NCoR1: a key player regulating mycobacterium tuberculosis pathogenesis.

Mycobacterium tuberculosis (Mtb) employs a multifaceted arsenal to elude host defense mechanisms, including those associated with autophagy and lysosome function. Within the realm of host-pathogen interactions, NCOR1, a well-recognized transcriptional co-repressor, is known to associate with a multitude of protein complexes to effect the repression of a diverse spectrum of genes. However, its role in regulating macroautophagy/autophagy, lysosome biogenesis, and, by extension, Mtb pathogenesis remains unexplored. The depletion of NCOR1 assumes a pivotal role in the control of the AMPK-MTOR-TFEB signaling axis, thereby fine-tuning cellular ATP homeostasis. This finely orchestrated adjustment further alters the profile of proteins involved in autophagy and lysosomal biogenesis through its master regulator, TFEB, culminating in the increased Mtb survival within the host milieu. Furthermore, the treatment of NCOR1-depleted cells with either rapamycin, antimycin A, or metformin demonstrates a capacity to restore the TFEB activity and LC3-II levels, consequently restoring the capacity of host cells to clear Mtb. Additionally, exogenous NCOR1 expression rescues the AMPK-MTOR-TFEB signaling axis and essentially the autophagic induction machinery. Overall, these findings demonstrate a crucial role of NCOR1 in regulating Mtb pathogenesis within myeloid cells and sheds light toward its involvement in the development of novel host-directed therapies.

Awareness about Tobacco Causing Head and Neck Cancers via Mass Media: A Case-Control Study from India.

OBJECTIVE: This study aimed to assess the awareness of people about the adverse effects of tobacco (smoking and chewing) consumption causing head and neck cancers (HNCs) via mass media channels like television, cinema, radio and newspapers or magazines, wall painting or billboards / hoardings, public transportation and packets of chewing tobacco, bidis or cigarettes. METHODS: Hospital-based case-control was conducted in Pune, Maharashtra, India. Face to face interviews were conducted for the purpose of data collection on 225 cases and 240 controls. The relationship between two categorical variables were estimated using chi-square test with a  2-tailed P value of <.05.  SPSS software was used for data analysis. RESULTS: Controls as compared to cases had good awareness scores for chewing (59.9%) and smoking tobacco (63.7%), P<0.001. The most common form of mass media was television where the cases (60.4%) and controls (77.9%) had heard messages about tobacco in chewing and smoking form causing HNCs. Level of awareness of tobacco causing HNCs amongst tobacco users, stratified by their status (cases versus controls) showed that cases were 1.68 times less likely than controls to have heard or seen messages about the association between chewing tobacco and HNCs via radio. Males (61.3% and 61.0%) had significantly (P<0.001) more awareness as compared to females (46.9% and 43.5%) about chewing and smoking tobacco as a causal factor for  HNCs. CONCLUSION: Mass media needs to create a social environment which discourages tobacco consumption and promotes oral health at the population level. Additionally, there should be easy access to the availability of support services like Quitline and other community support services.

NCoR1 controls Mycobacterium tuberculosis growth in myeloid cells by regulating the AMPK-mTOR-TFEB axis.

Mycobacterium tuberculosis (Mtb) defends host-mediated killing by repressing the autophagolysosome machinery. For the first time, we report NCoR1 co-repressor as a crucial host factor, controlling Mtb growth in myeloid cells by regulating both autophagosome maturation and lysosome biogenesis. We found that the dynamic expression of NCoR1 is compromised in human peripheral blood mononuclear cells (PBMCs) during active Mtb infection, which is rescued upon prolonged anti-mycobacterial therapy. In addition, a loss of function in myeloid-specific NCoR1 considerably exacerbates the growth of M. tuberculosis in vitro in THP1 differentiated macrophages, ex vivo in bone marrow-derived macrophages (BMDMs), and in vivo in NCoR1MyeKO mice. We showed that NCoR1 depletion controls the AMPK-mTOR-TFEB signalling axis by fine-tuning cellular adenosine triphosphate (ATP) homeostasis, which in turn changes the expression of proteins involved in autophagy and lysosomal biogenesis. Moreover, we also showed that the treatment of NCoR1 depleted cells by Rapamycin, Antimycin-A, or Metformin rescued the TFEB activity and LC3 levels, resulting in enhanced Mtb clearance. Similarly, expressing NCoR1 exogenously rescued the AMPK-mTOR-TFEB signalling axis and Mtb killing. Overall, our data revealed a central role of NCoR1 in Mtb pathogenesis in myeloid cells.

