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The rhizomes of Curcuma caesia Roxb. (Family zingiberacea) are traditionally used to treat various ailments like piles, leprosy, asthma, cancer, wounds, impotency, fertility, toothache, vomiting leukoderma, tumours, bronchitis, etc. in Indian system of medicine. Rhizomes of C. caesia have been used as various ethnic herbal medicines by tribals. Several phytoconstituents have also been isolated and characterized. However, studies on correlation of phytoconstituents and medicinal properties are limited. The present study is an endeavor to do comprehensive review for the ethno-medicinal uses, pharmacology and phytochemistry of C. caesia. Pharmacological studies revealed the potent in vitro and in vivo bioactivities of various parts of C. caesia and other biological activities. Several phytoconstituents have been identified and isolated from C. caesia. Conclusions have been drawn from the literature reviewed and suggestions for future research are proposed. These findings may be utilized in the development of cost effective, safe and efficient novel drugs useful for treatment of cancer, piles, leprosy, asthma, wounds, impotency, fertility, toothache, vomiting, allergies and leukoderma.

Alkaloid and flavonoid contents of E. officinalis of leaf samples collected from five different geographical and climatic conditions have been compared in the present study. Comparison has also been made in terms of percent yield and number of constituents present in alkaloid and flavonoid samples as well as for antifungal potential against Fusarium oxysporum and Rhizoctonia solani. Alkaloid content is found to be maximum in samples collected from Banasthali, Rajasthan, an extremely hot and dry climatic zone. HPLC profiles indicate presence of maximum number of constituents in alkaloids separated from E. officinalis collected from Banasthali, Rajasthan. Flavonoid content has been found to be highest in samples collected from Palampur, Himachal Pradesh in extremely cold climatic zone followed by that of Banasthali, Rajasthan. Antifungal activity of alkaloids and flavonoids isolated from samples collected from Banasthali and Palampur has been found to be maximum for F. oxysporum and R. solani respectively. These studies reveal that geographical and climatic zones having extreme climatic conditions are more suitable to grow E. officinalis which is to be used as raw material for developing pesticidal formulations to control wilt and scurf diseases of potato.

Multiple cell types, molecules, and processes contribute to inhibition of anti-tumor effector responses, often frustrating effective immunotherapy. Among these, Foxp3+ CD4+ cells (Tregs) are well-recognized to play an immunosuppressive role in the tumor microenvironment. The first clinically successful checkpoint inhibitor, anti-CTLA-4 antibody, may deplete Tregs at least in part by antibody-dependent cellular cytotoxicity (ADCC), but this effect is unreliable in mice, including in a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC). In contrast, agonistic CD40 antibody, which serves as an effective therapy, is associated with notable Treg disappearance in the PDAC model. The mechanism of CD40-mediated Treg loss is poorly understood, as Tregs are CD40-negative. Here we have explored the mechanistic basis for the loss of Foxp3 T cells upon anti-CD40 treatment and find, using tissue-level multiplex immunostaining and orthogonal dissociated cell analyses, that Tregs are not depleted but converted into interferon-γ(IFN-γ) producing, Type I CD4+ T effector cells. This process depends on IL-12 and IFN-γsignaling evoked by action of the anti-CD40 antibody on dendritic cells (DCs), especially BATF3-dependent cDC1s. These findings provide insight into a previously unappreciated mechanism of CD40 agonism as a potent anti-tumor intervention that promotes the re-programming of Tregs into tumor-reactive CD4+ effector T cells, markedly augmenting the anti-tumor response.

Pancreatic adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the US partly because of its resistance to conventional chemotherapies. Immunotherapies that improve survival in many cancers, almost universally fail in PDA. The resistance to immune checkpoint blockade is at least partially explained by the lack of T cells in the tumor microenvironment (TME) in PDA. We have previously demonstrated that tumor cell-derived prostaglandin E2 (PGE2) is one of the tumor intrinsic factors that creates/supports immunosuppressive TME in PDA presumably through its paracrine effect on the stromal cells. In the current study, we investigate the role of autocrine PGE2 signaling through its cognate EP4 receptor in shaping the T cell low, myeloid cell rich PDA TME. The knockdown (EP4 KD) or knockout (EP4 KO) of the receptors on KrasG12D/p53R172H/YFP/PdxCre (KPCY) tumor cells was sufficient to suppress or abolish the growth of implanted tumors, respectively (control vs EP4 KD, p=0.01, and control vs EP4 KO, p Citation Format: Nune Markosyan, Charu Arora, Liz Quinones, Il-Kyu Kim, Nikhil Joshi, Noah Cheng, John Tobias, Ben Stanger, Robert Vonderheide. Tumor cell-intrinsic PGE2-EP4 signaling is a major immunosuppressive pathway in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3276.

