Altered TLR7 Expression-Mediated Immune Modulation Is Supportive of Persistent Replication and Intrauterine Transmission of HBV.

Hepatitis B Virus (HBV) is posing as a serious public health threat mainly due to its asymptomatic nature of infection in pregnancy and vertical transmission. Viral sensing toll-like receptors (TLR) and Interleukins (IL) are important molecules in providing an antiviral state. The study aimed to assess the role of TLR7-mediated immune modulation, which might have an impact in the intrauterine transmission of HBV leading to mother to child transmission of the virus. We investigated the expression pattern of TLR7, IL-3, and IL-6 by RT-PCR in the placentas of HBV-infected pregnant women to see their role in the intrauterine transmission of HBV. We further validated the expression of TLR7 in placentas using Immunohistochemistry. Expression analysis by RT-PCR of TLR7 revealed significant downregulation among the Cord blood (CB) HBV DNA positive and negative cases with mean ± standard deviation (SD) of 0.43 ± 0.22 (28) and 1.14 ± 0.57 (44) with p = 0.001. IL-3 and IL-6 expression revealed significant upregulation in the CB HBV DNA-positive cases with p = 0.001. Multinomial logistic regression analysis revealed that TLR7 and IL-3 fold change and mother HBeAg status are important predictors for HBV mother to child transmission. Immunohistochemistry revealed the decreased expression of TLR7 in CB HBV DNA-positive cases. This study reveals that the downregulation of TLR7 in the placenta along with CB HBV DNA-positive status may lead to intrauterine transmission of HBV, which may lead to vertical transmission of HBV.

Occurrence of Existing BCR-ABL Baseline Mutations and Associated Haplotype (NmR) Among CML Patients with Diverse IM Response: A Hospital-based Study from North-East India.

Highly polymorphic BCR-ABL kinase domains have been reported to harbor more than a hundred mutations, and among these, 40-60% have been identified as influencers of imatinib mesylate (IM) resistance. The emergence of IM resistance poses a significant challenge in the management of Chronic Myeloid Leukemia (CML). M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance. During the study period from 2018 to 2022 (48 months), the blood samples from 219 Reverse transcriptase-PCR-confirmed CML patients following RNA extraction and cDNA preparation were subjected to M351T, E255K, and Y253H mutation analysis by PCR-RFLP. After agarose gel visualization, the samples were subjected to Sanger sequencing to confirm the nucleotide change at the polymorphic loci. The wild-type genotype of all three ABL1 SNPs under investigation exhibits a significant reduction in frequency among IM non-responders compared to the responder group. The CGT haplotype frequency exhibits a significant difference between IM responder (4.2%) and non-responder (11.8%) (p = 0.002 < 0.05). Further, CGC haplotype was observed solely among the imatinib non-responder patients with a frequency percentage of 3.3% (p = 0.004), whereas the said genotype was absent among the responder group. A reduced overall survival rate was observed with deviation from wild-type genotype (M351T loci (T > C) with 1.217 times, E255K (G > A) with 1.485 and Y253H (T > C) with 1.399 times increase in hazard ratio) thereby enhancing mortality risk due to disease progression. The significant increase in the frequency of M351T, E255K, and Y253H loci among the IM non-responder group indicated their probable association with the development of IM resistance among CML patients. A haplotype frequency distribution pattern analysis of ABL1 loci further identified the CGC haplotype as an independent predictor for IM resistance. As such the study highlights the importance of patient characteristics, genotype distribution, and haplotype frequency distribution in predicting the response to IM treatment and clinical outcomes of CML patients.

Epigenetic Modulation of DDIT3 and MGMT Expression Acts Synergistically with Resistance to Imatinib towards CML Disease Progression: A Hospital based Study.

