Essential role of local antibody distribution in mediating bone-resorbing effects.

The link between antibodies and bone mass is debated. Activated IgG, which interacts directly with Fc gamma receptors, stimulates osteoclastogenesis in vitro, and local injection in immune-activated mice leads to bone loss. Multiple myeloma patients with high serum IgG levels have induced osteoclast activation and display bone loss. In addition, bone loss has been linked to serum autoantibodies in autoimmune diseases, including anti-citrullinated protein antibodies (ACPA) in individuals with rheumatoid arthritis (RA). Whether serum IgG or autoantibodies regulate bone mass under healthy conditions is poorly studied. In elderly men, neither serum levels of polyclonal IgG nor autoantibody were associated with areal bone mineral density in the MrOS Sweden study. Repetitive systemic injections of high-dose polyclonal IgG complexes in mice did not exert any discernible impact on bone mineral density. However, repetitive local intra-articular injection of the same IgG complexes led to a localized reduction of trabecular bone density. These results indicate antibodies may only impact bone density when close to the bone, such as within the synovial joint.

Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause.

Introduction: The glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation. Purpose: In this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations. Methods: Mice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies. Results: Using a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells. Conclusion: The study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Multimorbidity clusters and associated health care cost among patients attending psychiatric clinics in Odisha, India.

Introduction: There is a dearth of data on common multimorbidity clusters and the healthcare costs for individuals with mental health disorders. This study aimed to identify clinically meaningful physical-mental multimorbidity clusters, frequently occurring clusters of conditions, and healthcare utilization patterns and expenditure among patients attending a psychiatric outpatient clinic. Materials and Methods: Data were collected in the psychiatric outpatient department among patients aged 18 years and above in February-July 2019 (n = 500); follow-up data on non-communicable disease incidence were collected after 18 months. For analysis, morbidity clusters were defined using two approaches: 1) agglomerative hierarchical clustering method to identify clusters of diseases; and 2) non-hierarchical cluster k mean analysis to identify clusters of patients. Self-reported healthcare costs in these clusters were also calculated. Result: Two disease clusters were identified: using the 1st approach were; 1) hypertension, diabetes, and mood disorder; 2) Neurotic, stress-related, and somatoform disorders, and acid peptic disease. Three clusters of patients identified using the 2nd approach were identified: 1) those with mood disorders and cardiometabolic, musculoskeletal, and thyroid diseases; 2) those with neurotic, substance use, and organic mental disorders, cancer, and epilepsy; and 3) those with Schizophrenia. Patients in Cluster 1 were taking more than six medicines and had more hospital visits. Within 18 months, 41 participants developed either one or two chronic conditions, most commonly diabetes, hypertension, or thyroid disease. Conclusion: Cardiometabolic diseases are most commonly clustered with mood disorders. There is a need for blood pressure and sugar measurement in psychiatric clinics and mood disorder screening in cardiac, endocrinology, and primary care clinics.

Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.

Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 µg/mouse/day (low); 0.6 µg/mouse/day (medium)) or supraphysiological (6 µg/mouse/day (high)) doses of E2 (17ß-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (- 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (- 34% and - 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

Bazedoxifene does not share estrogens effects on IgG sialylation.

The incidence of rheumatoid arthritis (RA) increases at the same time as menopause when estrogen level decreases. Estrogen treatment is known to reduce the IgG pathogenicity by increasing the sialylation grade on the terminal glycan chain of the Fc domain, inhibiting the binding ability to the Fc gamma receptor. Therefore, treatment with estrogen may be beneficial in pre-RA patients who have autoantibodies and are prone to get an autoimmune disease. However, estrogen treatment is associated with negative side effects, therefore selective estrogen receptor modulators (SERMs) have been developed that have estrogenic protective effects with minimal side effects. In the present study, we investigated the impact of the SERM bazedoxifene on IgG sialylation as well as on total serum protein sialylation. C57BL6 mice were ovariectomized to simulate postmenopausal status, followed by ovalbumin immunization, and then treated with estrogen (estradiol), bazedoxifene, or vehicle. We found that estrogen treatment enhanced IgG levels and had a limited effect on IgG sialylation. Treatment with bazedoxifene increased the sialic acids in plasma cells in a similar manner to E2 but did not reach statistical significance. However, we did not detect any alteration in IgG-sialylation with bazedoxifene treatment. Neither estrogen nor bazedoxifene showed any significant alteration in serum protein sialylation but had a minor effect on mRNA expression of glycosyltransferase in the bone marrow, gonadal fat, and liver.

