Investigating key latent factors influencing alcohol consumption among the tribal male adolescents in Dooars region, West Bengal.

BACKGROUND: Alcohol consumption among tribal male adolescents in India is a significant social concern. Tribal adolescents are particularly vulnerable and tend to lean toward alcohol addiction. Therefore, it is crucial to introduce some necessary footsteps to reduce alcohol consumption. The primary objective of this study is to investigate the association of various latent factors with the alcohol-drinking behavior of tribal adolescents. METHODS: The study collected data from 600 tribal adolescents from the Dooars region, with 241 of them reported consuming alcohol. The study aimed to confirm the theoretical development of hypotheses regarding peer pressure, parental discord, stress, attitude toward alcohol, and food insecurity as exogenous latent factors influencing the alcohol-drinking behavior of tribal adolescents. In this context, the study adopted both measurement and structural models using Partial Least Squares-Structural Equation Modeling (PLS-SEM). RESULTS: The findings revealed a significant path relationship between alcohol drinking behavior and various exogenous factors like peer pressure (ß = 0.214, p = .000), parental discord (ß = 0.121, p = .009), stress (ß = 0.170, p = .000), attitude toward alcohol (ß = 0.110, p = .004), and food insecurity (ß = 0.510, p = .000). This study developed a reflective measurement model, and the evaluation of reflective measurement models was conducted, assessing internal consistency, convergent validity, and discriminant validity, yielding satisfactory results. CONCLUSION: To tackle alcohol issues among tribal adolescents in the Dooars region, effective strategies should be employed. These include educating in schools, highlighting tribal role models, aiding peers with alcohol dependence, providing life skills training, and addressing parental discord and food insecurity through awareness campaigns, workshops, and better infrastructure.

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.

Fine-tuning covalent organic frameworks for structure-activity correlation via adsorption and catalytic studies.

In applications utilizing Covalent Organic Frameworks (COFs) for adsorption, the interplay between crystallinity (vis-à-vis surface area) and active sites still remains ambiguous. To address this, the present study introduces three isoreticular COFs-COP-N18 (covalent organic polymer with short-range order), COF-N18 (COF having long-range order), and COF-N27 (semicrystalline COF with pyridyl heteroatoms)-to explore this duality. Through systematic variations in structural order, pore volume, and pore-wall nitrogen content, we aim to establish a structure-activity relationship (SAR) for these COFs via adsorption and catalysis, using CO2 and I2 as probes. Our investigation highlights the positive influence of crystallinity, surface area, and pore volume in adsorption as well as catalysis. However, the presence of heteroatoms manifests complex behavior in CO2 adsorption and CO2 cycloaddition reactions with epoxides. COF-N18 and COF-N27 showed comparable CO2 uptake capacities at different temperatures (273, 293, and 313 K) and ∼1 bar pressure. Additionally, CO2 cycloaddition reactions were performed with substrates possessing different polarities (epichlorohydrin, 1,2-epoxydodecane) to elucidate the role of COF surface polarity. Further investigation into iodine adsorption was performed to understand the impact of COF structural features on the modes of adsorption and adsorption kinetics. Improvements in COF-crystallinity results in faster average iodine uptake rate at 80% (K80% = 1.79 g/h) by COF-N18. Whereas, heteroatom doping slows down iodine adsorption kinetics (0.35 g/h) by prolonging the adsorption process up to 72 h. Overall, this study advances our understanding of COFs as adsorbents and catalysts, providing key insights into their SAR while emphasizing structural fine-tuning as a key factor for impactful environmental applications.

Revisiting large complex ventral hernia repair: multimodal hybrid technique deploying preoperative Botulinum Toxin A injection, laparoscopic anterior components separation and open mesh repair.

In the past, various techniques had been described to repair large complex ventral hernias. Laparoscopic technique of components separation showed low complication rates and better overall outcome. Recently, Botulinum Toxin A (BTA) has shown benefit in achieving tension-free repair. We describe here our multimodal technique combining BTA injection, laparoscopic anterior components separation (LACS) and open mesh repair. Ten consecutive cases performed over 3 years were studied. A standardised technique was used with a reasonably short learning curve. Patients who generally fit for general anaesthesia were offered surgery after detailed preoperative imaging work up and informed consent. Demographic details, preoperative risk stratification, intraoperative and postoperative outcomes were recorded and analysed. A structured step by step management strategy was adopted. Total ten (n = 10) cases with median age of 42.5 years (range 28-76 years), male to female ratio of 8:2 and median BMI of 32.6 were included. Three patients had pre-existing stomas. Median diameter of hernial defect was 10 cm, IQR 4.8 cm and range of 6-20 cm. No intraoperative or immediate complications were observed. Median hospital stay was 6 days. Two seromas (20%) and two return to theatre (20%) were observed. One recurrence (10%) was observed after median follow-up of 32 months. No 90-day mortality was recorded. Multimodal technique of BTA injection, LACS and midline mesh repair is a reproducible, safe and effective option to repair large complex ventral hernias.