INTRODUCTION: Imatinib Mesylate is an authenticated drug that aids in the treatment of Chronic Myeloid Leukaemia and Philadelphia patients which is recognized as a BCR-ABL tyrosine kinase inhibitor. Indeed, DNA Methylation occupies a key role in the stability of chromosomes. OBJECTIVE: Changes in the methylation status of genes may impart to the advancement of Chronic Myeloid Leukaemia. The present investigation aims to assess the role of expression analysis and methylation status of DDIT3 and MGMT genes in imatinib-resistant and nonresistant cases. METHODS: The Imatinib resistance was screened through RFLP. In this case maximum number of patients were recorded in the chronic phase belonging to the age group 40-59 and the accelerated and blast phase is more common in elderly patients showing the progressive nature of the disease with age. Hemoglobin and platelet count are found to be higher in cases where WBC count was minimal. A history of long-term alcohol consumption is found to be associated with the progression of the disease. RESULTS: The maximum level of expression of the DDIT3 gene was recorded in the chronic phase regardless of upstream (67.8%) and downstream (57.9%) regulation. The highest MGMT expression regulation was also observed in the case of chronic phase in both upstream (78.9%) and downstream (44%) regulation. Further, the MGMT gene showed the highest methylation of 6.6% and DDIT3 showed 3.3% in CML cases. CONCLUSION: In the present study notable depletion of survivality was established in the Imatinib resistance patients manifesting genetic malfunction of BCR-ABL transcripts among the North East Indian inhabitants and advocating for the expansion of the disease.

Association of Single Nucleotide Polymorphism in VDR, GC Globulin and CYP2R1 with the Risk of Esophageal Cancer.

BACKGROUND: The proactive role of vitamin D has been well determined in different cancers. The protein that encodes the components of the vitamin D metabolism could appear to play a pivotal role in vitamin D stability and its maintenance. A polymorphism in vitamin-D-receptor (VDR), carrier globulin/binding protein (GC) and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) genes has been predicted to be associated with the development of cancer. This study was designed to detect the association of VDR, GC Globulin and CYP2R1 gene polymorphism with the risk of esophageal cancer in the North-east Indian population. METHODS: To carry out the study, a total of 100 patients diagnosed with esophageal cancer and 101 healthy controls were enrolled. In a case-control manner, all samples were subjected to do genotype testing for known SNPs on the VDR (rs1544410), GC (rs4588), and CYP2R1 (rs10741657) genes using Restriction-fragment length polymorphism (RFLP) followed by Sanger sequencing. The collected demographic and clinical data were analysed using the statistical software package SPSS v22.0. RESULTS: The VDR haplotype heterozygous TC was found strongly associated with the carcinoma group (OR:1.09, 95%CI:0.67-1.75). The risk factors analysis using the GC globulin rs4588 phenotype, found a positive correlation in terms of mutant AA's harmful influence on the cancer cohort (OR = 1.125, OR=1.125, 95% CI, 0.573-2.206). The influence of the CYP2R1 rs10741657 polymorphism on the malignant cohort revealed that the GG mutant had a significant negative influence on the carcinoma, has an influential role in disease severity ( OR:1.736, at 95% CI; 0.368-8.180). CONCLUSION: In conclusion, this study revealed the potential association of VDR gene polymorphism in the progression and development of esophageal cancer in north east Indian population cohort.

Altered Vitamin D Receptor Expression in Apa-I (rs7975232) Allelic Variants-A Probable Risk Factor for Susceptibility to Hepatitis B Virus Infection and Disease Progression.

Vitamin D exerts its antiviral effect through vitamin D receptor (VDR)/retinoid X receptor-mediated host immunomodulation. Besides the downregulation of VDR expression, its polymorphism was also observed among hepatitis B virus (HBV)-positive patients. To understand the possible link between VDR polymorphism and its altered expression during HBV infection and disease progression, VDR Apa-I [rs7975232 (C>A)] single nucleotide polymorphism (SNP) was analyzed in a case-control manner. VDR Apa-I (rs7975232, C>A) polymorphism was studied using 340 HBV patients and 102 healthy controls. Genotype analysis and gene expression study was performed using restriction fragment length polymorphism and quantitative polymerase chain reaction, respectively. Statistical analysis was performed using SPSS (IBM) considering p-value <0.05 as significant for comparing the differences between the groups. Significant mean difference in VDR expression was observed between HBV-positive patients (1.6 ± 0.94) and controls (0.69 ± 0.73). Furthermore, the mean fold change of Healthy control with CC genotype (1.92 ± 0.99) was found to be marginally significant compared with mutant genotype (CA/AA) (1.08 ± 0.43/0.59 ± 0.56, p = 0.045). In HBV+ patients, the mean fold change in the CC genotype was 0.88 ± 0.38, which exhibits a significant mean difference upon comparison with other genotypes (0.52 ± 0.49, 0.113 ± 0.34; p = 0.018, p = 0.048). However, the fold change value does not differ between CA and AA genotypes. Further comparative analysis of VDR expression between the control and case also exhibits significant differences (p = 0.001) among allelic variants. Observed genotype distribution frequency exhibits a significant association with disease type. The mutant genotype was found to be significantly associated with HBV infection and disease progression, (odds ratio = 0.730, 95% confidence interval = 0.462-1.152, p = 0.06). VDR SNP rs7975232 (C>A) may affect VDR expression by controlling several other variables and suggest that deviation from wild-type genotype (CC) is associated with downregulation of expression, which in turn involved in host immunomodulation in favor of HBV infection and disease progression.

