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Contribution of arsenic and uranium in private wells and community water systems to urinary biomarkers in US adults: The Strong Heart Study and the Multi-Ethnic Study of Atherosclerosis.
Spaur, M, Glabonjat, RA, Schilling, K, Lombard, MA, Galvez-Fernandez, M, Lieberman-Cribbin, W, Hayek, C, Ilievski, V, Balac, O, Izuchukwu, C, et al
Journal of exposure science & environmental epidemiology. 2024;(1):77-89
Abstract
BACKGROUND Chronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). The contribution of water to total exposure is assumed to be low when water As and U concentrations are low. OBJECTIVE We examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban U.S. communities. METHODS We assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1485 and 6722 participants with dietary information and urinary biomarkers in the SHFS (2001-2003) and MESA (2000-2002; 2010-2011), respectively. Urine As was estimated as the sum of inorganic and methylated species, and urine U was total uranium. We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources via regression adjustment. RESULTS The median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a meta-analysis across both studies, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per twofold higher CWS As and U, respectively. In the SHFS, zip-code level factors such as private well and CWS As contributed 46% of variation in urine As, while in MESA, zip-code level factors, e.g., CWS As and U, contribute 30 and 49% of variation in urine As and U, respectively. IMPACT STATEMENT We found that water from unregulated private wells and regulated CWSs is a major contributor to urinary As and U (an estimated measure of internal dose) in both rural, American Indian populations and urban, racially/ethnically diverse populations nationwide, even at levels below the current regulatory standard. Our findings indicate that additional drinking water interventions, regulations, and policies can have a major impact on reducing total exposures to As and U, which are linked to adverse health effects even at low levels.
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A New Index of Insulin Sensitivity from Glucose Sensor and Insulin Pump Data: In Silico and In Vivo Validation in Youths with Type 1 Diabetes.
Schiavon, M, Galderisi, A, Basu, A, Kudva, YC, Cengiz, E, Dalla Man, C
Diabetes technology & therapeutics. 2023;(4):270-278
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Abstract
Background: Estimation of insulin sensitivity (SI) and its daily variation are key for optimizing insulin therapy in patients with type 1 diabetes (T1D). We recently developed a method for SI estimation from continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) data in adults with T1D (SISP) and validated it under restrained experimental conditions. Herein, we validate in vivo a new version of SISP performing well in daily life unrestrained conditions. Methods: The new SISP was tested in both simulated and real data. The simulated dataset consists of 100 virtual adults of the UVa/Padova T1D Simulator monitored during an open-loop experiment, whereas the real dataset consists of 10 youths with T1D monitored during a hybrid closed-loop meal study. In both datasets, participants underwent two consecutive meals (breakfast and lunch, at 7 and 11 am) with the same carbohydrate content (70 g). Plasma glucose and insulin were measured during each meal to estimate the oral glucose minimal model SI (SIMM). CGM and CSII data were used for SISP calculation, which was then validated against the gold standard SIMM. Results: SISP was estimated with good precision (median coefficient of variation <20%) in 100% of the real and 91% of the simulated meals. SISP and SIMM were highly correlated, both in the simulated and real datasets (R = 0.82 and R = 0.83, P < 0.001), and exhibited a similar intraday pattern. Conclusions: SISP is suitable for estimating SI in both closed- and open-loop settings, provided that the subject wears a CGM sensor and a subcutaneous insulin pump.
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Dietary Strawberries Improve Serum Metabolites of Cardiometabolic Risks in Adults with Features of the Metabolic Syndrome in a Randomized Controlled Crossover Trial.
Basu, A, Izuora, K, Hooyman, A, Scofield, HR, Ebersole, JL
International journal of molecular sciences. 2023;24(3)
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Plain language summary
Metabolic syndrome has been identified as a major risk factor for type 2 diabetes and its cardiovascular complications. Several dietary strategies, especially the use of different forms of dietary supplements, continue to be investigated for the prevention and management of this condition. The aim of this study was to examine the serum metabolites (targeted and untargeted) that may be affected by strawberry supplementation. This study was a randomised, double-blind, controlled crossover trial which enrolled adult participants with one or more features of metabolic syndrome. Participants were assigned to one of the three arms for four weeks separated by a one-week washout period. Results show that several targeted and untargeted serum metabolites were modulated with strawberry supplementation. In fact, strawberry supplementation improved the serum metabolic profiles which are associated with decreased risks of insulin resistance and diabetes, as well as endothelial dysfunction in adults with features of metabolic syndrome. Authors conclude that adding whole strawberries to the habitual diet may be a beneficial and feasible strategy to improve the cardiometabolic health in adults.