Assessing the modifiable and non-modifiable risk factors associated with multimorbidity in reproductive aged women in India.

BACKGROUND: Reproductive span is the foundation of every woman's health in later life. India is currently facing a growing burden of multiple morbidities among the women in their reproductive age group which may further increase over the coming decades. The purpose of the present study aimed to identify different modifiable and non-modifiable risk factors affecting multimorbidity among the women in reproductive age group in Indian context. METHODS: Secondary data were obtained from the Demography and Health Survey (DHS), conducted in India during 2019-2021. A total of 671,967 women aged 15-49 years were selected for this present study. Descriptive, association studies and multinominal logistic regression analyses were performed to accomplish the objectives. RESULTS: Currently, 6.3% of total study participant's reproductive age group women suffered from multimorbidity in India. Never consuming protein, fruits, vegetables and milk increase the chances of developing multimorbidity. Consumption of fried foods, aerated drinks and addiction towards tobacco and alcohol also has a greater influence on the prevalence of multimorbidity. The prevalence of multimorbidity is sharply increased with increasing age and Body Mass Index (BMI). Regionally, the prevalence of multimorbidity was found more among the women hailed from eastern and north-eastern India. CONCLUSION: To reduce the risk of developing multimorbidity, targeted interventions are needed in the form of educating every woman concerning the importance of having minimum health-related knowledge, maintaining healthy lifestyle, weight management and having proper and balanced diet.

Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates.

The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organisation and dynamics of chromatin compacted by gene-repressing factors are unknown. Using cryo-electron tomography, we solved the threedimensional structure of chromatin condensed by the Polycomb Repressive Complex 1 (PRC1) in a complex with CBX8. PRC1-condensed chromatin is porous and stabilised through multivalent dynamic interactions of PRC1 with chromatin. Mechanistically, positively charged residues on the internally disordered regions (IDRs) of CBX8 mask negative charges on the DNA to stabilize the condensed state of chromatin. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure. In differentiated mouse embryonic stem cells, CBX8-bound chromatin remains accessible. These findings challenge the idea of rigidly compacted polycomb domains and instead provides a mechanistic framework for dynamic and accessible PRC1-chromatin condensates.

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.

Biomimetic Mineralization of Large Enzymes Utilizing a Stable Zirconium-Based Metal-Organic Frameworks.

Enzymes are natural catalysts for a wide range of metabolic chemical transformations, including selective hydrolysis, oxidation, and phosphorylation. Herein, we demonstrate a strategy for the encapsulation of enzymes within a highly stable zirconium-based metal-organic framework. UiO-66-F4 was synthesized under mild conditions using an enzyme-compatible amino acid modulator, serine, at a modest temperature in an aqueous solution. Enzyme@UiO-66-F4 biocomposites were then formed by an in situ encapsulation route in which UiO-66-F4 grows around the enzymes and, consequently, provides protection for the enzymes. A range of enzymes, namely, lysozyme, horseradish peroxidase, and amano lipase, were successfully encapsulated within UiO-66-F4. We further demonstrate that the resulting biocomposites are stable under conditions that could denature many enzymes. Horseradish peroxidase encapsulated within UiO-66-F4 maintained its biological activity even after being treated with the proteolytic enzyme pepsin and heated at 60 °C. This strategy expands the toolbox of potential metal-organic frameworks with different topologies or functionalities that can be used as enzyme encapsulation hosts. We also demonstrate that this versatile process of in situ encapsulation of enzymes under mild conditions (i.e., submerged in water and at a modest temperature) can be generalized to encapsulate enzymes of various sizes within UiO-66-F4 while protecting them from harsh conditions (i.e., high temperatures, contact with denaturants or organic solvents).

The apparent loss of PRC2 chromatin occupancy as an artifact of RNA depletion.

RNA has been implicated in the recruitment of chromatin modifiers, and previous studies have provided evidence in favor and against this idea. RNase treatment of chromatin is commonly used to study RNA-mediated regulation of chromatin modifiers, but the limitations of this approach remain unclear. RNase A treatment during chromatin immunoprecipitation (ChIP) reduces chromatin occupancy of the H3K27me3 methyltransferase Polycomb repressive complex 2 (PRC2). This led to suggestions of an "RNA bridge" between PRC2 and chromatin. Here, we show that RNase A treatment during ChIP causes the apparent loss of all facultative heterochromatin, including both PRC2 and H3K27me3 genome-wide. We track this observation to a gain of DNA from non-targeted chromatin, sequenced at the expense of DNA from facultative heterochromatin, which reduces ChIP signals. Our results emphasize substantial limitations in using RNase A treatment for mapping RNA-dependent chromatin occupancy and invalidate conclusions that were previously established for PRC2 based on this assay.

