched control housemaids were enrolled. Flow cytometry was used to measure leukocyte subsets, and leukocyte expressions of Fcγ receptor I (CD64), FcγRIII (CD16), complement receptor 1 (CD35) and CR3 (CD11b/CD18), and CD14. Serum total immunoglobulin-E was estimated with enzyme-linked immunosorbent assay. RESULTS: Compared with the controls, ragpickers had significantly (p < 0.0001) higher levels of CD8+T-cytotoxic, CD16+CD56+natural killer, and CD4+CD45RO+memory T-cells, but depleted levels of CD19+B-cells. The percentage of CD4+T-helper-cells was lower than the control group (p < 0.0001), but their absolute number was relatively unchanged (p = 0.42) due to 11% higher lymphocyte counts in ragpickers. In ragpickers, the percentages of CD14+CD16+intermediate and CD14dim CD16+nonclassical monocyte subsets were elevated with a decline in CD14+CD16-classical monocytes. The expressions of CD64, CD16, CD35, and CD11b/CD18 on both monocytes and neutrophils, and CD14 on monocytes were significantly higher in ragpickers. In addition, ragpickers had 2.7-times more serum immunoglobulin-E than the controls (p < 0.0001). After controlling potential confounders, the profession of ragpicking was positively associated with the changes. CONCLUSION: Ragpicking is associated with alterations in both innate (neutrophils, monocytes, and natural killer cell numbers and expression of complement and Fcγ receptors) and adaptive immunity (numbers of circulating B cells, helper, cytotoxic, and memory T cells).

Chronic exposures to cholinesterase-inhibiting pesticides adversely affect respiratory health of agricultural workers in India.

OBJECTIVE: The impact of long term exposure to cholinesterase (ChE)-inhibiting organophosphate (OP) and carbamate (C) pesticides on the respiratory health of agricultural workers in India was investigated. METHODS: Three hundred and seventy-six nonsmoking agricultural workers (median age 41 yr) from eastern India who sprayed OP and C pesticides in the field and 348 age- and sex-matched control subjects with non-agricultural occupations from the same locality were enrolled. Prevalence of respiratory symptoms was obtained by questionnaire survey, and pulmonary function tests were carried out by spirometry. Chronic obstructive pulmonary disease (COPD) was diagnosed by the Global Obstructive Lung Disease (GOLD) criteria, and erythrocyte acetylcholinesterase (AChE) was measured by the Ellman method. RESULTS: Agricultural workers had greater prevalences of upper and lower respiratory symptoms, and appreciable reduction in spirometric measurements. Overall, lung function reduction was noted in 48.9% of agricultural workers compared with 22.7% of control, and a restrictive type of deficit was predominant. COPD was diagnosed in 10.9% of agricultural workers compared with 3.4% of controls (p<0.05 in chi(2) test), and the severity of the disease was greater in agricultural workers. Red blood cell (RBC) AChE was lowered by 34.2% in agricultural workers, and the fall in AChE level was positively associated with respiratory symptoms, lung function decrement and COPD after controlling for education and income as potential confounders. CONCLUSIONS: Long-term exposure to cholinesterase-inhibiting agricultural pesticides currently in use in India is associated with a reduction in lung function, COPD and a rise in respiratory symptoms.

Airway inflammation and upregulation of beta2 Mac-1 integrin expression on circulating leukocytes of female ragpickers in India.

OBJECTIVES: Over one million ragpickers collect and sale recyclable materials from municipal solid wastes (MSW) in India for a living. Since MSW contains a host of pathogenic microorganisms, we investigated the occurrence of airway inflammation and its underlying mechanism in 52 non-smoking female ragpickers (median age 29 yr) and 42 control women matched for age, smoking habit and socioeconomic conditions in Kolkata, eastern India. METHODS: Spontaneously expectorated sputum were stained using the Papanicolau method for cytology, and flow cytometry was used for measurements of surface expression of beta(2) Mac-1 integrin (CD11b/CD18) on leukocytes and P-selectin on platelets. The concentrations of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and chemokine interleukin-8 (IL-8) were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: Compared with controls, sputum samples of ragpickers contained significantly increased numbers of alveolar macrophages, neutrophils, eosinophils and lymphocytes, suggesting airway inflammation. Circulating neutrophils and monocytes of the ragpickers overexpressed CD11b/CD18 and their platelets had upregulated surface expression of P-selectin, implying functional activation of these cells. In addition, plasma levels of IL-8 and TNF-alpha were significantly increased, indicating greater trafficking of leukocytes from circulation to the tissues. Multivariate logistic regression analysis demonstrated a positive association between the ragpicking profession and leukocyte activation after controlling for potential confounders. CONCLUSIONS: Ragpickers experience leukocyte and platelet activation and airway inflammation that could make them more vulnerable to tissue damage and cardiovascular diseases.