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Due to the great success of hypergeometric functions, we provide the analytical solutions of certain definite logarithmic integrals and Nielsen-type integrals in terms of multi-variable Kampé de Fériet functions with suitable convergence conditions and higher harmonic sums by using series rearrangement technique and incomplete Gamma function. Further we also obtain the solution of other related logarithmic integrals in terms of generalized hypergeometric functions and Kummer’s confluent hypergeometric functions by using series rearrangement technique. The results presented in the paper and comparable outcomes are hoped to be supplied by the use of computer-aid programs, for example, Mathematica. [ABSTRACT FROM AUTHOR]

Owing to the remarkable success of the hypergeometric functions of one variable, the authors present a study of some families of hypergeometric functions of two or more variables. These functions include (for example) the Kampé de Fériet-type hypergeometric functions in two variables and Srivastava’s general hypergeometric function in three variables. The main aim of this paper is to provide several (presumably new) transformation and summation formulas for appropriately specified members of each of these families of hypergeometric functions in two and three variables. The methodology and techniques, which are used in this paper, are based upon the evaluation of some definite integrals involving logarithmic functions in terms of Riemann’s zeta function, Catalan’s constant, polylogarithm functions, and so on. [ABSTRACT FROM AUTHOR]

A new technique based on adaptive multi-resolution image decomposition (AMID) using adaptive thresholding for ultrasound speckle reduction has been proposed in this paper. The noisy image is first filtered to reduce large multiplicative noise. The image is then log-transformed before decomposing it to its approximation and detailed coefficients using AMID algorithm. The approximation coefficients are appropriately filtered while adaptive thresholding is applied to the detail coefficients. The image is reconstructed back from all the modified coefficients to obtain the denoised image. This method combining adaptive decomposition with adaptive thresholding makes it adaptive to both signal and noise components, thereby retaining the edge details in the denoised image effectively. The proposed technique performance is tested on synthetic as well as real ultrasound images with the noise of different variances. The experimental results show that the proposed algorithm gives better performance than the other state-of-the-art methods in terms of edge keeping index (EKI), correlation coefficient (CC), figure of merit (FOM), peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and signal-to-noise ratio (SNR) for synthetic images. The algorithm gives better performance in terms of equivalent number of looks (ENL) and mean-to-variance ratio (MVR) for real ultrasound images. [ABSTRACT FROM AUTHOR]

Background- Antenatal depression is affecting 10% pregnant women worldwide with higher prevalence in developing countries. This causes poor maternal and foetal outcome and also affects cognitive development of the child. Aim and objective: To estimate magnitude of antenatal depression and its risk factors. Methodology- A cross-sectional survey was done at the antenatal clinic of community health department catering to an urban resettlement colony, East Delhi. Estimated sample size was 216 (including 10% non-response rate). Pregnant women attending the ANC clinic from October 2019 to February 2020 were enrolled. EPDS questionnaire was used to assess depression during pregnancy. Results-The antenatal depression was found in 11.8% subjects as per EPDS score. Working female and belonging to Muslim religion, past history of abortion, complications in previous pregnancy, financial debt, physical violence and substance use in family showed significant association with antenatal depression. Conclusion --Depression was prevalent among antenatal women and was found to be associated with various risk factors. [ABSTRACT FROM AUTHOR]

An extension of slant Hankel operator, namely, the k-th-order λ-slant Hankel operator on the Lebesgue space L2(Tn)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$L^{2}(\mathbb{T}^{n})$$\end{document}, where T\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\mathbb{T}$$\end{document} is the unit circle and n ≥ 1, a natural number, is described in terms of the solution of a system of operator equations, which is subsequently expressed in terms of the product of a slant Hankel operator and a unitary operator. The study is further lifted in Calkin algebra in terms of essentially k-th-order λ-slant Hankel operators on L2(Tn)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$L^{2}(\mathbb{T}^{n})$$\end{document}. [ABSTRACT FROM AUTHOR]