An association of deficiencies in balanced dietary practices and inadequate iron and folic acid supplement's intake during pregnancy and increasing risk of pre-eclampsia or eclampsia among Indian women.

Pre-eclampsia or eclampsia is a serious reproductive health problem which can cause maternal, fetal and neonatal morbidity and mortality worldwide. However till the notable reasons of it is not very clear at all. The main essence of the present study was to examine the association between dietary intake, iron and folic acid consumption during pregnancy and the chances of occurrences of pre-eclampsia or eclampsia among Indian women. A cross sectional observational study was performed by using NFHS-5 (2019-21) data. 190,797 ever married women aged between 15-49 years who had a live birth in the past five years preceding the survey were availed for this study. Multivariable logistic regression analysis was carried out to find out the association between dietary and supplementary intake and occurrences of eclampsia. About 3.6% of the sample women had pre-eclampsia or eclampsia. The results of the study indicated that the likelihood of the prevalence of pre-eclampsia or eclampsia was significantly higher among those women who did not take adequate diet and as well as not consumed iron and folic acid tablet or syrup for at least 90 days during pregnancy compared to those women who took adequate diet and iron and folic acid supplementation even after controlling some maternal, health and lifestyle, socio-economic and demographic characteristics. Integrated and quality ANC services can only ensure adequate nutritional intake in terms of healthy and balanced diet. So, quality ANC services and with this micronutrients intake could be an effective way to reduce the prevalence of pre-eclampsia or eclampsia.

Age-related anatomical variation and morphometric studies on the optic tectum in post-hatch broiler chicken.

In this investigation the morphological and morphometrical features of the optic tectum in post-hatch broiler chicken were studied macroscopically and microscopically. The present study was conducted on 70 day old broiler chicks which were reared up to 42 days. The whole experimental period of study was divided into seven groups (from group I to VII) at weekly interval (days 0, 7, 14, 21, 28, 35 and 42). The optic lobes were paired and spherical to oval eminences located on the ventro-lateral part of the midbrain in broiler chicken. There was significant increase in length and width of the optic lobes with the advancement of age. Histological analysis of optic tectum shows six basic layers from the external surface to internal one towards the optic ventricle. Different layers of optic tectum were identified as stratum opticum, stratum griseum superficial, stratum griseum central, stratum album central, stratum griseum periventriculare and stratum fibrosum periventriculare with several types of neurons. Among all six layers of the optic tectum the stratum griseum superficial layer showed very high degree of secondry differentiation and evolved into nine sub- layers in all age groups of broiler chickens. Three main cell types had been identified that is, small to medium sized stellate shaped neuron, pyramidal neuron and fusiform neuron, beside these multipolar neuron were also evident. The thickness of all layers of optic tectum significantly increases with the advancement of age of the birds. The optic ventricle was lined with a layer of cuboidal ependymal cells.

Sarcopenia and Osteoporosis.

Osteoporosis and sarcopenia are major health issues which are going to have a significant impact in an aging global population. Osteoporosis, which reduces bone density and increases fracture risk, and sarcopenia, which causes muscle loss and strength loss, have a complicated risk profile with consequences that go beyond bone and muscle health. This chapter illuminates the complex link between osteoporosis and sarcopenia, including overlapping causes, clinical consequences, and new treatments. This chapter covers bone and muscle biology, age-related changes that cause osteoporosis and sarcopenia, and the importance of physical exercise and diet in their prevention and management. It also discusses clinical evaluation methods, risk assessment and diagnostic criteria for early diagnosis and intervention. Novel therapies and continuing research in the management of osteoporosis and sarcopenia are also discussed. Medications, exercise, and nutrition can promote bone and muscle health. This chapter aims to explore the recent concepts by elucidating the complex relationship between osteoporosis and sarcopenia and advocating for integrated care paradigms.

Simple ePDF: A Pair Distribution Function Method Based on Electron Diffraction Patterns to Reveal the Local Structure of Amorphous and Nanocrystalline Materials.