The role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy.

Immunotherapy has revolutionized cancer treatment and revitalized efforts to harness the power of the immune system to combat a variety of cancer types more effectively. However, low clinical response rates and differences in outcomes due to variations in the immune landscape among patients with cancer continue to be major limitations to immunotherapy. Recent efforts to improve responses to immunotherapy have focused on targeting cellular metabolism, as the metabolic characteristics of cancer cells can directly influence the activity and metabolism of immune cells, particularly T cells. Although the metabolic pathways of various cancer cells and T cells have been extensively reviewed, the intersections among these pathways, and their potential use as targets for improving responses to immune-checkpoint blockade therapies, are not completely understood. This review focuses on the interplay between tumor metabolites and T-cell dysfunction as well as the relationship between several T-cell metabolic patterns and T-cell activity/function in tumor immunology. Understanding these relationships could offer new avenues for improving responses to immunotherapy on a metabolic basis.

Comparison of three exercise interventions with and without gemcitabine treatment on pancreatic tumor growth in mice: No impact on tumor infiltrating lymphocytes.

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran at 12 m/min for 45 min and LVCE for 15 min, 5 days/week. HIIT ran 1-min at 20 m/min, followed by 1-min walking at 8 m/min for 20 total intervals, 3 days/week. SED did not run. Additional sets of inoculated mice were assigned to the exercise interventions but did not receive gemcitabine. Tumor volume was measured every other day for 2 weeks; tumor-infiltrating lymphocytes were assessed by flow cytometry 3-week post-inoculation. Results: Tumor growth did not differ between groups that received gemcitabine (F(3, 34) = 1.487; p = 0.235; η2 = 0.116). In contrast, tumor growth differed between groups not provided gemcitabine (F(3,14) = 3.364; p = 0.049, η2 = 0.419), with trends for slower growth in LVCE than SED (p = 0.088) and HIIT (p = 0.084). Groups did not differ in tumor infiltrating lymphocytes. Conclusion: Contrary to our hypotheses, the exercise interventions compared here did not further reduce pancreatic tumor growth beyond that provided by gemcitabine. However, in mice not receiving gemcitabine, there was a trend for reduced tumor growth in LVCE.

Human (but not animal) motion can be recognized at first sight - After treatment for congenital blindness.

The long-standing nativist vs. empiricist debate asks a foundational question in epistemology - does our knowledge arise through experience or is it available innately? Studies that probe the sensitivity of newborns and patients recovering from congenital blindness are central in informing this dialogue. One of the most robust sensitivities our visual system possesses is to 'biological motion' - the movement patterns of humans and other vertebrates. Various biological motion perception skills (such as distinguishing between movement of human and non-human animals, or between upright and inverted human movement) become evident within the first months of life. The mechanisms of acquiring these capabilities, and specifically the contribution of visual experience to their development, are still under debate. We had the opportunity to directly examine the role of visual experience in biological motion perception, by testing what level of sensitivity is present immediately upon onset of sight following years of congenital visual deprivation. Two congenitally blind patients who underwent sight-restorative cataract-removal surgery late in life (at the ages of 7 and 20 years) were tested before and after sight restoration. The patients were shown displays of walking humans, pigeons, and cats, and asked to describe what they saw. Visual recognition of movement patterns emerged immediately upon eye-opening following surgery, when the patients spontaneously began to identify human, but not animal, biological motion. This recognition ability was evident contemporaneously for upright and inverted human displays. These findings suggest that visual recognition of human motion patterns may not critically depend on visual experience, as it was evident upon first exposure to un-obstructed sight in patients with very limited prior visual exposure, and furthermore, was not limited to the typical (upright) orientation of humans in real-life settings.

Development of Visual Memory Capacity Following Early-Onset and Extended Blindness.

It is unknown whether visual memory capacity can develop if onset of pattern vision is delayed for several years following birth. We had an opportunity to address this question through our work with an unusual population of 12 congenitally blind individuals ranging in age from 8 to 22 years. After providing them with sight surgery, we longitudinally evaluated their visual memory capacity using an image-memorization task. Our findings revealed poor visual memory capacity soon after surgery but significant improvement in subsequent months. Although there may be limits to this improvement, performance 1 year after surgery was found to be comparable with that of control participants with matched visual acuity. These findings provide evidence for plasticity of visual memory mechanisms into late childhood but do not rule out vulnerability to early deprivation. Our computational simulations suggest that a potential mechanism to account for changes in memory performance may be progressive representational elaboration in image encoding.