Nanoadjuvants: Promising Bioinspired and Biomimetic Approaches in Vaccine Innovation.

Adjuvants are the important part of vaccine manufacturing as they elicit the vaccination effect and enhance the durability of the immune response through controlled release. In light of this, nanoadjuvants have shown unique broad spectrum advantages. As nanoparticles (NPs) based vaccines are fast-acting and better in terms of safety and usability parameters as compared to traditional vaccines, they have attracted the attention of researchers. A vaccine nanocarrier is another interesting and promising area for the development of next-generation vaccines for prophylaxis. This review looks at the various nanoadjuvants and their structure-function relationships. It compiles the state-of-art literature on numerous nanoadjuvants to help domain researchers orient their understanding and extend their endeavors in vaccines research and development.

Lactobacillus rhamnosus reduces CD8+T cell mediated inflammation in patients with rheumatoid arthritis.

BACKGROUND: The T cells, components of adaptive immunity participate in immune pathology of the autoimmune inflammatory disorder called rheumatoid arthritis (RA). The presence of TLRs on the surface of the CD8+ T cells and their ability to recognize bacterial moieties adds to the inflammatory burden in case of RA. It has been reported that the gut microbiome is necessary for the crucial shift in the balance between proinflammatory and anti-inflammatory cytokines. The altered gut microbiome and the presence of TLRs emphasizes on the microbiome driven inflammatory responses in case of RA. METHODS: Eighty-nine RA patients participated in this study. Clinical variations like disease duration, number of actively inflamed joints, number and type of bone deformities, CRP, RF, Anti-CCP, ESR, DAS 28 score were recorded for each patient. Co-culture of CD8+T cells and bacteria has been performed with proper culture condition. TLRs and inflammatory mediators' expression level were checked by both qPCR and flow cytometry analysis. RESULTS: We observed in the suppression of pro-inflammatory molecules like Granzyme B and IFNƳ and expression of TLR2 in CD8 + T cells upon treatment with Lactobacillus rhamnosus (L. rhamnosus). Moreover, L. rhamnosus activated CD8+T cells such that they could induce FOXP3 expression in CD4+T cells thereby skewing T cell population towards a regulatory phenotype. On the contrary, TLR4 engagement on CD8+T cell by Escherichia coli (E.coli) increased in inflammatory responses following ERK activation. CONCLUSIONS: Thus, we conclude that L. rhamnosus can effectively suppress CD8+T cell mediated inflammation by a simultaneous decrease of Th1 cells that may potentiate better treatment modalities for RA.

Genistein carbon dots exhibit antioxidant and anti-inflammatory effects in vitro.

Genistein, an isoflavone from soybean, has attracted attention due to its health benefits, particularly antioxidant and anti-inflammatory activities. Clinical applications of genistein, however, have been limited due to the considerable hydrophobicity and lower bioavailability of the molecule. In this study, carbon dots (C-dots) synthesized from genistein as the carbonaceous precursor exhibit antioxidant properties in test-tube and cell experiments. Anti-inflammatory activity of the genistein-C-dots was also recorded in LPS stimulated macrophages, manifested in inhibition of pro-inflammatory cytokine levels and enhancement anti-inflammatory cytokine expression. The antioxidant and anti-inflammatory effects of the genistein-C-dots, particularly in comparison to the parent genistein molecules, likely account to the display of functional genistein residues on the C-dots' surfaces, and low band gap energy facilitating electron scavenging. Importantly, the genistein-C-dots featured biocompatibility and low cytotoxicity, underlining their potential as a therapeutic vehicle against inflammatory conditions.

SMRT and NCoR1 fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling.

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by down-regulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) depleted cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT depleted cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

Epigenomics of conventional type-I dendritic cells depicted preferential control of TLR9 versus TLR3 response by NCoR1 through differential IRF3 activation.

