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.

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.

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.

Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.

Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.

A risk factor-based model for upper aerodigestive tract cancers in India: predicting and validating the receiver operating characteristic curve.

BACKGROUND: A study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing upper aerodigestive tract (UADT) cancers in an Indian population. METHODS: A hospital-based case-control study (n = 480) was conducted in Pune, India. We assessed risk factors for UADT cancers by administering a questionnaire through face-to-face interviews. We developed a risk factor model based on the statistically significant risk factors in multiple logistic regression. A total, single risk score was calculated per individual based on the adjusted odds ratio for each of their risk factors. Standard receiver operator characteristic curve was plotted for the total score and the presence of UADT cancers. The stratification ability of the model was determined using the c-statistic. The optimal criterion value was determined at the point on curve at which the Youden's index was maximal. Confidence intervals were calculated by bootstrapping. RESULTS: Total risk score for each individual ranged from 0 to 26. Area under the receiver operating characteristic curve (95.8; P < 0.001) suggests strong predictive ability. A risk score criterion value of ≤10 produced optimal sensitivity (93.5%), specificity (71.1%), false-positive rate (28.8%), false-negative rate (6.4%), positive predictive value (74.8%), and negative predictive value (96.6%). CONCLUSION: This risk factor-based model has the potential of satisfactorily screening and detection of UADT cancers at its early stage in a high-risk population like India. The identified at-risk individuals can then be targeted for clinical examination and for focused preventive/treatment measures at the hospital.

Global Epidemiology of Head and Neck Cancers: A Continuing Challenge.

BACKGROUND: Head and neck cancers (HNCs) continue to remain a significant public health burden worldwide, causing significant mortality and morbidity despite significant clinical advances enabling their early diagnosis and treatment. METHODS: We used data from the GLOBOCAN 2012, Cancer Incidence in Five Continents, World Health Organization Mortality Database and Surveillance, Epidemiology, and End Results programmes to describe the current epidemiology of HNCs. RESULTS: Estimated age-standardised incidence/mortality rates for cancers of the lip and oral cavity among males and females (7.0/2.3 and 2.6/0.6 per 100,000 per annum) in more developed regions are higher compared to those in less developed regions (5.0/2.8 and 2.5/1.4 per 100,000 per annum). Similarly, the estimated rates for cancers of the tonsils and pharynx among males (7.5/2.5 per 100,000 per annum) and females (2.7/0.5 per 100,000 per annum) are reported to be the highest in Western Europe, whereas these rates for cancer of the larynx among males (7.9/4.0 per 100,000 per annum) and females (0.9/0.5 per 100,000 per annum) are reported to be the highest in the Caribbean. Cancer of the nasopharynx represents a significant HNC burden in the Asia-Pacific region and Northern Africa. CONCLUSION: The current and future estimated burden of HNCs is shifting to less developed regions which may be ill equipped to deal with this increasing burden. This needs urgent attention of policy makers through effective cancer control policy implementation with population-based interventions.

Epigenomics of autoimmune diseases.

Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

Life course models for upper aero-digestive tract cancer.

Upper aero-digestive tract (UADT) cancers are collectively cancers of various human body sites, such as the oral cavity, pharynx, oesophagus and larynx. Worldwide, they are the fourth most frequent cancer type and the fourth most common cause of mortality from cancer. Many studies have shown that several chronic diseases, such as cancer, which occur more commonly in later adulthood, are influenced by social and psychological circumstances during birth, childhood, adolescence and early adult life. It is suggested that the build up of problematic circumstances throughout life is the cause of disease, rather than circumstances that happen at one point in time. UADT cancer is a chronic disease of complex multifactorial origin and most of the underlying exposures/risks cannot be considered as individual factors or in isolation, as they act at different levels, which differ from time to time. Thus, life-course epidemiology, rather than drawing false dichotomies between different risk factors of the underlying disease, attempts to integrate biological and social risk processes that cause the chronic disease. It studies how socially patterned exposures during all stages of life--childhood, adolescence and early adult--influence disease risk in adulthood and socio-economic position and hence may account for social inequalities in adult health and mortality. Furthermore, varying health effects, according to the timing or duration of exposure to socio-economic circumstances, may indicate important traces to the causes of cancer. In this paper, we have attempted to draw a conceptual framework on the relationships between socio-economic inequalities, oral health risk factors along the life-course of an individual and incidence of UADT cancer.

