Utilizing Artificial Intelligence Among Patients With Diabetes: A Systematic Review and Meta-Analysis.

Diabetes mellitus, a condition characterized by dysregulation of blood glucose levels, poses significant health challenges globally. This meta-analysis and systematic review aimed to evaluate the effectiveness of artificial intelligence (AI) in managing diabetes, underpinned by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review scrutinized articles published between January 2019 and February 2024, sourced from six electronic databases: Web of Science, Google Scholar, PubMed, Cochrane Library, EMBASE, and MEDLINE, using keywords such as "Artificial intelligence use in medicine, Diabetes management, Health technology, Machine learning, Diabetic patients, AI applications, and Health informatics." The analysis revealed a notable variance in the prevalence of diabetes symptoms between patients managed with AI models and those receiving standard treatments or other machine learning models, with a risk ratio (RR) of 0.98 (95% CI: 0.88-1.08, I2 = 0%). Sub-group analyses, focusing on symptom detection and management, consistently showed outcomes favoring AI interventions, with RRs of 0.97 (95% CI: 0.87-1.08, I2 = 0%) for symptom detection and 0.97 (95% CI: 0.56-1.57, I2 = 0%) for management, respectively. The findings underscore the potential of AI in enhancing diabetes care, particularly in early disease detection and personalized lifestyle recommendations, addressing the significant health risks associated with diabetes, including increased morbidity and mortality. This study highlights the promising role of AI in revolutionizing diabetes management, advocating for its expanded use in healthcare settings to improve patient outcomes and optimize treatment efficacy.

The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study.

Introduction: Murine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process. Interventional role of NLGP in initiation-promotion protocol established during 4NQO mediated tongue carcinogenesis in relation to systemic immune alteration and epithelial-mesenchymal transition (EMT) is investigated. Methods: 4NQO was painted on tongue of Swiss mice every third day at a dose of 25µl of 5mg/ml stock solution. After five consecutive treatment with 4NQO (starting Day7), one group of mice was treated with NLGP (s.c., 25µg/mice/week), keeping a group as PBS control. Mice were sacrificed in different time-intervals to harvest tongues and studied using histology, immunohistochemistry, flow-cytometry and RT-PCR on different immune cells and EMT markers (e-cadherin, vimentin) to elucidate their phenotypic and secretory status. Results: Local administration of 4NQO for consecutive 300 days promotes significant alteration in tongue mucosa including erosion in papillae and migration of malignant epithelial cells to the underlying connective tissue stroma with the formation of cell nests (exophytic-hyperkeratosis with mild dysplasia). Therapeutic NLGP treatment delayed pre-neoplastic changes promoting normalization of mucosa by maintaining normal structure. Flow-cytometric evidences suggest that NLGP treatment upregulated CD8+, IFNγ+, granzyme B+, CD11c+ cells in comparison to 4NQO treated mice with a decrease in Ki67+ and CD4+FoxP3+ cells in NLGP treated cohort. RT-PCR demonstrated a marked reduction of MMP9, IL-6, IL-2, CD31 and an upregulation in CCR5 in tongues from 4NQO+NLGP treated mice in comparison to 4NQO treated group. Moreover, 4NQO mediated changes were associated with reduction of e-cadherin and simultaneous up-regulation of vimentin expression in epithelium that was partially reversed by NLGP. Discussion: Efficacy of NLGP was tested first time in sequential carcinogenesis model and proved effective in delaying the initial progression. NLGP normalizes type 1 immunity including activation of the CD8+T effector functions, reduction of regulatory T cell functions, along with changes in EMT to make the host systemically alert to combat the carcinogenic threat.

Investigating the Prevalence of Menopausal Symptoms and Medico-Social Dimensions of Menopause in Rural Puducherry, India: A Cross-Sectional Analytical Study.