Tight control of gene regulation in dendritic cells (DCs) is important to mount pathogen specific immune responses. Apart from transcription factor binding, dynamic regulation of enhancer activity through global transcriptional repressors like Nuclear Receptor Co-repressor 1 (NCoR1) plays a major role in fine-tuning of DC responses. However, how NCoR1 regulates enhancer activity and gene expression in individual or multiple Toll-like receptor (TLR) activation in DCs is largely unknown. In this study, we did a comprehensive epigenomic analysis of murine conventional type-I DCs (cDC1) across different TLR ligation conditions. We profiled gene expression changes along with H3K27ac active enhancers and NCoR1 binding in the TLR9, TLR3 and combined TLR9 + TLR3 activated cDC1. We observed spatio-temporal activity of TLR9 and TLR3 specific enhancers regulating signal specific target genes. Interestingly, we found that NCoR1 differentially controls the TLR9 and TLR3-specific responses. NCoR1 depletion specifically enhanced TLR9 responses as evident from increased enhancer activity as well as TLR9-specific gene expression, whereas TLR3-mediated antiviral response genes were negatively regulated. We validated that NCoR1 KD cDC1 showed significantly decreased TLR3 specific antiviral responses through decreased IRF3 activation. In addition, decreased IRF3 binding was observed at selected ISGs leading to their decreased expression upon NCoR1 depletion. Consequently, the NCoR1 depleted cDC1 showed reduced Sendai Virus (SeV) clearance and cytotoxic potential of CD8+ T cells upon TLR3 activation. NCoR1 directly controls the majority of these TLR specific enhancer activity and the gene expression. Overall, for the first time, we revealed NCoR1 mediates transcriptional control towards TLR9 as compared to TLR3 in cDC1.

Toll-like receptor-7 activation in CD8+ T cells modulates inflammatory mediators in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology with aberrant immunological responses leading to inflammation, swelling and pain of the joints. CD8+ T cells have been known to be one of the major immune modulators in the progression of RA and the presence of toll-like receptors (TLRs) on these cells further accentuate their role in RA. Herein, we report an increased expression of TLR7 in the endosomes of CD8+ T cells of RA patients correlating with disease severity. The stimulation of TLR7 with Imiquimod (IMQ) in these CD8+ T cells drives the signalling cascade via NFkB and pERK activation and hence an increase in the mRNA transcripts of signature cytokines and cytolytic enzymes. However, a parallel synthesis of Tristetraprolin (TTP), an mRNA destabilizing protein prevents the translation of the mRNA transcripts, leading to a rapid degeneration of the target mRNA. We thus report that a direct TLR7 ligation by its agonist increases cytokine transcript signature but not an equivalent protein surge.

Understanding the Role and Uses of Alternative Therapies for the Management of Rheumatoid Arthritis.

With the growing popularity of complementary and alternative medicine (CAM) among individuals with chronic pain and muscular problems, a number of patients with rheumatoid arthritis (RA) show their interest in CAM interventions for disease improvement. Various reports published on CAM are based on an animal model of RA; however, there is often a lack of high-quality clinical investigations for explaining the success stories of CAM therapies in patients with RA. CAMs having the potential to be used for therapy in patients with RA have been identified, however lack of awareness and skepticism of their efficacy has made the patients reluctant to choose these drug-less therapies. In this review, we have summarized the existing evidence which suggests promising efficacy of different alternative therapies in managing RA and providing both physical and mental well-being to RA patients.

Delayed Tibial Shaft Fracture Healing Associated with Smoking: A Systematic Review and Meta-Analysis of Observational Studies Conducted Worldwide.

Tibial fractures represent a great burden of disease globally, being the most common long-bone fracture; smoking is a known risk factor for delayed skeletal healing and post-fracture complications. This systematic review and meta-analysis aims to analyse the effect of smoking on healing of tibial shaft fractures. PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched from inception to March 2021, with no limitation on language, to find relevant research. All observational studies that assessed the association between cigarette smoking and tibial shaft fracture healing in adults (≥18 years) were included. The quality of studies was evaluated using the Newcastle Ottawa Quality Assessment Scale. A random effects model was used to conduct meta-analysis. Tobacco smoking was associated with an increased rate of non-union and delayed union as well as an increase in time to union in fractures of the tibial shaft. Among the 12 included studies, eight reported an increased rate of non-union, three reported delayed union, and five reported an increase in time to union. However, the results were statistically significant in only three studies for non-union, one for delayed union, and two studies for increased time to union. This review confirms the detrimental impact of smoking on tibial shaft fracture healing and highlights the importance of patient education regarding smoking cessation.

The COVID-19 pandemic: an increased risk of rheumatoid arthritis.