In this paper, the commutative and spectral properties of a kth-order slant Hankel operator (k ≥ 2, a fixed integer) on the Lebesgue space of n-dimensional torus, T n , where T is the unit circle, are studied. Characterizations for the commutativity and essential commutativity between higher order slant Hankel operators and slant Toeplitz operators have been obtained. The presence of an open disk in the point spectrum of a kth-order slant Hankel operator with a unimodular inducing function has also been ensured. [ABSTRACT FROM AUTHOR]

In this paper, we generalize the concept of asymptotic Hankel operators on H 2 (D) to the Hardy space H 2 (D n) (over polydisk) in terms of asymptotic Hankel and partial asymptotic Hankel operators and investigate some properties in case of its weak and strong convergence. Meanwhile, we introduce ith-partial Hankel operators on H 2 (D n) and obtain a characterization of its compactness for n > 1. Our main results include the containment of Toeplitz algebra in the collection of all strong partial asymptotic Hankel operators on H 2 (D n) . It is also shown that a Toeplitz operator with symbol ϕ is asymptotic Hankel if and only if ϕ is holomorphic function in L ∞ (T n) . [ABSTRACT FROM AUTHOR]

In this paper, a system of partial differential equations describing an inviscid, one dimensional, self-gravitating and spherically symmetric interstellar gas cloud is considered. An infinite set of transport equations is obtained by using the method based on the kinematics of one dimensional motion of shock waves. A truncation procedure is used to put an end to infinite hierarchy of equations. The first three truncated equations (i.e. zeroth, first and second orders) describing shock strength and the induced discontinuities are considered and used to study the growth and decay of shock waves in the medium. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Design: A prospective cross-sectional study with convenience sampling approach was done to assess quality of life (QoL) in 100 soldiers and veterans affected by spinal cord injury (SCI). Purpose: SCI affects almost every aspect of the life of an affected individual. This study was done to measure the impact of SCI on QoL of affected soldiers and veterans using the WHOQOL-BREF questionnaire. Overview of Literature: The devastating effect of SCI on QoL is well known. However, this study is unique in that it includes soldiers and veterans, who constitute a large, but excluded, cohort in most demographic studies. Methods: A cross-sectional study was done at two SCI rehabilitation centres of the Indian armed forces. Data was collected by faceto- face interviews from 100 patients, which included both sociodemographic data as well as all the questions included in WHOQOLBREF questionnaire. Statistical analysis was performed using SPSS software. Results: Age and marital status did not have any influence on QoL. Level of injury (paraplegic or quadriplegic), level of education and presence of other medical co-morbidities had the most significant influence on QoL. Presence of other medical co-morbidities had a negative influence on QoL. Conclusions: Identification of factors having a positive and negative influence on QoL help in formulating measures and policies that positively influence the QoL following SCI in soldiers. Future longitudinal studies with larger sample sizes and assessment of additional variables in addition to WHOQOL-BREF, like presence/absence of secondary complications, are required to bring about policy changes to provide SCI patients with additional support and increased access to equipment or lifestyle interventions. [ABSTRACT FROM AUTHOR]

Introduction: Extreme hot climatic conditions constitute a major public health threat. Recent studies have shown higher rate of perioperative complications during hot weather. Although a lot of researches have been carried out to evaluate effect of hot climatic conditions and its correlation with other medical conditions, but very little has been studied in trauma patients. Aim: To evaluate the impact of hot climatic conditions on perioperative morbidity in trauma patients. Materials and Methods: We enrolled 100 trauma patients scheduled for surgery after approval by the Hospital and University Ethical Committee. Patients were grouped as Control Group (C) when outdoor temperature ranged in comfortable zone i.e., 20-29°C and Study Group (S) when outdoor temperature ranged 40°C or more. Patients living in regular air conditioned atmosphere (more than 18 hours per day) and with co-morbid conditions or on drugs interfering with temperature regulation were excluded. Student's t-test, z-test and chi-square tests were used for statistical analysis. Results: Both groups were comparable in terms of demographics, age (control group C=38.2±12.93 years and in group S= 40.14 ± 15.98 years), sex, socioeconomic status and type of surgery. Mean Trauma Index Score (TIS) were 6.20±1.56 and 5.80±1.31 respectively. All patients were of low risk as per Shoe Maker's risk criteria. Post Anaesthesia Care Unit (PACU) stay was similar. Mean duration of hospital stay was 12.16 ± 8.50 days in group C and 10.98 ± 6.90 days in group S (p-value 0.21). 20% patients in group C whereas 54% in group S had complications (p= 0.009). There was a higher incidence of infections as well as respiratory distress in group S. On multiple logistic regression analysis peak environmental temperature was found to be the single independent risk factor for predicting perioperative morbidity. Conclusion: High ambient temperature adversely affects the outcome of surgery even in low risk young trauma patients belonging to American Society of Anaesthesia (ASA) physical status I and II categories. So we opine that it may be probably helpful to either postpone non-emergency surgery till fair adaptation is achieved in air conditioned environment of hospital or be cautious for complications to reduce the heat related perioperative morbidity in days of heat waves. [ABSTRACT FROM AUTHOR]