Introduction Globally, the health of women has been of great concern for healthcare providers for the past many years. However, the concern is limited to maternal and adolescent health and the life course approach is lagging. Thus, a need was felt to study the changes after menopause and its influential factors by determining the prevalence of menopausal symptoms and medico-socio-cultural dimensions of menopause among perimenopausal and early postmenopausal women. Methodology A cross-sectional analytical study was conducted from February 2014 to April 2015 in a rural area of Puducherry among 148 women in perimenopausal and early postmenopausal stages by complete enumeration using a pre-tested semi-structured questionnaire. Prevalence was expressed as frequency with percentage and the chi-square test was used to find the association among the study variables. Results The prevalence of menopausal symptoms was in 143 (96.6%) women. Backache (62.3%) was found to have a higher prevalence. Physical symptoms (93.2%) were most prevalent. Of the women, 95% were affected by mild symptoms. Regarding medical and social dimensions of menopausal symptoms, socioeconomic status to vasomotor, age of menarche to physical, marital status, and abortion status to sexual symptoms were significant. A positive correlation was seen among the four menopausal symptom domains, except for vasomotor to sexual symptoms. Conclusion Increased prevalence of menopausal symptoms is seen among menopausal women who are unaware of seeking medical advice. Additional emphasis should be placed on implementing programmes that will critically help to sensitize and intensify the awareness of menopause among women in India.

Internal Hernia Through a Congenital Defect in Broad Ligament: A Rare and Elusive Cause of Intestinal Obstruction.

Internal hernias through a defect in the broad ligament is an uncommon cause of intestinal obstruction and most often the finding is intra-operative. What makes it rare is when the hernia occurs through a congenital defect in the broad ligament. We present the case of a 48-year-old female patient operated on an emergency basis for intestinal obstruction and intra-operatively the cause was identified to be a herniated ileal loop through a defect in the broad ligament. There was no history of any prior abdominal surgery or any interventions and all of her children were born by normal vaginal delivery, making it a case of congenital broad ligament defect. The postoperative period was uneventful and she was discharged in good health.

Partial oxidation of methane to methanol on boron nitride at near critical acetonitrile.

Direct catalytic conversion of methane to methanol with O2 has been a fundamental challenge in unlocking abundant natural gas supplies. Metal-free methane conversion with 17% methanol yield based on the limiting reagent O2 at 275 °C was achieved with near supercritical acetonitrile in the presence of boron nitride. Reaction temperature, catalyst loading, dwell time, methane-oxygen molar ratio, and solvent-oxygen molar ratios were identified as critical factors controlling methane activation and the methanol yield. Extension of the study to ethane (C2) showed moderate yields of methanol (3.6%) and ethanol (4.5%).

Strategies to overcome vaccine hesitancy: a systematic review.

BACKGROUND: Vaccination, albeit a necessity in the prevention of infectious diseases, requires appropriate strategies for addressing vaccine hesitancy at an individual and community level. However, there remains a glaring scarcity of available literature in that regard. Therefore, this review aims to scrutinize globally tested interventions to increase the vaccination uptake by addressing vaccine hesitancy at various stages of these interventions across the globe and help policy makers in implementing appropriate strategies to address the issue. METHODS: A systematic review of descriptive and analytic studies was conducted using specific key word searches to identify literature containing information about interventions directed at vaccine hesitancy. The search was done using PubMed, Global Health, and Science Direct databases. Data extraction was based on study characteristics such as author details; study design; and type, duration, and outcome of an intervention. RESULTS: A total of 105 studies were identified of which 33 studies were included in the final review. Community-based interventions, monetary incentives, and technology-based health literacy demonstrated significant improvement in the utilization of immunization services. On the other hand, media-based intervention studies did not bring about a desired change in overcoming vaccine hesitancy. CONCLUSION: This study indicates that the strategies should be based on the need and reasons for vaccine hesitancy for the targeted population. A multidimensional approach involving community members, families, and individuals is required to address this challenging issue.