COVID-19 is a respiratory infection similar to viral pneumonia and is caused by SARS-CoV-2. Chloroquine and hydroxychloroquine make up the major part of the treatment regimen for the management of COVID-19 infections, which are also commonly used in treatment of patients with malaria as well as autoimmune diseases like rheumatoid arthritis (RA). In this review, we analyzed the scientific evidences pertaining to any possible association of SARS-CoV-2 infection with RA. We thus believe that people predisposed to RA carry a higher infection risk than the general population both due to the iatrogenic effects of the RA related drug therapy. Thus COVID-19 pandemic may bring a higher risk of health emergency in complex diseases such as RA.

Impact of COVID-19 pandemic on orthopaedic surgeons in terms of anxiety, sleep outcomes and change in management practices: A cross-sectional study from India.

PURPOSE: The aim of this study was to assess the effects of the COVID-19 pandemic on anxiety, sleep outcomes and change in clinical management practices among orthopaedic surgeons following a nation-wide lockdown. METHODS: We conducted an online cross-sectional study using piloted structured questionnaires with self-reported responses from Indian orthopaedic surgeons. Study participants were identified through social networking sites: Facebook and WhatsApp. The extent of anxiety and sleep quality was assessed by the standardised seven-item Generalised Anxiety Disorder (GAD-7) scale, single-item sleep quality scale, questions on unavailability of personal protective equipment, training module on COVID-19 and change in orthopaedic patient management. RESULTS: One hundred male orthopaedic surgeons responded to the survey with majority (79%) in 30-44 years age group. Severe anxiety scores were observed in 8%; moderate, mild and minimal anxiety was observed in 12%, 27% and 53% surgeons respectively. Changes in management practice due to the pandemic was admitted by 65% respondents. We also observed an association between higher anxiety among surgeons and primary or secondary level of healthcare facility: (p = 0.04). Sleep disturbance was significantly associated with change in management practice to non-operative procedures (p = 0.03). CONCLUSION: Anxiety among orthopaedic surgeons during the COVID-19 pandemic is related to factors like younger age group, working in a primary or secondary healthcare facility. Early recognition of anxiety is essential to prevent serious psychological sequelae.

Changes in Tobacco Use Patterns during COVID-19 and Their Correlates among Older Adults in Bangladesh.

The present study explored the changes in tobacco use patterns during the COVID-19 pandemic and their correlates among older adults in Bangladesh. This cross-sectional study was conducted among 1032 older adults aged ≥60 years in Bangladesh through telephone interviews in October 2020. Participants' characteristics and COVID-19-related information were gathered using a pretested semi-structured questionnaire. Participants were asked if they noted any change in their tobacco use patterns (smoking or smokeless tobacco) during the COVID-19 pandemic compared to pre-pandemic (6 months prior to the survey). Nearly half of the participants (45.6%) were current tobacco users, of whom 15.9% reported increased tobacco use during the COVID-19 pandemic and all others had no change in their tobacco use patterns. Tobacco use was significantly increased among the participants from rural areas, who had reduced communications during COVID-19 compared to pre-pandemic (OR = 2.76, 95%CI:1.51-5.03). Participants who were aged ≥70 years (OR = 0.33, 95% CI: 0.14-0.77), widowed (OR = 0.36, 95% CI: 0.13-1.00), had pre-existing, non-communicable, and/or chronic conditions (OR = 0.44, 95% CI: 0.25-0.78), and felt themselves at the highest risk of COVID-19 (OR = 0.31, 95% CI: 0.15-0.62), had significantly lower odds of increased tobacco use. Policy makers and practitioners need to focus on strengthening awareness and raising initiatives to avoid tobacco use during such a crisis period.

Increased Extracellular ATP in Plasma of Rheumatoid Arthritis Patients Activates CD8+T Cells.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with genetic and environmental causes often linked with the disease etiology. A disrupted metabolism has often been a characteristic of RA and an altered metabolic state of immune cells has been associated with their phenotypic and functional changes. The energy in the form of ATP produced by the metabolically active cells may thus initiate a cascade of immune responses there by influencing the disease pathogenesis or progression. AIM OF THE STUDY: Through this study we have focused on determining the role of ATP in etiology of RA and aberrant cellular functions. METHODS: Blood samples of 80 healthy controls (HC) and 95 RA patients were screened for extracellular ATP concentration, transcriptome analyses, an inflammatory mediator and the results were statistically analysed. RESULTS: In this study, ATP is shown to be excessive in the plasma of RA patients (453.5 ± 16.09% in RA vs. 233.9 ± 10.07% in HC, p <0.0001) and significantly increases with the disease severity. The abundant extracellular ATP could activate circulating cytotoxic CD8+T cells in RA patients to produce Granzyme B. CONCLUSION: Plasma ATP is thus identified to have a significant potential in progression and prognosis of RA and may thus be studied further to design better therapeutic approaches for the disease.