Cancer killed 5,56,400 people in the country in 2010 accounted for 8% total deaths. Chemotherapy is the treatment of choice for cancer patients but it is assisted with many side effects. The present study aimed to assess the effectiveness of progressive muscle relaxation technique on physical symptoms among cancer patients receiving chemotherapy. A modified graphing rating scale was used to assess nausea, common toxicity criteria for assessing vomiting, standardized 0-10 numeric pain rating scale were used to collect the data from a sample of 60 cancer patients receiving chemotherapy admitted in selected hospital of Amritsar, Punjab. 30 patients in experimental group and 30 patients in control group were selected using purposive sampling technique. In the present study Progressive Muscle Relaxation Technique is used as intervention. The results of the study showed that progressive muscle relaxation technique is highly effective in reducing the physical symptoms among cancer patients receiving chemotherapy in experimental group.The results of the study showed highly significant difference in pre-interventional and postinterventional physical symptoms of experimental and control group. Hence, it was concluded that progressive muscle relaxation technique is effective in reducing the physical symptoms due to chemotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: This systematic review and meta-analysis aimed to critically appraised data from comparable studies leading to quantitative assessment of any independent association between use of oral smokeless tobacco in any form, of betel quid without tobacco and of areca nut with incidence of oral cancer in South Asia and the Pacific. Methods: Studies (case control and/or cohort) were identified by searching Pub Med, CINAHL and Cochrane databases through June 2013 using the keywords oral cancer: chewing tobacco; smokeless tobacco; betel quid; betel quid without tobacco; areca nut; Asia, the Pacific and the reference lists of retrieved articles. A random effects model was used to compute adjusted summary ORRE for the main effect of these habits along with their corresponding 95% confidence intervals. To quantify the impact of between-study heterogeneity on adjusted main-effect summary ORRE, Higgins' H and I2 statistics along with their 95% uncertainty intervals were used. Funnel plots and Egger's test were used to evaluate publication bias. Results: Meta-analysis of fifteen case–control studies (4,553 cases; 8,632 controls) and four cohort studies (15,342) which met our inclusion criteria showed that chewing tobacco is significantly and independently associated with an increased risk of squamous-cell carcinoma of the oral cavity (adjusted main-effect summary for case- control studies ORRE = 7.46; 95% CI = 5.86–9.50, P<0.001), (adjusted main-effect summary for cohort studies RR = 5.48; 95% CI = 2.56–11.71, P<0.001). Furthermore, meta-analysis of fifteen case control studies (4,648 cases; 7,847 controls) has shown betel quid without tobacco to have an independent positive association with oral cancer, with OR = 2.82 (95% CI = 2.35–3.40, P<0.001). This is presumably due to the carcinogenicity of areca nut. There was no significant publication bias. Conclusion: There is convincing evidence that smokeless (aka chewing) tobacco, often used as a component of betel quid, and betel quid without tobacco, are both strong and independent risk factors for oral cancer in these populations. However, studies with better separation of the types of tobacco and the ways in which it is used, and studies with sufficient power to quantify dose-response relationships are still needed. [ABSTRACT FROM AUTHOR]