Return on investment of the electronic vaccine intelligence network in India.

The electronic vaccine intelligence network (eVIN) was introduced by India's Ministry of Health and Family Welfare in 12 states and was implemented by the United Nations Development Programme through the Gavi health system strengthening support during 2014-17 to replace the traditional paper-based cold-chain management system with an electronic vaccine logistics management system. An economic assessment was conducted as part of the overall assessment of eVIN. The objective of the economic assessment was to conduct a return on investment analysis of eVIN implementation. Return on investment was defined as the ratio of total benefits (savings) from eVIN to total investment in eVIN. All costs were calculated in 2020 prices and reported in Indian rupees (1 US dollar = INR 74.132). A one-rupee investment in eVIN led to a return of INR 0.52 for traditional vaccines. The highest cost savings from eVIN was from better vaccine stock management. When same percentage of savings from the new vaccines were incorporated into the analysis, one-rupee investment in eVIN led to a return of INR 1.41. In the future, when only recurrent costs will exist, the return from eVIN will be even higher: a one-rupee investment in eVIN will yield a return of INR 2.93. The assessment of eVIN showed promising results in streamlining the vaccine flow network and ensuring equity in vaccine stock management along with good return on investment; hence, there was a rapid expansion of eVIN in all 731 districts across 36 states and union territories in the country.

Role of catalytic nitrile decomposition in tricopper complex mediated direct partial oxidation of methane to methanol.

Synthetic homogeneous system known to date performing methane to methanol conversion using O2 as terminal oxidant is unique and based on copper complex with piperazine-based ligand (Cu3L in Fig. 1) in a medium of acetonitrile. Prior work have shown that in order to achieve catalytic turnover, hydrogen peroxide is needed to regenerate the active site. We show in this paper that reaction solvent based on organic nitrile decompose concurrently with methane activation and that in the absence of either acetonitrile, Cu complex or hydrogen peroxide, the catalytic turnover does not happen. We show in this manuscript that the direct methane oxidation to methanol might have been mediated by catalytic Radziszewski oxidation between acetonitrile and H2O2. Additionally we have discovered that in the absence of methane, peroxide mediated acetonitrile decomposition also makes methanol via a background reaction which was hitherto unknown.

RGS5-TGFß-Smad2/3 axis switches pro- to anti-apoptotic signaling in tumor-residing pericytes, assisting tumor growth.

Regulator-of-G-protein-signaling-5 (RGS5), a pro-apoptotic/anti-proliferative protein, is a signature molecule of tumor-associated pericytes, highly expressed in several cancers, and is associated with tumor growth and poor prognosis. Surprisingly, despite the negative influence of intrinsic RGS5 expression on pericyte survival, RGS5highpericytes accumulate in progressively growing tumors. However, responsible factor(s) and altered-pathway(s) are yet to report. RGS5 binds with Gαi/q and promotes pericyte apoptosis in vitro, subsequently blocking GPCR-downstream PI3K-AKT signaling leading to Bcl2 downregulation and promotion of PUMA-p53-Bax-mediated mitochondrial damage. However, within tumor microenvironment (TME), TGFß appeared to limit the cytocidal action of RGS5 in tumor-residing RGS5highpericytes. We observed that in the presence of high RGS5 concentrations, TGFß-TGFßR interactions in the tumor-associated pericytes lead to the promotion of pSmad2-RGS5 binding and nuclear trafficking of RGS5, which coordinately suppressed RGS5-Gαi/q and pSmad2/3-Smad4 pairing. The RGS5-TGFß-pSmad2 axis thus mitigates both RGS5- and TGFß-dependent cellular apoptosis, resulting in sustained pericyte survival/expansion within the TME by rescuing PI3K-AKT signaling and preventing mitochondrial damage and caspase activation. This study reports a novel mechanism by which TGFß fortifies and promotes survival of tumor pericytes by switching pro- to anti-apoptotic RGS5 signaling in TME. Understanding this altered RGS5 signaling might prove beneficial in designing future cancer therapy.