Amorphous, glassy or disordered materials play important roles in developing structural materials from metals or ceramics, devices from semiconductors or medicines from organic compounds. Their local structure is frequently similar to crystalline ones. A computer program is presented here that runs under the Windows operating system on a PC to extract pair distribution function (PDF) from electron diffraction in a transmission electron microscope (TEM). A polynomial correction reduces small systematic deviations from the expected average Q-dependence of scattering. Neighbor distance and coordination number measurements are supplemented by either measurement or enforcement of number density. Quantification of similarity is supported by calculation of Pearson's correlation coefficient and fingerprinting. A rough estimate of fractions in a mixture is computed by multiple least-square fitting using the PDFs from components of the mixture. PDF is also simulated from crystalline structural models (in addition to measured ones) to be used in libraries for fingerprinting or fraction estimation. Crystalline structure models for simulations are obtained from CIF files or str files of ProcessDiffraction. Data from inorganic samples exemplify usage. In contrast to previous free ePDF programs, our stand-alone program does not need a special software environment, which is a novelty. The program is available from the author upon request.

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.

High-Resolution Electron Diffraction of Hydrated Protein Crystals at Room Temperature.

Structural characterization is crucial to understanding protein function. Compared with X-ray diffraction methods, electron crystallography can be performed on nanometer-sized crystals and can provide additional information from the resulting Coulomb potential map. Whereas electron crystallography has successfully resolved three-dimensional structures of vitrified protein crystals, its widespread use as a structural biology tool has been limited. One main reason is the fragility of such crystals. Protein crystals can be easily damaged by mechanical stress, change in temperature, or buffer conditions as well as by electron irradiation. This work demonstrates a methodology to preserve these nanocrystals in their natural environment at room temperature for electron diffraction experiments as an alternative to existing cryogenic techniques. Lysozyme crystals in their crystallization solution are hermetically sealed via graphene-coated grids, and their radiation damage is minimized by employing a low-dose data collection strategy in combination with a hybrid-pixel direct electron detector. Diffraction patterns with reflections of up to 3 Å are obtained and successfully indexed using a template-matching algorithm. These results demonstrate the feasibility of in situ protein electron diffraction. The method described will also be applicable to structural studies of hydrated nanocrystals important in many research and technological developments.

Waste dry cell derived photo-reduced graphene oxide and polyoxometalate composite for solid-state supercapacitor applications.

In the modern era, realizing highly efficient supercapacitors (SCs) derived through green routes is paramount to reducing environmental impact. This study demonstrates ways to recycle and reuse used waste dry cell anodes to synthesize nanohybrid electrodes for SCs. Instead of contributing to landfill and the emission of toxic gas to the environment, dry cells are collected and converted into a resource for improved SC cells. The high performance of the electrode was achieved by exploiting battery-type polyoxometalate (POM) clusters infused on a reduced graphene oxide (rGO) surface. Polyoxometalate (K5[α-SiMo2VW9O40]) assisted in the precise bottom-up reduction of graphene oxide (GO) under UV irradiation at room temperature to produce vanadosilicate embedded photo-reduced graphene oxide (prGO-Mo2VW9O40). Additionally, a chemical reduction route for GO (crGO) was trialed to relate to the prGO, followed by the integration of a faradaic monolayer (crGO-Mo2VW9O40). Both composite frameworks exhibit unique hierarchical heterostructures that offer synergic effects between the dual components. As a result, the hybrid material's ion transport kinetics and electrical conductivity enhance the critical electrochemical process at the electrode's interface. The simple co-participation method delivers a remarkable specific capacity (capacitance) of 405 mA h g-1 (1622 F g-1) and 117 mA h g-1 (470 F g-1) for prGO-Mo2VW9O40 and crGO-Mo2VW9O40 nanocomposites alongside high capacitance retentions of 94.5% and 82%, respectively, at a current density of 0.3 A g-1. Furthermore, the asymmetric electrochromic supercapacitor crGO//crGO-Mo2VW9O40 was designed, manifesting a broad operating potential (1.2 V). Finally, the asymmetric electrode material resulted in an enhanced specific capacity, energy, and power of 276.8 C g-1, 46.16 W h kg-1, and 1195 W kg-1, respectively, at a current density of 0.5 A g-1. The electrode materials were tested in the operating of a DC motor.

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.

Thioxobimanes.

Dioxobimanes, colloquially known as bimanes, are a well-established family of N-heterobicyclic compounds that share a characteristic core structure, 1,5-diazabicyclo[3.3.0]octadienedione, bearing two endocyclic carbonyl groups. By sequentially thionating these carbonyls in the syn and anti isomers of the known (Me,Me)dioxobimane, we were able to synthesize a series of thioxobimanes, representing the first heavy-chalcogenide bimane variants. These new compounds were extensively characterized spectroscopically and crystallographically, and their aromaticity was probed computationally. Their potential role as ligands for transition metals was demonstrated by synthesizing a representative gold(I)-thioxobimane complex.

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.