Ovarian Large Cell Neuroendocrine Carcinoma (LCNEC) is a recently described rare entity, which even more rarely occurs in a 'pure' form without any associated surface epithelial-stromal or germ cell component. Cervix metastasis of ovarian LCNEC has not been reported previously. We report here a case of ovarian LCNEC in a 35-year-old female who presented with abdominal pain and amenorrhea. Grossly the left ovary showed a solid cystic tumour measuring 6 cm in diameter. Histological examination showed a pure LCNEC without any associated component, confirmed by immunohistochemistry. Metastatic tumour deposits with numerous lymphovascular emboli were identified in the cervix. A comprehensive review of literature along with the various differential diagnosis is discussed. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to conduct a quantitative assessment of any independent association between past dental visits/check-ups and incidence of cancers of HN/upper aero-digestive tract (UADT) and oral cavity worldwide. Methods PubMed, CINAHL, and Cochrane databases were searched for all observational studies published until August 2017 that assessed an association of past dental visits/dental check-ups among the incident cases of HNC/UADT cancers. Three different meta-analyses were conducted: two based on the incident cancer reported in the studies (HNCs/cancers of UADT and oral cavity); another included all studies irrespective of the type of cancer reported with the frequency of past dental visits as subgroups. Results Sixty-two articles were reviewed in full, but only 38 were eligible for inclusion. Under the random effects model, odds of past never/irregular/ not frequent dental visits were greater in HNC cases and oral cancer cases as compared to the hospital based/ population-based controls [HNCs-unadjusted odds ratio (OR) 2.24; 95% confidence interval (CI) 1.89 to 2.65) and (oral cancers—OR 1.93; 95% CI 1.47 to 2.52]. There was no publication bias in our study. Conclusion This systematic review and meta-analysis indicates that individuals with never/irregular/not frequent dental visits are more likely to be incident cases of HNCs/UADT cancers. Key message Regular/frequent dental visits, at least annually, can aid in reducing the public health burden of head and neck cancers (HNCs) by facilitating earlier detection of the disease. [ABSTRACT FROM AUTHOR]

Abstract: The possibility of post-translational modifications of mannose binding lectin (MBL) leading to functional impairment of the MBL pathway and the presence of anti-MBL autoantibodies were reported earlier in rheumatoid arthritis (RA). MBL was observed to be S-nitrosylated (S-nitrosated) in vitro. HepG2 cells were stimulated with 10% synovial fluid from RA patients to produce increased levels of MBL and nitric oxide. Under these experimental conditions MBL was observed to be S-nitrosated using biotin switch assay. The plasma of RA patients was also found to contain higher levels of S-nitrosylated MBL (SNO-MBL) in comparison to the healthy controls. Functional activities of SNO-MBL were compared with normal MBL. Mannan binding and C4 deposition ability of MBL was found to decrease after S-nitrosylation. It was also observed that S-nitrosylation of MBL leads to a decrease in the bacterial phagocytosis and apoptotic cell binding as measured by fluorescence microscopy and FACS analysis. These results indicate that the carbohydrate binding ability of MBL was affected by S-nitrosylation (S-nitrosation). High levels of anti-MBL autoantibodies were detected against SNO-MBL in plasma of RA patients in comparison to normal MBL suggesting a role of SNO-MBL in generation of autoantibodies in RA patients. [Copyright &y& Elsevier]

Abstract: Objective: : Heat-mediated ELISA (HELISA) technique has been reported to shorten ELISA timings and has major clinical implications in diagnostic field [Bora U, Kannan K, Nahar P. Heat mediated enzyme linked immunosorbent assay. J Immunol Methods 2004; 293: 43–50]. Objective of this study is to find out whether anti-MBL autoantibody can be detected rapidly by HELISA technique. Design and methods: : Activated polystyrene microtiter plate was prepared by a photolinker in a photochemical reaction carried out over a period of 10 min. Lectin was covalently immobilized onto the activated plate at 50 °C in 45 min. Antigenicity of the immobilized lectin was checked by HELISA carried out at elevated temperature (50 °C). The result was further compared with that obtained by conventional ELISA method carried out on an untreated plate over an incubation period of 18 h. Results: : Autoantibody detection carried out by HELISA method (intra- and inter-assay CVs were <9.8%) in 2 h 45 min gives absorbance value comparable to that of conventional ELISA (intra- and inter-assay CVs were <12%) carried out in 18 h in RA patients and healthy controls (n =100). HELISA on a photoactivated surface showed 1.5-fold higher absorbance than those obtained on untreated surface (p =0.00019). The HELISA method is more sensitive (AUC=0.967, 95% CI=0.948–0.987) and can be used to detect autoantibody even at higher dilution than by conventional assay. Excellent correlation was observed when autoantibodies were detected by HELISA and conventional ELISA (R =0.9706). Conclusion: : The present method provides rapid and sensitive detection of autoantibody in rheumatoid arthritis patients. The method is precise and reliable similar to method currently used in diagnostics and could be potentially useful for other immunoassays. [Copyright &y& Elsevier]