Role of inflammasomes and cytokines in immune dysfunction of liver cirrhosis.

Liver cirrhosis develops as a result of persistent inflammation and liver injury. The prolonged inflammation triggers the buildup of fibrous tissue and regenerative nodules within the liver, leading to the distortion of the hepatic vascular structure and impaired liver function. Cirrhosis disrupts the ability of liver function to maintain homeostasis and hepatic immunosurveillance which causes immunological dysfunction in the body. In pathological conditions, the production of cytokines in the liver is carefully regulated by various cells in response to tissue stimulation. Cytokines and inflammasomes are the key regulators and systematically contribute to the development of cirrhosis which involves an inflammatory response. However, the crosstalk role of different cytokines in the cirrhosis progression is poorly understood. Tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), among others, are proinflammatory cytokines that contribute to liver cell necrosis, which in turn causes the development of fibrosis. While IL-10 exhibits a potent anti-inflammatory effect on the liver by inhibiting immune cell activation and neutralizing pro-inflammatory cytokine activity. Inflammasomes have also been implicated in the profibrotic processes of liver cirrhosis, as well as the production of chemokines such as CCL2/MCP-1. It is evident that inflammasomes have a role in the proinflammatory response seen in chronic liver illnesses. In conclusion, cirrhosis significantly impacts the immune system, leading to immunological dysfunction and alterations in both innate and acquired immunity. Proinflammatory cytokines like TNF-α, IL-1ß, IL-6, and IFNγ are upregulated in cirrhosis, contributing to liver cell necrosis and fibrosis development. Managing cytokine-mediated inflammation and fibrosis is a key therapeutic approach to alleviate portal hypertension and its associated liver complications. This review attempted to focus largely on the role of immune dysfunction mediated by different cytokines and inflammasomes involved in the progression, regulation and development of liver cirrhosis.

Altered expression of endosomal Toll-like receptors and HBeAg seropositivity may act synergistically towards the vertical transmission of HBV.

PROBLEM: Hepatitis B is one of the leading causes of mortality in India. Despite the mass vaccination programme, the burden of the infection is still increasing due to its vertical transmission. Asymptomatic nature of hepatitis B virus (HBV) infection owing to immune tolerance among pregnant women is a major issue in this regard. METHOD OF STUDY: As such, this study aims to investigate the potential role of altered Toll-like receptor (TLR) expression (TLR-3, 7 and 9) along with peripheral blood HBeAg status in attaining differential cord blood (CB) HBV DNA status. RESULT: Expression analysis reveals an overall downregulation of expression with mean ± SD value 1.14 ± 1.05, 0.86 ± 0.5 and 0.71 ± 0.4 (TLR 3, 7 and 9, respectively) upon comparison with healthy women. Further stratification based on CB HBV DNA status; the downregulation of expression was found to be significantly (p < .05) associated with positive CB HBV DNA status apart from peripheral HBeAg status. One hundred percent HBeAg positive parturiting women exhibit positive CB HBV DNA. Pearson's correlation analysis reveals a positive correlation between CB HBV DNA status and altered TLR expression, HBeAg status and mother HBV DNA status and as such can be associated with the potential risk of HBV vertical transmission. CONCLUSION: This study suggests that the downregulation of TLR 3, 7 and 9 may be a risk factor for potential vertical transmission of HBV.

Toll-like receptor 2-mediated downstream cytokine levels as determinant of malaria pathogenesis.