Oral Screening for Pre-cancerous Lesions Among Areca-nut Chewing Population from Rural India.

PURPOSE: To detect early oral premalignant lesions (OPLs) in a rural population chewing tobacco-free areca nut preparations, determine their awareness level of oral cancer and educate them about maintaining good oral health. MATERIALS AND METHODS: A total of 2175 18- to 65-year-old areca nut chewers (male:female ratio 2.5:1), without a history of consuming tobacco in any form, from the villages of two districts of the West Bengal state of India were screened clinically through oral examination for suspected OPLs. A pre-designed questionnaire was employed to record demographic data, information on tobacco-free areca-nut chewing habit and knowledge about oral diseases. Education on oral health was provided through distribution of printed leaflets, display of banner/posters and a public-announcement system. RESULTS: Chewing areca nut in the form of betel quid was more popular (90.7%) than chewing areca nut alone (9%) or tobacco-free packaged areca nut preparation sold as 'pan masala' (0.3%). OPLs were detected in 7.3% of the subjects, more among the males. An increasing incidence of OPLs could be observed with an increase in age as well as with duration and frequency of areca-nut chewing, while decreasing incidence was observed with an increase in educational level. Oral submucous fibrosis showed the highest prevalence (2.7%) among the various OPLs detected. CONCLUSIONS: Tobacco-free areca-nut chewing is an independent risk factor for the development of OPL and a large rural population still practices such high risk behaviour. In rural areas with limited health care resources, screening by visual oral examination involving minimum cost may prove useful to reduce oral cancer mortality.

Changing trends of total knee replacement utilization over more than a decade.

BACKGROUND: Osteoarthritis of the knee causes significant disability amongst the elderly, and total knee replacement remains the only effective intervention for pain relief and functional improvement. Using data from single military healthcare institutional records in India, we estimated the utilization rates of total knee replacement by age, gender and rank profile. METHODS: All the data were retrieved manually from institutional records as the institutional databases are yet to be digitized. The information on the study subjects was retrospectively retrieved from the records of the Department of Orthopaedics from the year 1997 to 2012. Trends were estimated by using two 6-year periods separated by a decade, i.e. 1997-2002 and 2007-2012. We estimated age-, gender- and rank-specific rates of TKR utilization in these years. RESULTS: From 1997 to 2002, 37 TKRs were performed as compared to 800 during 2007-2012, showing a more than 20 times increase. During 1997-2002, the mean age was 62.6 years (SD-9.224) compared to 65.8 years (SD-7.05). There was significant disparity in TKR utilization rates on the basis of rank with officers and their dependent, showing much higher utilization rates in both year groups which is possibly explained by the higher level of awareness about the procedure, higher education levels and higher acceptability of the procedure by the officers as compared to PBORs. The rate of TKR was marginally higher amongst women as compared to men. CONCLUSION: The TKR utilization rates have increased tremendously over a decade. In view of this huge increase, future planning is essential to enable optimal material and human resource allocation as well as training to meet future challenges.

Proviral integration site for Moloney murine leukemia virus (PIM) kinases promote human T helper 1 cell differentiation.