Liposomes, modified with monoclonal antibodies, are suitable carriers for targeted delivery of chemotherapeutic drugs into brain tumors. Here, we investigate the therapeutic efficacy of monoclonal anticancer antibody 2C5-modified long-circulating liposomes (LCL) loaded with doxorubicin (2C5-DoxLCL) for the treatment of U-87 MG human brain tumors in an intracranial model in nude mice. In vitro, 2C5-DoxLCL is significantly more effective in killing the U-87 MG tumor cells than Doxil® (commercial doxorubicin-loaded PEGylated LCL) or DoxLCL modified with a non-specific IgG. 2C5-immunoliposomes also demonstrate a significantly higher accumulation in U-87 MG tumors compared to all controls in a subcutaneous model. The treatment of intracranial U-87 MG brain tumors in nude mice with 2C5-DoxLCL provides a significant therapeutic benefit over control formulations, substantially reducing the tumor size and almost doubling the survival time. Thus, monoclonal antibody 2C5-modified LCL can specifically target the anticancer drugs to brain tumors, leading to improved therapeutic treatment of brain tumor in an intracranial model, in vivo. [ABSTRACT FROM AUTHOR]

Abstract: The Ruta graveolens L. plant is used in traditional medicine to treat a large number of diseases. The methanol (50%) extract of the whole plant was observed to inhibit the expression of inducible nitric oxide synthase (iNOS) and the cycloxygenase-2 (COX-2) gene in lipopolysaccharide (LPS)-induced macrophage cells (J774A.1, [Raghav, S.K., Gupta, B., Agrawal, C., Goswami, K., Das, H.R., 2006b. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J. Ethnopharmacol. 104, 234–239]). The effect of whole plant extract on the expression of other pro-inflammatory genes such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ) and the activation of nuclear factor-kB (NF-κB) were investigated in LPS stimulated macrophage cells. An active compound was isolated from this methanol extract by further solvent fractionation and reverse phase high performance liquid chromatography (RP-HPLC). The purified compound was identified as 3-(1′-1′-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin having IUPAC nomenclature of 6-hydroxy-7-methoxy-3-(2-methyl but-3-en-2yl)-2H-chromen-2-one by ESI-MS, MALDI, FT-IR and NMR. Effect of this purified compound was assessed on iNOS, COX-2 and various pro-inflammatory cytokine genes and was observed to inhibit both the protein and mRNA expression of iNOS and IL-1β in LPS challenged macrophages. Electrophoretic mobility shift assay (EMSA) and Western blot analyses indicated that the plant extract and the isolated active compound blocked the LPS-induced activation of NF-κB through the prevention of inhibitor-kB (IkB) degradation. The purified compound also showed the anti-oxidant activity. The active compound at a dose of 40 mg/kg body weight was observed to inhibit the iNOS and IL-1β gene expression significantly in endotoxin-induced inflammatory model of BALB/c mice. The low level of nitric oxide production was also observed in the sera of compound treated mice. The normal behavioral condition in LPS challenged BALB/c mice was noticed when these were treated with active compound. [Copyright &y& Elsevier]