Background & objectives: Toll-like receptors (TLRs) are transmembrane proteins that recognize specific molecular patterns and activate downstream cytokine production usually for the eradication of invading pathogens. The objective of this study was to evaluate the genetic polymorphism of TLR2 Arg753Gln (rs 5743708) and soluble cytokines and TLR2 expression levels in malaria disease cases. Methods: The study included prospectively collected 2 ml blood samples from 153 individuals clinically suspected for malaria and confirmed by microscopy and RDT from Assam. Stratification of the study groups was done as healthy control (HC, n=150), uncomplicated malaria (UC-M, n=128) and severe malaria (SM, n=25). The PCR-restriction fragment length polymorphism (RFLP) method was applied for the analysis of TLR2 Arg753Gln polymorphism and following the ELISA for soluble serum TLR2 (sTLR2) and its associated downstream cytokines, viz. tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels. Results: Variation in TLR2 Arg753Gln gene showed no association with the susceptibility and the severity of malarial infection. Soluble TLR2 expression was significantly higher in uncomplicated malaria (UC-M) cases compared to healthy controls (P=0.045) and in terms of SM cases, the expression was also found to be higher in UC-M cases (P=0.078). The TNF-α expression was significantly higher in SM cases compared to both UC-M and control (P=0.003 and P=0.004). Similarly, significantly elevated expression of IFN-γ was noted in SM cases compared to both UC-M (P=0.001) and healthy controls (P<0.001). Interpretation & conclusions: The present study suggests the association of deregulated TLR2 pathway that leads to the deleterious downstream immune response in the development of malarial pathogenicity.

Evaluation and analysis of novel germline variants in ethanol metabolism pathway genes predisposition to liver disease.

The pathogenetic events of liver disease are seemingly determined by factors linked to ethanol metabolism. The variations in genes encoding enzymes of the ethanol metabolic pathway can influence exposure to alcohol and thus may act as risk factors for the development of liver disease. The present study aimed to understand the genetic aspect of germline variations in ethanol metabolic pathway genes in two major categories of liver disease i.e. ALD and NAFLD. Targeted Re-sequencing was performed in the two disease categories along with healthy control followed by an assessment and evaluation of the variants in a case vs control manner. The pathogenicity prediction was evaluated using SIFT, PolyPhen, PROVEN, LRT, CADD, FATHMM, EIGEN, REVEL and VarSome, while MD simulation of a novel significant variant was performed using the GROMACS 5.1.4 package. The annotation of targeted re-sequencing results revealed 2172 variants in different locations of the genes. Upon recurrent assessment predominantly focusing on exonic missense variants from these genes of the alcohol metabolism pathway, the ALDH1L2 [c.337C > G, p.Pro113Ala, (rs199841702)] variant was found highly significant with comprehensive results. The amino acid substitution tool that predicted protein stability due to a point mutation showed a decrease in stability. The genotyping distribution of the identified novel variant in the population revealed that heterozygosity is significantly distributed in ALD patients. However, the predominant association between the inherited variant and the cause of developing disease needs further robust study.

Upregulation of anaphase promoting complex (APC) 7 as a prognostic marker for esophageal squamous cell carcinoma: A hospital based study.

Esophageal cancer is the sixth leading cause of cancer death, and esophageal squamous cell carcinoma (ESCC) is the most prevalent type worldwide, with a poor prognosis due to late diagnosis. The search for new molecular prognostic biomarkers revealed that dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules might lead to perturbed mitotic progression leading to malignancy. We analyzed the expression of the four different subunits of the APC/C complex-APC3, APC4, APC5 and APC7-by Real Time Polymerase Chain Reaction (RT-PCR). The findings were then correlated with clinicopathological parameters and different lifestyle factors. Significant upregulation of APC7 (tissue and blood: N = 50; 3.72 ± 1.21 and 4.45 ± 1.18, respectively) and APC3 (tissue and blood: N = 52 and 55 and 4.50 ± 1.41 and 4.58 ± 1.06, respectively) suggests their role in uncontrolled cell proliferation. In addition to their association with increasing age, their significant association with tumor size, node stage (only APC7 (p < 0.05)), and dysphagia grade supports a potential role in tumorigenic transformation in ESCC. Furthermore, several exclusive lifestyle-associated factors play a crucial supporting role in the development of ESCC in the Northeast Indian population. Various lifestyle factors, such as the duration of smoking, tobacco and betel nut consumption, and the duration of alcohol consumption, are significantly associated with the expression of APC. Analysis based on Pearson's correlation coefficient indicated a positive correlation among the gene expression levels ofAPC3 (both blood and tissue), APC5 (tissue) and APC3 (tissue), APC7 (tissue) and APC3 (tissue), and APC7 (tissue) and APC3 (blood). Additionally, a positive correlation was found between APC7 expression in blood and tissue samples. However, no significant correlation was found between APC 7 expression and APC4 and APC5 expression in either blood or tissue samples.