Awareness of diabetes risk factors among Bisha Residents Southwestern Saudi Arabia.

Introduction: In the past few decades, the prevalence of type 2 diabetes has increased dramatically in many countries. While primary preventive measures can reduce the prevalence of diabetes, knowledge of the risk factors of diabetes mellitus has many benefits for patients with diabetes. The study aimed to assess diabetes mellitus risk factors (DM-RFs) awareness among adults residing in Bisha, Southwestern Saudi Arabia. Awareness of the risk factors of diabetes mellitus was reported to be highest for obesity, sweet intake, and family history of diabetes. Methods: The study participants were 404 adults (225 males and 179 females) with an age range of 18-65 (mean age: 40.83+/-9.3). People with diabetes and those without diabetes were involved in the study. The study was conducted in Bisha city, southwestern Saudi Arabia, using an online random sampling technique and a structured and validated questionnaire, and analysis was by SPSS V 24. Results: This study showed that 168 (41.6%) participants had diabetes and 236 (58.4%) were non-diabetics; 64.9% of the respondents were aware of the DM-RFs. Among the people with diabetes, 128 (76.2%) agreed that obesity is a DM-RF, while 210 (89%) of the non-diabetics were aware that obesity was a DM-RF. Further, 77.7% of the respondents agreed that the risk factors were avoidable, with 50.7% willing to know more about DM-RFs. Conclusion: The study found a high level of awareness of DM-RFs among diabetes and non-diabetics in Bisha, southwestern Saudi Arabia.

Programmatic assessment of electronic Vaccine Intelligence Network (eVIN).

eVIN is a technology system that digitizes vaccine stocks through a smartphone application and builds the capacity of program managers and cold chain handlers to integrate technology in their regular work. To effectively manage the vaccine logistics, in 2015, this technology was rolled-out in 12 states of India. This study assessed the programmatic usefulness of eVIN implementation in the areas of vaccine utilization, vaccine stock and distribution management and documentation across selected cold chain points. A pre-post study design was used, where cold chain points (CCPs) were selected using two-stage sampling technique in eVIN states. Pre-post comparative analysis was carried out on the identified indicators using both primary and secondary data sources. The vaccine utilization data reflects that the utilization had reduced from 305.3 million doses in pre-eVIN period to 215.0 million doses in post-eVIN period across 12 eVIN states, resulting into savings of approximately 90 million doses of vaccines. Number of facilities having stock-out of any vaccine showed a significant reduction by 30.4% in post-eVIN period (p<0.001). There was a 4.0% drop in facilities reporting minimum stock of any vaccine after implementation of eVIN. Facilities with maximum stock of any vaccine had increased from 37.4% in pre-eVIN to 39.2% in post-eVIN. During the pre-eVIN period, only 38.6% facilities updated vaccine stock on a daily basis, while in post-eVIN period, 53.5% facilities updated vaccine stock on daily basis. The completeness of records in the vaccine stock registers, indent form and temperature logbook have been substantially improved in the post-eVIN period (p<0.001). eVIN had helped in streamlining the vaccine flow network and ensured equity through better vaccine management practices. It is a powerful contribution to strengthen the vaccine supply chain and management. Upscaling eVIN in the remaining states of India will be crucial in improving the efficacy of vaccines and cold chain management.

Retroperitoneal Bronchogenic Cyst: A Rare Case Study.

Bronchogenic cyst usually presents along the tracheobronchial tree. Rarely, it is found inside peritoneal cavity. Here is a case of 30-year-old man who presented with concerns of abdominal pain. On evaluation, contrast-enhanced CT scan showed hypodense cystic lesion in epigastric region related to right crus of diaphragm. The patient underwent laparoscopic marsupialization/deroofing of cyst. Histopathological examination of resected specimen showed respiratory epithelium. Postoperative period was uneventful.

