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1.
Effects of a dietary intervention on cardiometabolic risk and food consumption in a workplace.
Shrestha, A, Tamrakar, D, Ghinanju, B, Shrestha, D, Khadka, P, Adhikari, B, Shrestha, J, Waiwa, S, Pyakurel, P, Bhandari, N, et al
PloS one. 2024;(4):e0301826
Abstract
BACKGROUND Worksite-based health programs have shown positive impacts on employee health and have led to significant improvements in cardiovascular risk factor profiles. We aimed to determine the effect of cafeteria intervention on cardio-metabolic risk factors diet in a worksite setting (Dhulikhel Hospital) in Nepal. METHODS In this one-arm pre-post intervention study, we recruited 277 non-pregnant hospital employees aged 18-60 with prediabetes or pre-hypertension. The study was registered in clinicaltrials.gov (NCT03447340; 2018/02/27). All four cafeterias in the hospital premises received cafeteria intervention encouraging healthy foods and discouraging unhealthy foods for six months. We measured blood pressure, fasting glucose level, glycated hemoglobin, cholesterol in the laboratory, and diet intake (in servings per week) using 24-hour recall before and six months after the intervention. The before and after measures were compared using paired-t tests. RESULTS After six months of cafeteria intervention, the median consumption of whole grains, mono/polyunsaturated fat, fruits, vegetable and nuts servings per week increased by 2.24(p<0.001), 2.88(p<0.001), 0.84(p<0.001) 2.25(p<0.001) and nuts 0.55 (p<0.001) servings per week respectively. The median consumption of refined grains decreased by 5.07 servings per week (p<0.001). Mean systolic and diastolic blood pressure decreased by 2 mmHg (SE = 0.6; p = 0.003) and 0.1 mmHg (SE = 0.6; p = 0.008), respectively. The low-density lipoprotein (LDL) was significantly reduced by 6 mg/dL (SE = 1.4; p<0.001). CONCLUSION Overall, we found a decrease in consumption of refined grains and an increase in consumption of whole grains, unsaturated fats, fruits, and nuts observed a modest reduction in blood pressure and LDL cholesterol following a 6-month cafeteria-based worksite intervention incorporating access to healthy foods.
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Individual patient-centered target-driven intervention to improve clinical outcomes of diabetes, health literacy, and self-care practices in Nepal: A randomized controlled trial.
Pardhan, S, Upadhyaya, T, Smith, L, Sharma, T, Tuladhar, S, Adhikari, B, Kidd, J, Sapkota, R
Frontiers in endocrinology. 2023;:1076253
Abstract
PURPOSE To examine the effectiveness of a culturally and linguistically appropriate, patient-centered, target-driven lifestyle intervention with video education training in improving clinical outcomes, health literacy, and diabetic self-care practices in newly diagnosed patients in Nepal. METHODS A total of 110 participants with newly and consequently diagnosed Type 2 were randomly allocated into intervention (mean age = 45 ± 9.7 years) and control (mean age = 47 ± 12.5 years) groups. Intervention group participants were trained on a culturally and linguistically appropriate diabetic video education program and were given a customized dietary and physical activity plan with specific targets to practice at home. Participants' compliance was monitored weekly via telephone calls. Both groups received the usual treatment from their doctor and were followed up after three months. Outcome measures included changes in: i. diabetic health literacy, diet, and physical activity measured using self-reported questionnaires; and ii. blood glucose (glycated hemoglobin, HbA1c), cholesterol, blood pressure, body mass index, and visual acuity. Clinical outcome measures were blinded from randomization and intervention allocation. RESULTS After three months, HbA1c decreased to 6.1% from the baseline value of 7.2% in the intervention group compared to 6.6% in the control group from the baseline value of 7.1% (p <0.05). The intervention group had mean total cholesterol and low-density lipoprotein of 174 and 95.5 mg/dL, which were significantly lower than 186 and 107.5 mg/dL in the control group. Daily white rice consumption decreased by 36.5% in the intervention vs. 4% in the control group (p <0.05). After three months, the intervention group participants exercised more than the control group (p <0.05). All intervention group participants self-initiated retinal screening checks since the baseline visit among which 13% showed early diabetic retinopathy signs compared to 0% in the control group. Health literacy improvement in the intervention group was found to be sustained after three months too. CONCLUSIONS A culturally appropriate, target-driven lifestyle intervention with video education training is effective in improving clinical outcomes, health literacy, and self-care practice in newly diagnosed diabetic patients in Nepal, i.e., at a time period when effective diabetes control is vital to prevent further complications. The training intervention could be rolled out nationwide in order to reduce the risk of diabetic-related complications and improve people's quality of life and productivity.