In-house reverse transcriptase polymerase chain reaction for detection of SARS-CoV-2 with increased sensitivity.

As the COVID-19 infection continues to ravage the world, the advent of an efficient as well as the economization of the existing RT-PCR based detection assay essentially can become a blessing in these testing times and significantly help in the management of the pandemic. This study demonstrated an innovative and rapid corroboration of COVID-19 test based on innovative multiplex PCR. An assessment of optimal PCR conditions to simultaneously amplify the SARS-CoV-2 genes E, S and RdRp has been made by fast-conventional and HRM coupled multiplex real-time PCR using the same sets of primers. All variables of practical value were studied by amplifying known target-sequences from ten-fold dilutions of archived positive samples of COVID-19 disease. The multiplexing with newly designed E, S and RdRp primers have shown an efficient amplification of the target region of SARS-CoV-2. A distinct amplification was observed in 37 min using thermal cycler while it took 96 min in HRM coupled real time detection using SYBR green over a wide range of template concentrations. Our findings revealed decent concordance with other commercially available detection kits. This fast HRM coupled multiplex real-time PCR with SYBR green approach offers rapid and sensitive detection of SARS-CoV-2 in a cost-effective manner apart from the added advantage of primer compatibility for use in conventional multiplex PCR. The highly reproducible novel approach can propel extended applicability for developing sustainable commercial product besides providing relief to a resource limited setting.

Effectual nanotherapy against oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a frequently occurring type of cancer leading loss of huge number of lives. Folic acid (FA) conjugated solid lipid nanoparticle (SLN) loaded paclitaxel (PTX) and ascorbic acid (AA) has been used as a novel approach in this study. METHODS: The FA conjugated SLN were prepared by following high speed homogenization and ultrasonication methods. FA conjugated SLN were used alone and in combination to evaluate their efficacy against OSCC induced animal model. FA conjugated PTX and FA conjugated AA loaded SLN were further subjected to pharmacokinetic and biodistribution. RESULTS: The FA conjugated SLN showed a biphasic drug release behavior both in in vitro as well as in vivo system. FA conjugated PTX loaded SLN and FA conjugated AA loaded SLN shows high efficiency when used in combination as compared to when used individually in vivo. FA conjugated SLN shows a better therapeutic efficacy as compared to normal drug as depicted by the observation of pharmacokinetic and biodistribution studies. CONCLUSION: The in vitro and in vivo evaluation of the FA conjugated SLN concluded with a remark that, these SLN can be effectively used in the treatment of OSCC.

Altered expression of TGF-ß1 and TGF-ßR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma.

In the transforming growth factor ß (TGF-ß) signaling pathway, TGF-ß1 and TGF-ß receptor 2 (TGF-ßR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-ß1 and TGF-ßR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-ß1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-ßR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-ß1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-ßR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-ßR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-ß1 and TGF-ßR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients. *Mean fold change.

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India.

BACKGROUND: Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-ß dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. METHODS: Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR. RESULTS: Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient's tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001). CONCLUSION: The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.

Two novel alleles HLA-DQB1*03:01:01:23 and DQB1*03:01:01:24 in a Konyak Naga individual from North-East India.

HLA-DQB1*03:01:01:07, intron 1 [1217(A→G)] and intron 2 [2138 (T→C)] substitutions generate HLA-DQB1*03:01:01:23 and HLA-DQB1*03:01:01:24, respectively.

Genetic Polymorphisms Along with Dietary and Environmental Factors Enhance the Susceptibility to Nasopharyngeal Carcinoma in Nagaland of Northeast India.