Neem leaf glycoprotein reverses tumor-induced and age-associated thymic involution to maintain peripheral CD8+ T cell pool.

Aim: As tumor causes atrophy in the thymus to target effector-T cells, this study is aimed to decipher the efficacy of neem leaf glycoprotein (NLGP) in tumor- and age-associated thymic atrophy. Materials & methods: Different thymus parameters were studied using flow cytometry, reverse transcriptase PCR and immunocyto-/histochemistry in murine melanoma and sarcoma models. Results: Longitudinal NLGP therapy in tumor hosts show tumor-reduction along with significant normalization of thymic alterations. NLGP downregulates intrathymic IL-10, which eventually promotes Notch1 to rescue blockade in CD25+CD44+c-Kit+DN2 to CD25+CD44-c-Kit-DN3 transition in T cell maturation and suppress Ikaros/IRF8/Pu.1 to prevent DN2-T to DC differentiation in tumor hosts. The CD5intTCRαßhigh DP3 population was also increased to endorse CD8+ T cell generation. Conclusion: NLGP rescues tumor-induced altered thymic events to generate more effector T cells to restrain tumor.

Tumor Arrests DN2 to DN3 Pro T Cell Transition and Promotes Its Conversion to Thymic Dendritic Cells by Reciprocally Regulating Notch1 and Ikaros Signaling.

Tumor progression in the host leads to severe impairment of intrathymic T-cell differentiation/maturation, leading to the paralysis of cellular anti-tumor immunity. Such suppression manifests the erosion of CD4+CD8+ double-positive (DP) immature thymocytes and a gradual increase in CD4-CD8- double negative (DN) early T-cell progenitors. The impact of such changes on the T-cell progenitor pool in the context of cancer remains poorly investigated. Here, we show that tumor progression blocks the transition of Lin-Thy1.2+CD25+CD44+c-KitlowDN2b to Lin-Thy1.2+CD25+CD44-c-Kit-DN3 in T-cell maturation, instead leading to DN2-T-cell differentiation into dendritic cells (DC). We observed that thymic IL-10 expression is upregulated, particularly at cortico-medullary junctions (CMJ), under conditions of progressive disease, resulting in the termination of IL-10Rhigh DN2-T-cell maturation due to dysregulated expression of Notch1 and its target, CCR7 (thus restricting these cells to the CMJ). Intrathymic differentiation of T-cell precursors in IL-10-/- mice and in vitro fetal thymic organ cultures revealed that IL-10 promotes the interaction between thymic stromal cells and Notch1low DN2-T cells, thus facilitating these DN2-T cells to differentiate toward CD45+CD11c+MHC-II+ thymic DCs as a consequence of activating the Ikaros/IRF8 signaling axis. We conclude that a novel function of thymically-expressed IL-10 in the tumor-bearing host diverts T-cell differentiation toward a DC pathway, thus limiting the protective adaptive immune repertoire.

NLGP Attenuates Murine Melanoma and Carcinoma Metastasis by Modulating Cytotoxic CD8+ T Cells.