The differentiation of human primary T helper 1 (Th1) cells from naïve precursor cells is regulated by a complex, interrelated signaling network. The identification of factors regulating the early steps of Th1 cell polarization can provide important insight in the development of therapeutics for many inflammatory and autoimmune diseases. The serine/threonine-specific proviral integration site for Moloney murine leukemia virus (PIM) kinases PIM1 and PIM2 have been implicated in the cytokine-dependent proliferation and survival of lymphocytes. We have established that the third member of this family, PIM3, is also expressed in human primary Th cells and identified a new function for the entire PIM kinase family in T lymphocytes. Although PIM kinases are expressed more in Th1 than Th2 cells, we demonstrate here that these kinases positively influence Th1 cell differentiation. Our RNA interference results from human primary Th cells also suggest that PIM kinases promote the production of IFNγ, the hallmark cytokine produced by Th1 cells. Consistent with this, they also seem to be important for the up-regulation of the critical Th1-driving factor, T box expressed in T cells (T-BET), and the IL-12/STAT4 signaling pathway during the early Th1 differentiation process. In summary, we have identified PIM kinases as new regulators of human primary Th1 cell differentiation, thus providing new insights into the mechanisms controlling the selective development of human Th cell subsets.

Identification of early gene expression changes during human Th17 cell differentiation.

Th17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation through genome-wide gene expression profiling. CD4(+) cells isolated from umbilical cord blood were used to determine detailed kinetics of gene expression after initiation of Th17 differentiation with IL1ß, IL6, and TGFß. The differential expression of selected candidate genes was further validated at protein level and analyzed for specificity in initiation of Th17 compared with initiation of other Th subsets, namely Th1, Th2, and iTreg. This first genome-wide profiling of transcriptomics during the induction of human Th17 differentiation provides a starting point for defining gene regulatory networks and identifying new candidates regulating Th17 differentiation in humans.

Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.

Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts.

A Comparative Investigation on Cytokine Expression in Pulmonary Tuberculosis and Comorbidity with Type 2 Diabetes Mellitus.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep understanding of pathophysiology and host-pathogen interaction is essential for early diagnosis and novel drug development. Cytokines play a crucial role in infection and susceptibility, and their expressions could serve as potential biomarkers to enhance our understanding of Mtb pathophysiology for improved therapeutic approaches. This cross-sectional study investigates the levels of four important T-cell immune-mediated cytokines: interleukins (IL-6 and IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha in 80 cohort samples, with 20 people in each group. METHODS: Following proper ethics and patient consent, we collected blood samples and isolated serum from all four groups: TB, type 2 diabetes mellitus (T2DM), type 2 diabetes-TB comorbidity (T2DM + TB), and a healthy individual as a control group (C). Furthermore, cytokine expression was measured in individual serum samples through the enzyme-linked immunosorbent assay method using commercial kits (Diaclone, French). Statistical significance was observed by analyzing triplicate data using t-tests and the one-way ANOVA method with GraphPad Prism 10. RESULTS: The results showed that all four cytokine levels were higher (P ≤ 0.0001) than the control, especially IL-6, IL-10, and IFN-γ, which were found to be upregulated in T2DM + TB samples (P ≤ 0.0001) than individual TB or T2DM samples. CONCLUSION: The high levels of cytokines in comorbidity cases raise the risk of insulin resistance and the severity of TB infection. These levels of expression could be used to keep track of the Mtb infection status or severity, aid in early diagnosis as a possible biomarker, and suggest possible treatment plans.

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.

Oral cancer in India continues in epidemic proportions: evidence base and policy initiatives.

OBJECTIVES: India has the highest number of cases of oral cancer in the world and this is increasing. This burden is not fully appreciated even within India, despite the high incidence and poor survival associated with this disease. Because the aetiology of oral cancer is predominantly tobacco-related, the immense public health challenge can be ameliorated through habit intervention. METHODS: We reviewed current rates of incidence, mortality and survival, and investigated the determinants of disease and current prevention strategies. RESULTS: In addition to tobacco smoking and the myriad other forms of tobacco use prevalent in India, risk factors include areca nut consumption, alcohol consumption, human papillomavirus, increasing age, male gender and socioeconomic factors. Although India has world-leading cancer treatment centres, access to these is limited. Further, the focus of health care services remains clinical and is either curative or palliative. CONCLUSIONS: Although the efforts of agencies such as the Ministry of Health and Family Welfare and the Indian Dental Association are laudable, enhanced strategies should be based on common risk factors, focusing on primary prevention, health education, early detection and the earliest possible therapeutic intervention. A multi-agency approach is required.

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.

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.