Abstract
Dietary strawberries have been shown to improve cardiometabolic risks in multiple clinical trials. However, no studies have reported effects on serum metabolomic profiles that may identify the target pathways affected by strawberries as underlying mechanisms. We conducted a 14-week randomized, controlled crossover study in which participants with features of metabolic syndrome were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, 1 serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were collected at baseline and at the end of each four-week phase of intervention. Serum samples were analyzed for primary metabolites and complex lipids using different mass spectrometry methods. Mixed-model ANOVA was used to examine differences in the targeted metabolites between treatment phases, and LASSO logistic regression was used to examine differences in the untargeted metabolites at end of the strawberry intervention vs. the baseline. The findings revealed significant differences in the serum branched-chain amino acids valine and leucine following strawberry intervention (high dose) compared with the low-dose and control phases. Untargeted metabolomic profiles revealed several metabolites, including serum phosphate, benzoic acid, and hydroxyphenyl propionic acid, that represented improved energy-metabolism pathways, compliance measures, and microbial metabolism of strawberry polyphenols, respectively. Thus, dietary supplementation of strawberries significantly improves the serum metabolic profiles of cardiometabolic risks in adults.
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Effects of an Eating Pattern Including Colorful Fruits and Vegetables on Management of Gestational Diabetes: A Randomized Controlled Trial.
Jaworsky, K, DeVillez, P, Alexander, JM, Basu, A
Nutrients. 2023;(16)
Abstract
Gestational diabetes mellitus (GDM), defined as abnormal glucose tolerance that presents during the second and third trimesters of pregnancy, is a growing issue in the United States and worldwide. If left untreated or poorly controlled, GDM can result in numerous consequences for both the mother and the fetus; thus, it is imperative that different avenues of management for GDM be explored. There is a paucity of studies that examine how lifestyle changes, including dietary and physical activity, affect management of GDM. We examined how counseling on lifestyle changes can affect cardiometabolic risks in women with GDM. We conducted a 12-week randomized controlled trial based on behavioral counseling in which women with GDM (N = 38) were randomized into either a nutrition education (control) (N = 18) group or nutrition intervention (N = 20) group. The nutrition education group were given dietary counseling regarding healthy dietary choices based on USDA guidelines, while the nutrition intervention group were instructed to consume a total of one cup of whole berries and one cup of leafy vegetables daily along with performing postprandial exercise (walking). Blood samples, anthropometric measures, and dietary and physical activity data, recorded in daily food and activity logs, were collected at baseline and at the end of the study and compared between the two groups. Dietary counseling on supplementation with whole berries and leafy vegetables resulted in increased fiber intake, increased antioxidant intake and total serum antioxidant capacity, improved random blood glucose, decreased serum IL-6, and improved HDL cholesterol versus the control group (all p < 0.05). These results highlight that whole berry and leafy vegetable supplementation-based dietary counseling can improve the metabolic pathways involved in gestational diabetes pathogenesis and prognosis. These functional foods must be recommended in the management of pregnancies affected by GDM.
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The Role of Phytochemicals and Plant-Based Diets in Gestational Diabetes: Evidence from Clinical Trials.
Jaworsky, K, DeVillez, P, Basu, A
International journal of environmental research and public health. 2023;(5)
Abstract
Gestational diabetes mellitus (GDM) is defined as glucose intolerance identified during pregnancy. The increased risk of pregnancy complications and the adverse health effects for the mother and baby associated with GDM require urgent and effective ways to control the condition. The primary goal of this semi-quantitative review was to examine the effects of phytochemicals and plant-based diets on GDM in clinical studies involving women undergoing pregnancy and to summarize the findings for application in clinical practice and disease management. The articles included in this review show that intervention strategies, including fruits, vegetables, whole grains, nuts and seeds, and tea, may be beneficial in the management of GDM and lower blood glucose and improve adverse pregnancy outcomes in these women. The randomized controlled trials reviewed collectively show improved glycemic control markers, blood lipid values, and body weight and composition when supplemented with phytochemical-rich supplements and foods compared to those in the control groups. The findings support the clinical observations of lower GDM risks in women consuming plant-derived diets rich in phytochemicals. Nutrition interventions involving plant-based foods and diets are thus a practical way to reduce hyperglycemia both in patients diagnosed with GDM and those at high risk for the development of GDM.
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The Effects of Plant-Derived Phytochemical Compounds and Phytochemical-Rich Diets on Females with Polycystic Ovarian Syndrome: A Scoping Review of Clinical Trials.
Chavez, GN, Jaworsky, K, Basu, A
International journal of environmental research and public health. 2023;(15)
Abstract
Polycystic ovarian syndrome (PCOS) is an endocrine condition that impacts nutritional status, metabolic, and hormonal function in females of reproductive age. This condition is associated with increased androgen production (hyperandrogenism) and decreased insulin sensitivity, which often leads to insulin resistance and hyperinsulinemia. This increase in androgen production and insulin resistance is strongly associated with a high incidence of obesity, type-2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and certain types of gonad-related cancers among females who suffer from this condition. As research continues to grow, it has been demonstrated that PCOS is a complex condition, and some of its characteristics vary among the females that have this disorder. However, it has been suggested that oxidative stress and low-grade chronic inflammation could play an important role in the development of PCOS. Current evidence suggest that phytochemicals could potentially help with weight-loss by reducing oxidative stress and low-grade inflammation, as well as aid in metabolic and hormonal regulation due to their antioxidant properties. Some of the bioactive compounds found in plants that have shown positive effects in the attenuation of PCOS include flavonoids, polyphenols, phytoestrogen, and polyunsaturated fatty acids (PUFAs). Thus, a review of the current literature published on PCOS and phytochemicals was conducted in PubMed, Google Scholar, and the Academy of Nutrition and Dietetics databases for articles published between 2013 and 2023 with a study duration of 1 to 3 months and adequate sample sizes. The main purpose of this review of literature was to investigate the metabolic effects of phytochemical compounds and phytochemical-rich diets on females with PCOS by comparing the results of several randomized clinical trials.