Differential mitochondrial genome in patients with Rheumatoid Arthritis.

BACKGROUND: Mitochondria play an important role in cell survival, function and lineage differentiation. Changes in mitochondrial DNA (mtDNA) may control mitochondrial functions and thus may impart an alternative cellular state thereby leading to a disease condition in the body. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease wherein immune cells become self-reactive causing joint inflammation, swelling and pain in patients. The changes in mtDNA may alter cellular functions thereby directing the immune cells towards an inflammatory phenotype in RA. Therefore, it becomes pertinent to identify changes in mtDNA sequence in immune cells of RA patients to understand the pathogenesis and progression of RA. METHODS: mtDNA from peripheral blood mono-nuclear cells (PBMCs) of 23 RA patients and 17 healthy controls (HCs) were sequenced using next-generation sequencing (NGS). Further, single nucleotide polymorphisms (SNPs) and other variable changes in mtDNA hypervariable and coding regions, amino acid changes with a putative impact on disease, levels of heteroplasmy, copy number variations and haplogroup analysis in RA patients and HCs were analysed and compared to identify any association of mtDNA changes and RA disease. RESULTS: A total of 382 single nucleotide mtDNA variants were observed, 91 (23.82%) were present in hypervariable region and 291 (76.18%) in coding region of patients and HC. The variant 513 GCA > ACA, with G present in HVR-III, known to control the mitochondrial translation function, was significantly present in RA patients. The CYTB gene had larger number of SNPs in HC samples while RNR2 was more variable in RA patients. A non-synonymous heteroplasmy in ND1 gene was found at a single nucleotide position 3533 in an increased number of RA patients as compared to the controls. A significant increase in mtDNA duplication and a higher frequency of the haplogroup U was also characteristic of RA. Also, the presence of SNPs in mitochondrial tRNA genes at two positions 12308 A > G and 15924 A > G were found to be pathogenic. CONCLUSION: We herein observed an altered mtDNA sequence in immune cells of RA patients and thus a possible role of mitochondrial genome in the development of RA. The observed nucleotide changes in mtDNA control region, RNR2 gene, increased heteroplasmy and mtDNA duplication in RA patients may alter sites for transcription factor binding thereby influencing mtDNA gene expression, as well as copy numbers thereby affecting the mitochondrial proteins and their functions. These changes in mtDNA could be one of the probable reasons among many leading to the progression of RA.

Anxiety and Sleep Disturbances Among Health Care Workers During the COVID-19 Pandemic in India: Cross-Sectional Online Survey.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has become a serious concern among the global medical community and has resulted in an unprecedented psychological impact on health care workers, who were already working under stressful conditions. OBJECTIVE: In this study, we aimed to evaluate and measure the effects of the COVID-19 pandemic on the anxiety levels and sleep quality among health care workers in India, as well as to determine how the unavailability of personal protective equipment affects their willingness to provide patient-related care. METHODS: We conducted an online cross-sectional study using piloted, structured questionnaires with self-reported responses from 368 volunteer male and female health care workers in India. Study participants were identified through social networking platforms such as Facebook and WhatsApp. The survey evaluated the participants' degree of signs and symptoms of anxiety and sleep quality based on the 7-item Generalized Anxiety Disorder (GAD-7) scale and single-item Sleep Quality Scale, respectively. Information on the availability of personal protective equipment was collected based on responses to relevant survey questions. RESULTS: The majority of health care workers (126/368, 34.2%) were in the age group 45-60 years, and 52.2% (192/368) were doctors. Severe anxiety (ie, GAD-7 score >10) was observed among 7.3% (27/368) health care workers, whereas moderate, mild, and minimal anxiety was observed among 12.5% (46/368), 29.3% (108/368), and 50.8% (187/368) health care workers, respectively. Moreover, 31.5% (116/368) of the health care workers had poor-to-fair sleep quality (ie, scores <6). Univariate analysis showed female gender and inadequate availability of personal protective equipment was significantly associated with higher anxiety levels (P=.01 for both). Sleep disturbance was significantly associated with age <30 years (P=.04) and inadequate personal protective equipment (P<.001). Multivariable analysis showed that poorer quality of sleep was associated with higher anxiety levels (P<.001). CONCLUSIONS: The COVID-19 pandemic has potentially caused significant levels of anxiety and sleep disturbances among health care workers, particularly associated with the female gender, younger age group, and inadequate availability of personal protective equipment. These factors put health care workers at constant risk of contracting the infection themselves or transmitting it to their families. Early identification of at-risk health care workers and implementation of situation-tailored mitigation measures could help alleviate the risk of long-term, serious psychological sequelae as well as reduce current anxiety levels among health care workers.