Abstract: Occurrence of autoantibodies in patients’ sera is the characteristic feature of autoimmune disorders. We assessed the presence of anti-mannose binding lectin (MBL) autoantibodies in the sera of 107 rheumatoid arthritis (RA) patients and 121 control subjects by enzyme immunoassay. Elevated levels of anti-MBL autoantibodies in the sera of RA patients (P <0.0001) was detected for the first time. The ratios of anti-MBL positive in RA patients and controls were respectively 60.7% and 1.65%. Experiments were then designed to understand the functional relevance of these autoantibodies. An inverse correlation of anti-MBL autoantibodies with serum MBL levels (P =0.001) and MBL complex activity (P =0.02) was observed without genetic association between MBL polymorphisms and anti-MBL autoantibody secretion. A significant increase (P =0.038) in the level of anti-MBL autoantibodies was observed in 23 synovial fluid samples in comparison to the serum samples. Moreover, the anti-MBL autoantibodies were found to be more often present in the sera of RA patients (60.75% sensitivity, 98.35% specificity and 0.913 area under the ROC curve) in comparison to the IgM and IgG isotypes of rheumatoid factors (RF). Anti-MBL autoantibodies were still positive in 25.23% RA patients when both the RF isotypes were negative. Also, in RA patients, at all stages of disease activity and joint deformity, anti-MBL autoantibodies were more often present than both the RF isotypes. Therefore, the significant presence of anti-MBL autoantibodies enunciates that anti-MBL autoantibodies might have a diagnostic value; however, more studies are needed to confirm the role of anti-MBL autoantibodies in the diagnosis of rheumatoid arthritis. [Copyright &y& Elsevier]

We examined the role of tumor necrosis factor (TNF-α) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-α receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-α and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-α induced signaling may not be explained only by these pathways. [ABSTRACT FROM AUTHOR]

We examined the role of tumor necrosis factor (TNF-α) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-α receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-α and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-α induced signaling may not be explained only by these pathways. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms in the mannose-binding lectin (MBL2) gene, as well as the serum MBL2 level, have been associated with various autoimmune diseases. We investigated whether such polymorphisms and/or the serum MBL2 level were associated with rheumatoid arthritis (RA) in an Indian population. The frequency of the B variant (codon 54) of the MBL2 gene was quite frequent in the healthy Indian population and was significantly ( P=6.35×10−6) lower in RA patients. We replicated this association ( P=1.78×10−5) in an independent cohort of control individuals. Promoter polymorphism at −550 nt showed a significant overrepresentation ( P=0.003) of the minor allele G in severe RA patients compared with the less severe group. Haplotype LYA frequency was significantly ( P=0.03) high in the less severe group, while the frequency of the HYA haplotype was significantly ( P=0.04) increased in the severe RA patients. No statistically significant difference in serum MBL2 was observed as a whole, but the individuals homozygous for the LYA haplotype had significantly lower ( P=0.017) serum MBL2 levels compared with individuals homozygous for the HYA haplotype. Therefore, the B variant of the MBL2 gene may be associated with protection from RA in our study population, and the promoter polymorphism (−550 nt) seems to have some role in disease progression. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the monoclonal antibody (mAb) 2C5 with nucleosome-restricted specificity for its ability to specifically recognize human brain tumor cells and to serve as a specific ligand for liposome targeting to brain tumor cells in vitro and in vivo . The affinity of mAb 2C5 towards brain tumor cells was tested by flow cytometry. The interaction of 2C5-immunoliposomes (ILS) with brain tumor cells in vitro was studied by fluorescence microscopy. For in vivo accumulation studies, 111 In-ILS were administered i.v. into mice bearing subcutaneously grown brain tumor. mAb 2C5 was found to be reactive against several tested brain tumor cell lines. mAb 2C5 and 2C5-ILS demonstrated enhanced cell-surface binding with CCF-STTG1,U-87 MG and LN-18 cells in vitro . 2C5-ILS displayed significantly better accumulation in the subcutaneously grown brain tumor than non-specific control IgG-ILS. mAb 2C5 specifically recognizes brain tumor cells and can serve as a ligand to target drug carriers such as liposomes to brain tumor cells in vivo . [ABSTRACT FROM AUTHOR]