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Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.
Basu, A, Namporn, T, Ruenraroengsak, P
Pharmaceutics. 2023;(6)
Abstract
Hepatocellular carcinoma (HCC), accounting for 85% of liver cancer cases, continues to be the third leading cause of cancer-related deaths worldwide. Although various forms of chemotherapy and immunotherapy have been investigated in clinics, patients continue to suffer from high toxicity and undesirable side effects. Medicinal plants contain novel critical bioactives that can target multimodal oncogenic pathways; however, their clinical translation is often challenged due to poor aqueous solubility, low cellular uptake, and poor bioavailability. Nanoparticle-based drug delivery presents great opportunities in HCC therapy by increasing selectivity and transferring sufficient doses of bioactives to tumor areas with minimal damage to adjacent healthy cells. In fact, many phytochemicals encapsulated in FDA-approved nanocarriers have demonstrated the ability to modulate the tumor microenvironment. In this review, information about the mechanisms of promising plant bioactives against HCC is discussed and compared. Their benefits and risks as future nanotherapeutics are underscored. Nanocarriers that have been employed to encapsulate both pure bioactives and crude extracts for application in various HCC models are examined and compared. Finally, the current limitations in nanocarrier design, challenges related to the HCC microenvironment, and future opportunities are also discussed for the clinical translation of plant-based nanomedicines from bench to bedside.
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NLR family pyrin domain containing 3 (NLRP3) inflammasomes and peripheral neuropathic pain - Emphasis on microRNAs (miRNAs) as important regulators.
Basu, P, Maier, C, Averitt, DL, Basu, A
European journal of pharmacology. 2023;:175901
Abstract
Neuropathic pain is caused by the lesion or disease of the somatosensory system and can be initiated and/or maintained by both central and peripheral mechanisms. Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. Furthermore, we emphasize the effects of microRNAs as another regulator of NLRP3 inflammasome. In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions.
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Effect of Dietary Berry Supplementation on Antioxidant Biomarkers in Adults with Cardiometabolic Risks: A Systematic Review of Clinical Trials.
Helm, MM, Alaba, T, Klimis-Zacas, D, Izuora, K, Basu, A
Antioxidants (Basel, Switzerland). 2023;(6)
Abstract
Cardiometabolic conditions are closely associated with inflammation and oxidative stress. Dietary berries may serve as a beneficial nutrition intervention to address the features of cardiometabolic dysfunction and associated oxidative stress. The high antioxidant status of dietary berries may increase antioxidant capacity and reduce biomarkers of oxidative stress. This systematic review was conducted to investigate these effects of dietary berries. The search was conducted using PubMed, Cochrane Library, Web of Science, and citation searching. Through this search we identified 6309 articles and 54 were included in the review. Each study's risk of bias was assessed using the 2019 Cochrane Methods' Risk of Bias 2 tool. Antioxidant and oxidative stress outcomes were evaluated, and the magnitude of effect was calculated using Cohen's d. A range of effectiveness was reported in the included studies and the quality of the studies differed between the parallel and crossover trials. Considering the inconsistency in reported effectiveness, future investigations are warranted to determine the acute and sustained reductions of oxidative stress biomarkers from dietary berry intake (PROSPERO registration# CRD42022374654).
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The structure-function analysis of Obg-like GTPase proteins along the evolutionary tree from bacteria to humans.
Chakraborty, A, Halder, S, Kishore, P, Saha, D, Saha, S, Sikder, K, Basu, A
Genes to cells : devoted to molecular & cellular mechanisms. 2022;(7):469-481
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Abstract
Obg proteins belong to P-loop guanine triphosphatase (GTPase) that are conserved from bacteria to humans. Like other GTPases, Obg cycles between guanine triphosphate (GTP) bound "on" state and guanine diphosphate (GDP)-bound "off" state, thereby controlling various cellular processes. Different members of this group have unique structural characteristics; a conserved glycine-rich N-terminal domain known as obg fold, a central conserved nucleotide binding domain, and a less conserved C-terminal domain of other functions. Obg is a ribosome dependent GTPase helps in ribosome maturation by interacting with several proteins of the 50S subunit of the ribosome. Obg proteins have been widely considered as a regulator of cellular functions, helping in DNA replication, cell division. Apart from that, this protein also takes part in various stress adaptation pathways like a stringent response, sporulation, and general stress response. In this particular review, the structural features of ObgE have been highlighted and how the structure plays important role in interacting with regulators like GTP, ppGpp that are crucial for executing biological function has been orchestrated. In particular, we believe that Obg-like proteins can provide a link between different global pathways that are necessary for fine-tuning cellular processes to maintain the cellular energy status.