Regulatory T cells (Tregs) are a pillar of the tumor microenvironment (TME), contributing to the restraint and dysfunction of adaptive immune responses against the tumor. Even small proportions of Tregs in the TME can subvert effector T cell responses, revealing the potent suppressive role of Tregs in both primary and acquired resistance to immune interventions. Therapeutically targeting Tregs to render the TME sensitive to immune destruction has been most successful using anti-CTLA-4, which is reported to bind intratumoral Tregs and mediate antibody dependent cellular cytotoxicity (ADCC). However, this therapy results in clinical responses in only a subset of patients and many tumor types are resistant to anti-CTLA-4, highlighting the need for improved options in targeting Tregs in the TME.As with most immune cells, Tregs exist on a spectrum, ranging from highly immunosuppressive to those with T helper (Th) effector functions, including production of interferon (IFN)-gamma. In studies of intestinal Treg subsets, conversion from a FoxP3+ suppressor conventional (cTreg) phenotype to a Th1-like ‘ExTreg’ phenotype has been reported. Given our recent findings that immunotherapy-induced CD4 T cells contribute to tumor rejection1,2, the impact of this switch from cTreg to ExTreg could be substantial in the context of the developing anti-tumor immune response. Here, we report for the first time the conversion of cTregs to ExTregs in the TME as a result of treatment with agonistic anti-CD40 monoclonal antibody. We employed anti-CD40 in the genetically engineered LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC) mouse model of pancreatic ductal adenocarcinoma (PDAC) as a means of priming an adaptive T cell response against established, highly immunosuppressive tumors3. We have previously reported the positive impact of anti-CD40 combined with dual immune checkpoint blockade (anti-PD-1 and anti-CTLA-4; ICB) on the generation of protective CD4 and CD8 T cell responses in the context of PDAC, concurrent with a decline of Tregs in the PDAC TME1. Leveraging a PDAC tumor clone with a relatively high T cell infiltrate to assess the impact of ‘successful’ immunotherapy on the TME4, we observed significant alterations in the Treg compartment after combination anti-CD40 and ICB administration, including a global reduction in Tregs and a pattern of Treg localization at the tumor edge. Interrogation of the mechanisms underlying Treg loss after therapy revealed the effect was entirely dependent on CD40 stimulation, as anti-CD40 alone mediated this effect and mice lackingCD40 expression were resistant to Treg reduction. Given that Tregs do not express CD40, excluding the role of ADCC in mediating Treg loss in the TME, we hypothesized that CD40-expressing antigen presenting cells may mediate intratumoral Treg reduction. We found that dendritic cells (DCs) and the IL-12/IFN-gamma cytokine signaling pathway regulated Treg loss, but that Tregs were not dying at increased rates, as FoxP3+ cells did not express increased levels of cleaved caspase 3 after treatment with anti-CD40. Using FoxP3eGFP-Cre-ERT2 xGt(ROSA)26Sortm(CAGtdTomato)/Hze (R26tdTomato) mice to conduct lineage tracing experiments, we determined that Tregs in the PDAC TME downregulated FoxP3 expression, converting from a cTreg to ExTreg phenotype. Concurrently, all Treg subsets upregulated expression of the Th1transcription factor Tbet, and ExTregs increased production of IFN-gamma. This effect was completely lost in mice treated with antibodies blocking either IL-12p40 or IFN-gamma, highlighting the role of this cytokine axis in regulating ExTreg generation and acquisition of Th1effector functions. Furthermore, nuclear translocation of the nuclear factor of activated T cells (NFAT1), a reliable marker of extremely recent cognate antigen stimulation of T cells ( Citation Format: Vivien Maltez, Charu Arora, Rina Sor, Ronald N. Germain, Robert H. Vonderheide, Katelyn T. Byrne. Agonistic anti-CD40 converts regulatory T cells in to Type 1 effector cells within the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG04.

In the proposed model, a prey-predator system with migration in both species along with the disease in prey population is considered. To study the dynamics among healthy predator, susceptible prey and infected prey, Holling type II functional response is incorporated. The model has been examined using local stability analysis around the existing equilibrium points and by considering migration in susceptible prey as the control parameter, bifurcation conditions are discussed in brief. Basic reproduction number is determined which affirms the disease to be endemic or not and global stability analysis has been implemented using geometric approach. At the end, numerical simulation to support theoretical results is exhibited.

Pulsed electron paramagnetic resonance (EPR) based distance measurements using the recently developed Cu2+-DPA label present a promising strategy for measuring DNA backbone distance constraints. Herein we develop force field parameters for Cu2+-DPA in order to understand the features of this label at an atomic level. We perform molecular dynamics (MD) simulations using the force field parameters of Cu2+-DPA on four different DNA duplexes. The distance between the Cu2+ centers, extracted from the 2 μs MD trajectories, agrees well with the experimental distance for all the duplexes. Further analyses of the trajectory provide insight into the orientation of the Cu2+-DPA inside the duplex that leads to such agreement with experiments. The MD results also illustrate the ability of the Cu2+-DPA to report on the DNA backbone distance constraints. Furthermore, measurement of fluctuations of individual residues showed that the flexibility of Cu2+-DPA in a DNA depends on the position of the label in the duplex, and a 2 μs MD simulation is not sufficient to fully capture the experimental distribution in some cases. Finally, the MD trajectories were utilized to understand the key aspects of the double electron electron resonance (DEER) results. The lack of orientational selectivity effects of the Cu2+-DPA at Q-band frequency is rationalized in terms of fluctuations in the Cu2+ coordination environment and rotameric fluctuations of the label linker. Overall, a combination of EPR and MD simulations based on the Cu2+-DPA labelling strategy can contribute towards understanding changes in DNA backbone conformations during protein–DNA interactions.