Effect of exercise on pancreatic cancer patients during treatment: a scoping review of the literature.

INTRODUCTION: Exercise can lower the risk of developing pancreatic cancer and has the potential to improve physical fitness and quality of life in patients with the disease. Yet, the effects of exercise training during pancreatic cancer treatment remain poorly characterized. This hampers the development of evidence-based disease-specific exercise recommendations. PURPOSE: The purpose of this review was to describe and interpret the effect of exercise on physiological, QoL, and cancer-specific outcomes reported in clinical trials among pancreatic cancer patients during treatment. METHODS: We conducted a scoping review of the literature according to the framework proposed by Arksey and O'Malley. Articles published prior to December 2021 were retrieved from PubMed, EMBASE, and Scopus. We only included studies that prescribed structured cardiorespiratory and/or resistance exercise in pancreatic cancer patients undergoing treatment. RESULTS: A total of 662 references were retrieved, of which 24 are included in the review. Twelve articles were randomized controlled trials and 12 were single-arm trials. Overlap in the trials from which data were reported occurred in 16 articles. Moderate intensity exercise was most commonly prescribed, reported feasible for most patients, with potential to enhance physical fitness and QoL. However, exercise adherence and beneficial effects may diminish with disease progression. Limited evidence suggests exercise may benefit cancer-specific outcomes. CONCLUSION: The results of this review indicate that exercise is feasible during pancreatic cancer treatment. Exercise can also improve physical fitness and QoL. However, its beneficial effects may fall with advanced disease and more rigorous research is needed to develop precise exercise protocols for this population.

A tissue-selective estrogen complex as treatment of osteoporosis in experimental lupus.

Osteoporosis is a common secondary complication in patients with systemic lupus erythematosus (SLE). Current osteoporosis treatment with bisphosphonates has some negative side effects and there is a lack of data regarding newer treatments options for SLE associated osteoporosis. The tissue-selective estrogen complex (TSEC) containing conjugated estrogens and the selective estrogen receptor modulator bazedoxifene (Bza) is approved for treatment of postmenopausal vasomotor symptoms and prevention of osteoporosis. However, it has not been evaluated for treatment of osteoporosis in postmenopausal SLE patients. Ovariectomized MRL/lpr mice constitute a model for postmenopausal lupus that can be used for osteoporosis studies. We used this model in a set of experiments where the mice were treated with different doses of 17ß-estradiol-3-benzoate (E2), Bza, or TSEC (E2 plus Bza), administered in the early or late phases of disease development. The skeleton was analyzed by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and high-resolution microcomputed tomography. The lupus disease was assessed by determination of proteinuria, hematuria, and lupus disease markers in serum. Treatment with medium dose TSEC administered in early disease protected ovariectomized MRL/lpr mice from trabecular bone loss, while there were no differences in lupus disease parameters between treatments. This is the first experimental study to investigate TSEC as a potential new therapy for osteoporosis in postmenopausal SLE.

Effectiveness of an mHealth-Based Electronic Decision Support System for Integrated Management of Chronic Conditions in Primary Care: The mWellcare Cluster-Randomized Controlled Trial.

BACKGROUND: The burden of noncommunicable diseases and their risk factors has rapidly increased worldwide, including in India. Innovative management strategies with electronic decision support and task sharing have been assessed for hypertension, diabetes mellitus, and depression individually, but an integrated package for multiple chronic condition management in primary care has not been evaluated. METHODS: In a prospective, multicenter, open-label, cluster-randomized controlled trial involving 40 community health centers, using hypertension and diabetes mellitus as entry points, we evaluated the effectiveness of mWellcare, an mHealth system consisting of electronic health record storage and an electronic decision support for the integrated management of 5 chronic conditions (hypertension, diabetes mellitus, current tobacco and alcohol use, and depression) versus enhanced usual care among patients with hypertension and diabetes mellitus in India. At trial end (12-month follow-up), using intention-to-treat analysis, we examined the mean difference between arms in change in systolic blood pressure and glycated hemoglobin as primary outcomes and fasting blood glucose, total cholesterol, predicted 10-year risk of cardiovascular disease, depression score, and proportions reporting tobacco and alcohol use as secondary outcomes. Mixed-effects regression models were used to account for clustering and other confounding variables. RESULTS: Among 3698 enrolled participants across 40 clusters (mean age, 55.1 years; SD, 11 years; 55.2% men), 3324 completed the trial. There was no evidence of difference between the 2 arms for systolic blood pressure (Δ=-0.98; 95% CI, -4.64 to 2.67) and glycated hemoglobin (Δ=0.11; 95% CI, -0.24 to 0.45) even after adjustment of several key variables (adjusted differences for systolic blood pressure: - 0.31 [95% CI, -3.91 to 3.29]; for glycated hemoglobin: 0.08 [95% CI, -0.27 to 0.44]). The mean within-group changes in systolic blood pressure in mWellcare and enhanced usual care were -13.65 mm Hg versus -12.66 mm Hg, respectively, and for glycated hemoglobin were -0.48% and -0.58%, respectively. Similarly, there were no differences in the changes between the 2 groups for tobacco and alcohol use or other secondary outcomes. CONCLUSIONS: We did not find an incremental benefit of mWellcare over enhanced usual care in the management of the chronic conditions studied. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02480062.