Abstract: Cell-penetrating peptides (CPPs) have been used to overcome the lipophilic barrier of the cellular membranes and deliver large molecules and even small particles inside the cell for their biological actions. CPPs are being used to deliver inside cell a large variety of cargoes such as proteins, DNA, antibodies, contrast (imaging) agents, toxins, and nanoparticular drug carriers including liposomes. In this paper, we have reviewed the delivery of different molecules and particles mediated by TAT, Antp, VP22, and other CPPs as well as potential applications of these delivery systems in different areas of vaccine development, cancer immunotherapy, gene delivery, and cellular imaging. [Copyright &y& Elsevier]

Background: Regular/frequent dental visits, at least annually, can aid in reducing the public health burden of head and neck cancers (HNCs) by facilitating earlier detection of the disease. The aim of this study was to conduct a quantitative assessment of any independent association between past dental visits/check-ups and incidence of cancers of HN/upper aerodigestive tract (UADT) and oral cavity worldwide. Methods: PubMed, CINAHL, and Cochrane databases were searched for all observational studies published until August 2017 in any language that assessed an association of past dental visits/dental check-ups among the incident cases of HNC/UADT cancers. Screening and quality assessment of the articles was performed by two independent reviewers. Three different meta-analyses were conducted: two based on the incident cancer reported in the studies (HNCs/cancers of UADT and oral cavity); another included all studies irrespective of the type of cancer reported with the frequency of past dental visits as subgroups. Results: Searches retrieved 3164 titles: after removing duplicates, 1377 remained. Of these, 62 were reviewed in full, but only 38 were eligible for inclusion. Under the random effects model, odds of past never/irregular/not frequent dental visits were greater in HNC cases and oral cancer cases as compared to the hospital-based/population-based controls [HNCs-unadjusted odds ratio (OR) 2.24; 95% confidence interval (CI) 1.89 to 2.65) and (oral cancers—OR 1.93; 95% CI 1.47 to 2.52]. Similar results were observed for all cancers with frequency of past dental visits as subgroup analysis (OR 2.01; 95% CI 1.76 to 2.30). Meta-regression findings indicate that none of the subgroup influenced the effect estimates for incidence of cancers. There was no publication bias in our study. Conclusion: This systematic review and meta-analysis indicates that individuals with never/irregular/not frequent dental visits are more likely to be incident cases of HNCs/UADT cancers. [ABSTRACT FROM AUTHOR]

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. This is the first report depicting role of a Nuclear Receptor Co-repressor-1 (NCoR1) regulating autophagy induction and lysosomal biogenesis in myeloid cells by fine-tuning ATP homeostasis through AMPK-mTOR-TFEB signaling axis thereby controlling Mycobacterium tuberculosis pathogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Level of TNF-α increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population. Methods: In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity. Results: The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, χ2 =5.6, p ≤0.0179, OR=0.393, 95% CI=0.177–0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, χ2 =4.4, p ≤0.036, OR=1.55, 95% CI=1.027–2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, χ2 =6.22, p ≤0.013, OR=1.78, 95% CI=1.132–2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity. Conclusions: In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA. [Copyright &y& Elsevier]

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. Through this study we have focused on determining the role of ATP in etiology of RA and aberrant cellular functions. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

• Mitochondrial proteins are differentially expressed in RA PBMCs as compared to healthy controls. • Differentially expressed proteins are part of OXPHOS and mitochondrial dysfunction. • Mitochondrial membrane potential, superoxide levels and total cellular ATP are reduced in RA PBMCs. 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. [ABSTRACT FROM AUTHOR]