This analysis on key nutrition indicators from successive rounds of the NFHS (4 and 5) is based on all-India and State/UT level factsheet released by Ministry of Health and Family Welfare (MoHFW). The analysis includes: 1. National level trends from NFHS-3 (2005-06), NFHS-4 (2015-16) and NFHS-5 (2019-21) data for 44 indicators including outcomes, service delivery and key determinants of nutrition. 2. State level trends of same indicators- number of states showing improvement / worsening (± 0.1 percent point change), /no change for these indicators, spatial maps based on change in prevalence for these indicators; and charting State performance with respect to achieving Sustainable Development Goals (SDG 2030) targets. This presentation will be useful for policy makers, State administrators, public health experts, research scholars and research institutes in the area of maternal and child health & Nutrition.

Lifestyle intervention is the mainstay therapy for Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to assess the efficacy of an intensive (9 contact points in 6 months) weight-loss intervention among patients with obesity (BMI 25-39.9 kg/mA total of 140 patients (18-60 years) with obesity and NAFLD were randomized into intervention (n = 70) and control (n = 70) groups, at a tertiary-care hospital. Weight, anthropometric parameters, Controlled Attenuation Parameter (CAP), Liver Stiffness Measurement (LSM), liver enzymes, grade of fatty liver and HOMA-IR were measured at baseline (TAt TThe intensive weight-loss intervention was not effective in improving the treatment outcomes among patients with obesity and NAFLD. However, given the potential of our intervention, we recommend larger trials with more intensive weight-loss interventions.

Randomized controlled trials (RCTs) provide the best quality evidence to steer patient care in the field of clinical nutrition. However, designing and conducting an RCT, analyzing data, interpreting and reporting its findings is rather complex for young researchers working in the field of clinical nutrition. This review article attempts to educate early researchers by offering a simple step by step guide on planning the key aspects (randomization, allocation concealment, blinding, outcome measures) of a trial, and highlighting the practical considerations (ethical clearance, trial registry, patient recruitment, trial monitoring) to be kept in mind while conducting a trial contextualised to clinical nutrition settings.

In today’s era of globalization, clinicians have to deal with a diverse patient population, coming from a varied range of cultural, linguistic, and socio-economic backgrounds. Modern-day medicine e...

The present investigation assesses the applicability of Fe-BDC metal organic framework for the removal of the toxic dye methylene blue from industrial waste. The adsorption characteristics and dye removal efficiency of Fe-BDC MOF has been determined by investigating factors such as effect of contact time, concentration of the dye, amount of adsorbents, and temperature. Upto 94.74% dye removal was attained by increasing the dose of adsorbent and temperature. Maximum 94.74% dye removal was achieved after 24 h, on adding 25 mg of Fe-BDC MOF to dye solution of MB having concentration 5 mg/L. Langmuir, Freundlich and Tempkin, isotherm models have been used to evaluate the ongoing adsorption. Freundlich adsorption isotherm was found to be best fitted for the adsorption process. On the basis of pseudo-first-order, pseudo-second-order and intra particle diffusion kinetic equations, different kinetic parameters have been obtained. Pseudo second order kinetic model with rate constant (k2) 4.9 × 10−2 g/mg·min, is found to be best fitted for adsorption of methylene blue on Fe-BDC MOF indicating that removal of dye takes place dominantly through chemisorption process.

Aim: The objective of this study was to develop and validate a knowledge, attitude, and practice (KAP) questionnaire about obesity among obese individuals. Materials and Methods: The questionnaire was developed following a standardized protocol that consisted of literature review, focused group discussions, and expert opinion. A cross-sectional survey on 100 obese individuals was carried out to validate the tool. Exploratory factor analysis was performed, using principal component with varimax rotation, to establish the construct validity of the questionnaire. Internal consistency of the questionnaire was tested using Cronbach's α coefficient. Results: KAP questionnaire with 42 items categorized under three domains knowledge, attitude, and practices was developed. The KAP sections have 14, 15, and 13 items, respectively. Independent Cronbach's α for KAP domains were 0.75, 0.75, and 0.63, respectively, indicating good internal consistency. Conclusion: The developed questionnaire will be helpful in achieving better understanding of the patients' KAP about obesity. It has satisfactory validity and good internal consistency.