High adenovirus 36 seroprevalence among a population of Hispanic American youth.

Infection with adenovirus 36 (Ad36) has been associated with risk of obesity in youth in some studies, but the seroprevalence of this virus has not been examined among all populations. As Hispanic-American youth are of greater risk for obesity than other American youth, we sought to determine the proportion of Ad36 seropositive (Ad36+) students in an urban middle school serving a Hispanic population. We further examined if Ad36+ students were more likely to have obesity, and if Ad36 serostatus impacted changes in weight status following a health intervention. We determined body mass index (BMI) at the beginning and end of a 16-week health intervention among 40 Hispanic-American middle-school students. Ad36 serostatus was determined by enzyme-linked immunsorbent assay (ELISA). Seventy percent of the students were Ad36+. Ad36+ and Ad36 seronegative (Ad36-) did not differ before or after the intervention in body weight measures. The odds of being classified as obese was 1.4 times greater among Ad36+ than Ad36- at baseline, and 2.4 times greater post-intervention, but these were not statistically significant. We report a high seroprevalence of Ad36 among a population of Hispanic-American students. Ad36 seropositivity was associated with a trend for a greater likelihood of having obesity, but did not impact response to a health intervention.

Autologous serum collected 1 h post-exercise enhances natural killer cell cytotoxicity.

Natural Killer cells are cytotoxic lymphocytes that recognize and eliminate tumor cells. Exercise enhances NK cell cytotoxic activity (NKCA), yet the underlying mechanisms are not fully understood. Exercise-induced shifts in NK-cell subsets has been proposed as one mechanism. Alternatively, exercise alters stress hormone and cytokine levels, which are also known to affect NKCA. AIM: Determine the role(s) of exercise-induced shifts in the proportions of NK-cell subsets found in the blood, and changes in serum IL-2, IL-6, IL-12, IFN-γ, TNF-α and cortisol, on exercise-induced changes in NKCA. METHODS: Twelve adults cycled 30 min at 115% of their lactate threshold power. Peripheral blood mononuclear cells (PBMCs) and serum were isolated from blood collected pre-, post-, and 1 h post-exercise. To investigate the effect of shifts in NK-cell subsets, pre-, post- and 1 h post-exercise NK cells were incubated with target cells (K562 and U266) in the presence of autologous pre-exercise serum. The effects of hormones and cytokines released during exercise were determined by incubating pre-exercise PBMCs with tumor target cells (K562 and U266) in the presence of pre-, post-, and 1 h post-exercise serum. NKCA and phenotypes were assessed by flow cytometry. RESULTS: Although exercise mobilized high-differentiated NK cell subsets (NKG2A-/KIR+), NKCA per cell was not altered post-exercise in the presence of pre-exercise serum. Conversely, 1 h post-exercise serum significantly increased the cytotoxicity of pre-exercise NK cells against HLA-expressing target cells (U266). This increase associated with lower levels of cortisol, and occurred when serum contained higher levels of IFN-γ. CONCLUSIONS: Exercise-induced shifts in NK-cell subsets did not fully explain changes in NKCA. Rather, factors present in serum during exercise recovery enhanced NKCA against target cells. Our results suggest lower cortisol and higher IFN-γ levels may explain exercise-induced changes in NKCA.

Protocol for the mWellcare trial: a multicentre, cluster randomised, 12-month, controlled trial to compare the effectiveness of mWellcare, an mHealth system for an integrated management of patients with hypertension and diabetes, versus enhanced usual care in India.