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Nostoc sphaeroides Cyanobacteria: a review of its nutritional characteristics and processing technologies.
Zhu, S, Xu, J, Adhikari, B, Lv, W, Chen, H
Critical reviews in food science and nutrition. 2023;(27):8975-8991
Abstract
Nostoc sphaeroides is an edible Cyanobacterium which has high nutritional value and is widely used in dietary supplements and therapeutic products. N. sphaeroides contains protein, fatty acid, minerals and vitamins. Its polysaccharides, phycobilin, phycobiliproteins and some lipids are highly bioactive. Thus, N. sphaeroides possesses anti-oxidation, anti-inflammation and cholesterol reducing functions. This paper reviews and evaluates the literature on nutritionally and functionally important compounds of N. sphaeroides. It also reviews and evaluates the processing of technologies used to process N. sphaeroides from fresh harvest to dry particulates including pretreatment, sterilization and drying, including their impact on sensorial and nutritional values. This review shows that a suitable combination of ultrasound, radio frequency and pulse spouted microwave with traditional sterilization and drying technologies greatly improves the sensorial and nutritive quality of processed N. sphaeroides and improves their shelf life; however, further research is needed to evaluate these hybrid technologies. Once suitably processed, N. sphaeroides can be used in food, cosmetics and pharmaceutical drugs as an ingredient.
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Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?
Chen, Y, Qie, X, Quan, W, Zeng, M, Qin, F, Chen, J, Adhikari, B, He, Z
Critical reviews in food science and nutrition. 2023;(20):4288-4324
Abstract
Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.
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Computational Modeling of Macrophage Iron Sequestration during Host Defense against Aspergillus.
Adhikari, B, Scindia, Y, Sordo Vieira, L, de Assis Lopes Ribeiro, H, Masison, J, Yang, N, Fonseca, LL, Wheeler, M, Knapp, AC, Mei, Y, et al
mSphere. 2022;(4):e0007422
Abstract
Iron is essential to the virulence of Aspergillus species, and restricting iron availability is a critical mechanism of antimicrobial host defense. Macrophages recruited to the site of infection are at the crux of this process, employing multiple intersecting mechanisms to orchestrate iron sequestration from pathogens. To gain an integrated understanding of how this is achieved in aspergillosis, we generated a transcriptomic time series of the response of human monocyte-derived macrophages to Aspergillus and used this and the available literature to construct a mechanistic computational model of iron handling of macrophages during this infection. We found an overwhelming macrophage response beginning 2 to 4 h after exposure to the fungus, which included upregulated transcription of iron import proteins transferrin receptor-1, divalent metal transporter-1, and ZIP family transporters, and downregulated transcription of the iron exporter ferroportin. The computational model, based on a discrete dynamical systems framework, consisted of 21 3-state nodes, and was validated with additional experimental data that were not used in model generation. The model accurately captures the steady state and the trajectories of most of the quantitatively measured nodes. In the experimental data, we surprisingly found that transferrin receptor-1 upregulation preceded the induction of inflammatory cytokines, a feature that deviated from model predictions. Model simulations suggested that direct induction of transferrin receptor-1 (TfR1) after fungal recognition, independent of the iron regulatory protein-labile iron pool (IRP-LIP) system, explains this finding. We anticipate that this model will contribute to a quantitative understanding of iron regulation as a fundamental host defense mechanism during aspergillosis. IMPORTANCE Invasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. To understand how recruited macrophages mediate iron deprivation during the infection, we developed and validated a mechanistic computational model that integrates the available information in the field. The insights provided by this approach can help in designing iron modulation therapies as anti-fungal treatments.
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6.
Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome.
Ribeiro, HA, Vieira, LS, Scindia, Y, Adhikari, B, Wheeler, M, Knapp, A, Schroeder, W, Mehrad, B, Laubenbacher, R
Journal of the Royal Society, Interface. 2022;(189):20210806
Abstract
Aspergillus species are ubiquitous environmental moulds, with spores inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address it, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validated in vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate seems to be an essential prerequisite for the establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability and impaired leucocyte activation lead to a high conidial germination rate. Similarly, in neutropenic hosts, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leucocyte activation and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition and leucocyte activation as critical determinants of the fate of the infection.