Neem leaf glycoprotein (NLGP), a natural immunomodulator, attenuates murine carcinoma and melanoma metastasis, independent of primary tumor growth and alterations in basic cellular properties (cell proliferation, cytokine secretion, etc.). Colonization event of invasion-metastasis cascade was primarily inhibited by NLGP, with no effect on metastasis-related invasion, migration, and extravasation. High infiltration of interferon γ (IFN-γ)-secreting cytotoxic CD8+ T cells [CD44+, CD69+, GranB+, IFN-γ+, and interleukin 2+] was documented in the metastatic site of NLGP-treated mice. Systemic CD8+ T cell depletion abolished NLGP-mediated metastasis inhibition and reappeared upon adoptive transfer of NLGP-activated CD8+ T cells. Interferon γ-secreting from CD8+ T cells inhibit the expression of angiogenesis regulatory vascular endothelial growth factor and transforming growth factor ß and have an impact on the prevention of colonization. Neem leaf glycoprotein modulates dendritic cells (DCs) for proper antigen presentation by its DC surface binding and upregulation of MHC-I/II, CD86, and CCR7. Neem leaf glycoprotein-treated DCs specifically imprint CXCR3 and CCR4 homing receptors on activated CD8+ T cells, which helps to infiltrate into metastatic sites to restrain colonization. Such NLGP's effect on DCs is translation dependent and transcription independent. Studies using ovalbumin, OVA257-264, and crude B16F10 antigen indicate MHC-I upregulation depends on the quantity of proteasome degradable peptide and only stimulates CD8+ T cells in the presence of antigen. Overall data suggest NLGP inhibits metastasis, in conjunction with tumor growth restriction, and thus might appear as a promising next-generation cancer immunotherapeutic.

Neem Leaf Glycoprotein Restrains VEGF Production by Direct Modulation of HIF1α-Linked Upstream and Downstream Cascades.

Neem Leaf Glycoprotein (NLGP) is a natural immunomodulator, have shown sustained tumor growth restriction as well as angiogenic normalization chiefly by activating CD8+ T cells. Here, we have investigated the direct role of NLGP as a regulator of tumor microenvironmental hypoxia and associated vascular endothelial growth factor (VEGF) production. We observed a significant reduction in VEGF level in both in vivo murine tumor and in vitro cancer cells (B16Mel, LLC) and macrophages after NLGP treatment. Interestingly, NLGP mediated VEGF downregulation in tumor cells or macrophages within hypoxic chamber was found at an early 4 h and again at late 24 h in mRNA level. Our data suggested that NLGP prevented hypoxia-induced strong binding of HIF1α with its co-factors, CBP/p300 and Sp3, but not with Sp1, which eventually limit the binding of HIF1α-transcriptional complex to hypoxia responsive element of VEGF promoter and results in restricted early VEGF transcription. On the otherhand, suppressed phosphorylation of Stat3 by NLGP results reduction of HIF1α at 24 h of hypoxia that further support sustained VEGF down-regulation. However, NLGP fails to regulate VHL activity as observed by both in vivo and in vitro studies. Therefore, this study for the first time reveals a mechanistic insight of NLGP mediated inhibition of angiogenesis by suppressing VEGF, which might help in vascular normalization to influence better drug delivery.

PKCζ mediated anti-proliferative effect of C2 ceramide on neutralization of the tumor microenvironment and melanoma regression.

Immunotherapy, which has advantages over chemotherapy due to lesser toxicity and higher specificity, is on the rise to treat cancer. Recently, pro-apoptotic glycolipid, ceramide has emerged as a key regulator in cancer immunotherapy. The present study elucidated the potential anti-melanoma efficacy of cell-permeable, exogenous C2 ceramide on cell death and amelioration of tumor microenvironment (TME). We, for the first time, demonstrated that C2 ceramide triggered apoptosis of melanoma cells by augmenting PKCζ along with pro-inflammatory cytokines and signaling factors. C2 ceramide showed a PKCζ-mediated tumor-suppressive role in melanoma without exhibiting hepatotoxicity and nephrotoxicity. Moreover, PKCζ was revealed as one of the key regulators of Akt and ceramide during C2 ceramide-mediated apoptosis. C2 ceramide was effective in repolarization of M2 macrophage phenotype and reduction of angiogenic factors such as VEGF, VEGFR1, VEGFR2, HIF1α. Interestingly, PKCζ knockdown attenuated C2 ceramide-mediated inhibition of melanoma progression. Restoration of the Th1 type TME by C2 ceramide enhanced cytotoxic T cell-mediated killing of melanoma cells. Altogether, the study unraveled that C2 ceramide-induced PKCζ was associated with favorable immune cell functioning in TME leading to melanoma regression. Thus, our findings explored a novel mechanistic insight into C2 ceramide as a promising immunotherapeutic agent in melanoma treatment.