INTRODUCTION: Rising burden of cardiovascular disease (CVD) and diabetes is a major challenge to the health system in India. Innovative approaches such as mobile phone technology (mHealth) for electronic decision support in delivering evidence-based and integrated care for hypertension, diabetes and comorbid depression have potential to transform the primary healthcare system. METHODS AND ANALYSIS: mWellcare trial is a multicentre, cluster randomised controlled trial evaluating the clinical and cost-effectiveness of a mHealth system and nurse managed care for people with hypertension and diabetes in rural India. mWellcare system is an Android-based mobile application designed to generate algorithm-based clinical management prompts for treating hypertension and diabetes and also capable of storing health records, sending alerts and reminders for follow-up and adherence to medication. We recruited a total of 3702 participants from 40 Community Health Centres (CHCs), with ≥90 at each of the CHCs in the intervention and control (enhanced care) arms. The primary outcome is the difference in mean change (from baseline to 1 year) in systolic blood pressure and glycated haemoglobin (HbA1c) between the two treatment arms. The secondary outcomes are difference in mean change from baseline to 1 year in fasting plasma glucose, total cholesterol, predicted 10-year risk of CVD, depression, smoking behaviour, body mass index and alcohol use between the two treatment arms and cost-effectiveness. ETHICS AND DISSEMINATION: The study has been approved by the institutional Ethics Committees at Public Health Foundation of India and the London School of Hygiene and Tropical Medicine. Findings will be disseminated widely through peer-reviewed publications, conference presentations and other mechanisms. TRIAL REGISTRATION: mWellcare trial is registered with Clinicaltrial.gov (Registration number NCT02480062; Pre-results) and Clinical Trial Registry of India (Registration number CTRI/2016/02/006641). The current version of the protocol is Version 2 dated 19 October 2015 and the study sponsor is Public Health Foundation of India, Gurgaon, India (www.phfi.org).

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds.

The Wnt signaling pathways play pivotal roles in carcinogenesis. Modulation of the cell-surface abundance of Wnt receptors is emerging as an important mechanism for regulating sensitivity to Wnt ligands. Endocytosis and degradation of the Wnt receptors Frizzled (Fzd) and lipoprotein-related protein 6 (LRP6) are regulated by the E3 ubiquitin ligases zinc and ring finger 3 (ZNRF3) and ring finger protein 43 (RNF43), which are disrupted in cancer. In a genome-wide small interfering RNA screen, we identified the deubiquitylase ubiquitin-specific protease 6 (USP6) as a potent activator of Wnt signaling. USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance. Chromosomal translocations in nodular fasciitis result in USP6 overexpression, leading to transcriptional activation of the Wnt/ß-catenin pathway. Inhibition of Wnt signaling using Dickkopf-1 (DKK1) or a Porcupine (PORCN) inhibitor significantly decreased the growth of USP6-driven xenograft tumors, indicating that Wnt signaling is a key target of USP6 during tumorigenesis. Our study defines an additional route to ectopic Wnt pathway activation in human disease, and identifies a potential approach to modulate Wnt signaling for therapeutic benefit.

Preliminary nutritional and biological potential of Artocarpus heterophyllus L. shell powder.

Artocarpus heterophyllus shell powder was investigated in terms of its nutritional and biological potential. A thorough examination of shell powder demonstrated its potential as a source of minerals, ß carotene and dietary fiber, which were assessed gravimetrically & spectrophotometrically. This showed 3.05 ± 0.19 g 100 g(-1) DW of alkaloids followed by saponins and tannins. Three different extracts; acetone, methanol, & mix solvent were used to evaluate phenolic & flavonoid content, antioxidant & antimicrobial activity, GC/MS screening and quantitative analysis of polyphenols. Among all, the methanol extract showed highest antioxidant activity evaluated by DPPH, FRAP & ABTS assays and was significantly correlated with phenolic and flavonoid contents. Phenolic & flavonoid content was found to be 158 ± 0.34 mg (GAE) and 10.0 ± 0.64 mg (CE) respectively. The results of antimicrobial activity showed that L. monocytogenes was more susceptible to all extracts followed by other microorganisms. Catechin, ascorbic & chlorogenic acids were identified as major polyphenols analyzed by LC-MS/MS. GC/MS analysis showed that it contains a variety of compounds with different therapeutic activities. The study revealed that A. heterophyllus shell is a good source of natural antioxidants & other bioactive compounds and can be used in cosmetics, medicines and functional food application.