NCoR1 fine-tunes type-I IFN response in cDC1 dendritic cells by directly regulating Myd88-IRF7 axis under TLR9.

Plasmacytoid dendritic cells (DCs) are reported to induce robust type-I interferon (IFN) response, whereas cDC1 DCs develop moderate type-I IFN response upon TLR9 stimulation. It is very interesting to understand how this signaling under TLR9 is tightly regulated for the induction of type-I IFNs. Here, we report co-repressor protein NCoR1 as the major factor fine-tuning the signaling pathways regulating IFN-ß expression under TLR9 in cDC1 DCs. We found that NCoR1 knockdown induced a robust IFN-ß-mediated antiviral response upon TLR9 activation in cDC1 DCs. At the molecular level, we showed that NCoR1 directly repressed MyD88-IRF7 signaling axis in cDC1 cells. Therefore, NCoR1 depletion enhanced pIRF7 levels, IFN-ß secretion, and downstream pSTAT1-pSTAT2 signaling, leading to sustained induction of IFN stimulatory genes. Integrative genomic analysis depicted strong enrichment of an antiviral gene-module in CpG-activated NCoR1 knockdown DCs upon TLR9 activation. Moreover, we confirmed our findings in primary DCs derived from splenocytes of WT and NCoR1 DC-/- animals, which showed protection from Sendai and Vesicular Stomatitis viruses upon CpG activation. Ultimately, we identified that NCoR1-HDAC3 complex is involved in repressing the type-I IFN response in cDC1 DCs.

Altered mitochondrial proteome and functional dynamics in patients with rheumatoid arthritis.

The autoimmune inflammatory disease, Rheumatoid arthritis (RA), has known imbalances in energy metabolism and superoxide levels thus may have an etiology associated with mitochondrial dysfunction. We thus evaluated the presence of a differential mitochondrial proteome as well as other characteristics including mitochondrial mass, membrane potential (Ψm), total cellular ATP and superoxide levels. Eighteen mitochondrial proteins were down-regulated while four were up-regulated in RA patients in comparison to the healthy controls (HC). A significant decrease in mitochondrial Ψm, superoxides and cellular ATP levels was observed in RA with constant mitochondrial mass suggesting mitochondrial dysfunction responsible for functional disparity in RA.

Periodontitis, oral hygiene habits, and risk of upper aerodigestive tract cancers: a case-control study in Maharashtra, India.

OBJECTIVE: Chronic destructive periodontitis, a cause of systemic inflammation, affects some 10% to 15% of adults across the globe, with severity of disease increasing with age. The aim of this study was to explore the relationship between periodontitis and oral hygiene habits and upper aerodigestive tract (UADT) cancers. STUDY DESIGN: We conducted a case-control study, which included 240 UADT cancer cases and 240 controls matched by gender and age (±5 years) from 2 different hospitals in Pune, India. In-person interviews and intraoral examinations were conducted for all patients. RESULTS: Severe periodontitis and greater than 5 missing teeth were associated with a significant risk of UADT cancers (adjusted odds ratio [OR] 2.25, 95% confidence interval [CI] 1.12-4.91; adjusted OR 3.28, 95% CI 1.95-5.49). Among the self-reported oral hygiene habits, dental checkups only at the time of pain was associated with an elevated risk for UADT cancers (adjusted OR 4.12; 95% CI 2.63-6.47). Topical application of mishri (black powder obtained by roasting and grinding tobacco) on gums (adjusted OR 3.06; 95% CI 1.75-5.35) and toothbrushing frequency less than once daily; (adjusted OR 2.09; 95% CI 1.27-3.45) were also associated with an elevated risk. Furthermore, the habit of ever chewing tobacco was associated with an elevated risk of severe periodontitis. CONCLUSIONS: Severe periodontitis is associated with an elevated risk for UADT cancers, and tobacco chewing strengthens this association in this population.