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Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review.
Adhikari, B, Marasini, BP, Rayamajhee, B, Bhattarai, BR, Lamichhane, G, Khadayat, K, Adhikari, A, Khanal, S, Parajuli, N
Phytotherapy research : PTR. 2021;(3):1298-1312
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Abstract
The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.
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Potential natural inhibitors of xanthine oxidase and HMG-CoA reductase in cholesterol regulation: in silico analysis.
Marahatha, R, Basnet, S, Bhattarai, BR, Budhathoki, P, Aryal, B, Adhikari, B, Lamichhane, G, Poudel, DK, Parajuli, N
BMC complementary medicine and therapies. 2021;(1):1
Abstract
BACKGROUND Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates' requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. METHODS Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. RESULTS The molecular docking of amentoflavone (GOLD score 70.54, ∆G calc. = - 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ∆G calc. = - 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6' → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. CONCLUSION This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.
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Fermentation transforms the phenolic profiles and bioactivities of plant-based foods.
Leonard, W, Zhang, P, Ying, D, Adhikari, B, Fang, Z
Biotechnology advances. 2021;:107763
Abstract
Phenolics are a group of compounds derived from plants that have displayed potent biological activities and health-promoting effects. Fermentation is one of the most conventional but still prevalent bioprocessing methods in the food industry, with the potential to increase phenolic content and enhance its nutritive value. This review details the biotransformation of different classes of phenolics (hydroxycinnamic and hydroxybenzoic acids, flavonoids, tannins, stilbenoids, lignans, alkylresorcinols) by various microorganisms (lactic acid bacteria, yeast, filamentous fungi) throughout the fermentation process in plant-based foods. Several researchers have commenced the use of metabolic engineering, as in recombinant Saccharomyces cerevisiae yeast and Escherichia coli, to enhance the production of this transformation. The impact of phenolics on the metabolism of microorganisms and fermentation process, although complex, is reviewed for the first time. Moreover, this paper highlights the general effect of fermentation on the food's phenolic content, and its bioaccessibility, bioavailability and bioactivities including antioxidant capacity, anti-cancer, anti-diabetic, anti-inflammation, anti-obesity properties. Phenolics of different classes are converted into compounds that are often more bioactive than the parent compounds, and fermentation generally leads to a higher phenolic content and antioxidant activity in most studies. However, biotransformation of several phenolic classes is less studied due to its low concentration and apparent insignificance to the food system. Therefore, there is potential for application of metabolic engineering to further enhance the content of different phenolic classes and bioactivities in food.
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Trans-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta (Aβ42) and Protect from Aβ42 Induced Oxidative Damage in Yeast Models of Alzheimer's Disease.
Dhakal, S, Ramsland, PA, Adhikari, B, Macreadie, I
International journal of molecular sciences. 2021;(17)
Abstract
Finding an effective therapeutic to prevent or cure AD has been difficult due to the complexity of the brain and limited experimental models. This study utilized unmodified and genetically modified Saccharomyces cerevisiae as model organisms to find potential natural bioactive compounds capable of reducing intracellular amyloid beta 42 (Aβ42) and associated oxidative damage. Eleven natural bioactive compounds including mangiferin, quercetin, rutin, resveratrol, epigallocatechin gallate (EGCG), urolithin A, oleuropein, rosmarinic acid, salvianolic acid B, baicalein and trans-chalcone were screened for their ability to reduce intracellular green fluorescent protein tagged Aβ42 (GFP-Aβ42) levels. The two most effective compounds from the screens were combined in varying concentrations of each to study the combined capacity to reduce GFP-Aβ42. The most effective combinations were examined for their effect on growth rate, turnover of native Aβ42 and reactive oxygen species (ROS). The bioactive compounds except mangiferin and urolithin A significantly reduced intracellular GFP-Aβ42 levels. Baicalein and trans-chalcone were the most effective compounds among those that were screened. The combination of baicalein and trans-chalcone synergistically reduced GFP-Aβ42 levels. A combination of 15 μM trans-chalcone and 8 μM baicalein was found to be the most synergistic combination. The combination of the two compounds significantly reduced ROS and Aβ42 levels in yeast cells expressing native Aβ42 without affecting growth of the cells. These findings suggest that the combination of baicalein and trans-chalcone could be a promising multifactorial therapeutic strategy to cure or prevent AD. However, further studies are recommended to look for similar cytoprotective activity in humans and to find an optimal dosage.