• L. rhamnosus reduces release of inflammatory molecules by CD8+T cells of RA patients. • Down regulation of Th1 cells by L. rhamnosus treated CD8+T cells of RA patients. • Viable L. rhamnosus negatively potentiated ERK activation. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Gaining interests and expediency of precision medicine for various diseases has led to the search for non invasive techniques like liquid biopsies involving study of circulating cell free DNA (cfDNA) for diagnostic as well as prognostic applications. Present study reports that cfDNA in plasma of patients with Rheumatoid Arthritis are fragmented, modified and hence remain undetected using qPCR, the commonly used analytical assay. They are immunogenic to peripheral blood cells and stimulate them to secrete TNF‐α, a pro‐inflammatory cytokine making it imperative to detect cfDNA in patients for an effective therapeutic intervention. Hereby a non‐invasive colorimetric assay for naked eye discernment of cfDNA using gold nanoparticles is proposed which is potent in detecting long and short cfDNA fragments from small amount of blood, is inexpensive, label free, easy to perform and allows visual detection. This can be further explored to assess its diagnostic and prognostics implications in various human disorders. Unmodified gold nanoparticles (AuNPs) have affinity towards cfDNA and show distinct color change upon interaction, but fail to do same with fragmented cfDNA. This mechanism has been further exploited to identify fragmentation status of cfDNA of RA patients which are found to be more fragmented and immunogenic in nature when compared with control samples. [ABSTRACT FROM AUTHOR]

Salmonella Enteritidis causes food-borne gastroenteritis by the two type three secretion systems (TTSS). TTSS-1 mediates invasion through intestinal lining, and TTSS-2 facilitates phagocytic survival. The pathogens' ability to infect effectively under TTSS-1-deficient background in host's phagocytes is poorly understood. Therefore, pathobiological understanding of TTSS-1-defective nontyphoidal Salmonellosis is highly important. We performed a comparative global proteomic analysis of the isogenic TTSS-1 mutant of Salmonella Enteritidis (M1511) and its wild-type isolate P125109. Our results showed 43 proteins were differentially expressed. Functional annotation further revealed that differentially expressed proteins belong to pathogenesis, tRNA and ncRNA metabolic processes. Three proteins, tryptophan subunit alpha chain, citrate lyase subunit alpha, and hypothetical protein 3202, were selected for in vitro analysis based on their functional annotations. Deletion mutants generated for the above proteins in the M1511 strain showed reduced intracellular survival inside macrophages in vitro. In sum, this study provides mass spectrometry-based evidence for seven hypothetical proteins, which will be subject of future investigations. Our study identifies proteins influencing virulence of Salmonella in the host. The study complements and further strengthens previously published research on proteins involved in enteropathogenesis of Salmonella and extends their role in noninvasive Salmonellosis. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • C-dots from genistein retain "structural memory" of the genistein precursor. • Genistein-C-dots exhibit antioxidant effect both in test-tube assays and in-vitro. • Genistein-C-dots treatment had pronounced anti-inflammatory effects in LPS stimulated RAW 264.7 macrophages. [ABSTRACT FROM AUTHOR]

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. AlthoughPIMkinases 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 upregulation 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 [ABSTRACT FROM AUTHOR]

Summary: 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. [Copyright &y& Elsevier]

Persistent viruses are kept in check by specific lymphocytes. The clonal T cell receptor (TCR) repertoire against Epstein-Barr virus (EBV), once established following primary infection, exhibits a robust stability over time. However, the determinants contributing to this long-term persistence are still poorly characterized. Taking advantage of an in vivo clinical setting where lymphocyte homeostasis was transiently perturbed, we studied EBV antigen-specific CD8 T cells before and after non-myeloablative lympho-depleting chemotherapy of melanoma patients. Despite more advanced T cell differentiation, patients T cells showed clonal composition comparable to healthy individuals, sharing a preference for TRBV20 and TRBV29 gene segment usage and several co-dominant public TCR clonotypes. Moreover, our data revealed the presence of relatively few dominant EBV antigen-specific T cell clonotypes, which mostly persisted following transient lympho-depletion (TLD) and lymphocyte recovery, likely related to absence of EBV reactivation and de novo T cell priming in these patients. Interestingly, persisting clonotypes frequently co-expressed memory/homing-associated genes (CD27, IL7R, EOMES, CD62L/SELL and CCR5) supporting the notion that they are particularly important for long-lasting CD8 T cell responses. Nevertheless, the clonal composition of EBV-specific CD8 T cells was preserved over time with the presence of the same dominant clonotypes after non-myeloablative chemotherapy. The observed clonotype persistence demonstrates high robustness of CD8 T cell homeostasis and reconstitution. [ABSTRACT FROM AUTHOR]