This study investigated the association of seven widely known DNA repair gene polymorphisms (hOGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPC Val499Ala, XPD Lys751Gln and ERCC1 Cys8092Ala) with dietary and environmental factors for Nasopharyngeal Carcinoma (NPC) susceptibility in Nagaland of Northeast India. The genotypes were determined in 128 NPC patients and 180 healthy controls by PCR-RFLP. XRCC1 Arg280His, XPC Val499Ala and ERCC1 Cys8092Ala were found to be associated with NPC risk. Tobacco smoking and burning of firewood for cooking were also found to be a risk factor for NPC. The haplotype analysis of five single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD Lys751Gln and ERCC1 Cys8092Ala identified haplotype TGAAC to be significantly associated with NPC. Multifactor dimensionality reduction (MDR) analysis suggested ERCC1 Cys8092Ala to be the best one-factor model that could predict NPC risk. From this study, we conclude that examining the synergistic interactions of various gene-environmental factors together is a better approach to understand NPC susceptibility, instead of their individual effects.

IL-10 Polymorphisms and Haplotypes Predict Susceptibility to Hepatocellular Carcinoma Occurrence in Patients with Hepatitis C Virus Infection from Northeast India.

Chronic hepatitis C virus (HCV) infection leads to variable outcomes, ranging from prolonged slow hepatic damage leading to cirrhosis, and hepatocellular carcinoma (HCC). Polymorphism in cytokines IL-10 and IL-12 that impact the immune response to HCV infection may play a role in determining this outcome. This study was aimed to determine if polymorphisms in IL-10 and IL-12B contribute to HCV susceptibility and the risk of developing HCC in patients from Northeast India. IL-10 - 1082, -819, -592 polymorphisms and IL-12B -1188 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism in a total of 266 HCV-infected patients and 100 age- and sex-matched controls. In the HCV-infected subjects, 110 patients had chronic hepatitis C (CHC), 96 with liver cirrhosis, and 60 with HCC. Serum levels of IL-10 were also measured and correlated with disease severity. Haplotype analysis for IL-10 polymorphisms was carried out. Statistical data were analyzed using SPSS ver. 22.0. The frequency of IL-10 - 592 AA genotype/A allele was significantly higher in HCC patients than in CHC patients. The intermediate IL-10-producing ACC haplotype was significantly more frequent in HCC and cirrhotic patients than in CHC patients. No significant association was found for IL-10 - 819, -592 and IL-12B -1188 polymorphisms with the susceptibility to HCV infection or occurrence of HCC in HCV-infected patients. IL-10 - 592 CA polymorphism and IL-10 ACC haplotype are significant biomarkers of HCC in HCV-infected patients from Northeast India. Higher serum levels of IL-10 were also linked to higher disease severity.

Antibacterial and nonlinear dynamical analysis of flower and hexagon-shaped ZnO microstructures.

The present study reports the antibacterial properties of flower-shaped ZnO (FZnO) microstructures and its comparison with that of hexagon-shaped bulk ZnO (BZnO) nanostructures. The samples are prepared successfully by wet chemical method and the surface morphologies, structures and size of the ZnO samples are characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), BET adsorption isotherm, and Photoluminescence (PL) Spectroscopy. The SEM and TEM images of the sample have confirmed flower-shaped structure of the ZnO. The materials are also analyzed by using an innovative tool called Lacunarity, a nonlinear dynamical (NLD) tool for proper understanding of the inherent surface properties of the particles formed, comparing the results estimated with the BET results obtained, thereby confirming our proposition to use it as an important parameter in predictive models. In this new approach, geometry of the surface structure is being associated with biological properties, in order to come up with easier ways to identify materials for any such applications where rich surface structure is desired. The photocatalytic activity of the flower-shaped material is carried out to find out its optical properties as another marker for confirming the antimicrobial activities. It has been reported for the first time that the prominent antibacterial activities are favoured by the FZnO microstructure having lesser Lacunarity, significantly better than its bulk counterpart, for inhibiting gram negative - Escherichia coli microorganism.

Detection of the novel HLA-DQB1*03:404 allele in an Ao individual from Nagaland, North-East India.

One nucleotide substitution in codon 127 of HLA-DQB1*03:01:01:07 results in the novel allele, HLA-DQB1*03:404.

A novel allele HLA-B*15:02:01:04, recognized in an individual from the Angami tribe, Nagaland, North-East India.

A single nucleotide change (T to C) in HLA-B*15:02:01:01 results in the novel allele, HLA-B*15:02:01:04.