NMR of petrochemical-type chemical reactions.

A simple technique is presented for NMR of chemically reacting systems at conditions of high temperature and pressure. The method can follow reactions that are typical of refinery operations - hydrogenation, transfer dehydrogenation, methanol synthesis, and isomerization. All of the reacting materials are flame-sealed into a glass capillary. Gaseous agents such as O2 and CO are loaded into the capillary by condensation at liquid N2 temperature. H2 is provided by loading LiAlH4. The capillary holds the high pressure, up to 7 MPa, so the NMR probe can be a simple design with hot air flowing over the sample tube, up to 350 °C. Example reaction results are presented, including hydrogenation of benzene, hydrogenation/dehydrogenation of cyclohexene to benzene and cyclohexane (a disproportionation), and synthesis of methane, methanol and dimethyl ether from CO and H2. In this work we present a simple, inexpensive method with rapid temperature response for tracking chemical reactions in real-time at high temperature and high pressure.

NLGP counterbalances the immunosuppressive effect of tumor-associated mesenchymal stem cells to restore effector T cell functions.

BACKGROUND: A dynamic interaction between tumor cells and its surrounding stroma promotes the initiation, progression, metastasis, and chemoresistance of solid tumors. Emerging evidences suggest that targeting the stromal events could improve the efficacies of current therapeutics. Within tumor microenvironment (TME), stromal progenitor cells, i.e., MSCs, interact and eventually modulate the biology and functions of cancer and immune cells. Our recent finding disclosed a novel mechanism stating that tumor-associated MSCs inhibit the T cell proliferation and effector functions by blocking cysteine transport to T cells by dendritic cells (DCs), which makes MSCs as a compelling candidate as a therapeutic target. Immunomodulation by nontoxic neem leaf glycoprotein (NLGP) on dysfunctional cancer immunity offers significant therapeutic benefits to murine tumor host; however, its modulation on MSCs and its impact on T cell functions need to be elucidated. METHODS: Bone marrow-derived primary MSCs or murine 10 T1/2 MSCs were tumor-conditioned (TC-MSCs) and co-cultured with B16 melanoma antigen-specific DCs and MACS purified CD4+ and CD8+ T cells. T cell proliferation of T cells was checked by Ki67-based flow-cytometric and thymidine-incorporation assays. Cytokine secretion was measured by ELISA. The expression of cystathionase in DCs was assessed by RT-PCR. The STAT3/pSTAT3 levels in DCs were assessed by western blot, and STAT3 function was confirmed using specific SiRNA. Solid B16 melanoma tumor growth was monitored following adoptive transfer of conditioned CD8+ T cells. RESULTS: NLGP possesses an ability to restore anti-tumor T cell functions by modulating TC-MSCs. Supplementation of NLGP in DC-T cell co-culture significantly restored the inhibition in T cell proliferation and IFNγ secretion almost towards normal in the presence of TC-MSCs. Adoptive transfer of NLGP-treated TC-MSC supernatant educated CD8+ T cells in solid B16 melanoma bearing mice resulted in better tumor growth restriction than TC-MSC conditioned CD8+ T cells. NLGP downregulates IL-10 secretion by TC-MSCs, and concomitantly, pSTAT3 expression was downregulated in DCs in the presence of NLGP-treated TC-MSC supernatant. As pSTAT3 negatively regulates cystathionase expression in DCs, NLGP indirectly helps to maintain an almost normal level of cystathionase gene expression in DCs making them able to export sufficient amount of cysteine required for optimum T cell proliferation and effector functions within TME. CONCLUSIONS: NLGP could be a prospective immunotherapeutic agent to control the functions and behavior of highly immunosuppressive TC-MSCs providing optimum CD8+ T cell functions to showcase an important new approach that might be effective in overall cancer treatment.