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Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis.
Kim, JS, Lee, G, Park, KI, Oh, SW
Diabetes & metabolism journal. 2024;(2):312-320
Abstract
BACKGRUOUND There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. RESULTS Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], -0.17; 95% confidence interval [CI], -0.27 to -0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. CONCLUSION SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.
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2.
Deciphering key factors in pathogen-suppressive microbiome assembly in the rhizosphere.
Andargie, YE, Lee, G, Jeong, M, Tagele, SB, Shin, JH
Frontiers in plant science. 2023;:1301698
Abstract
In a plant-microbe symbiosis, the host plant plays a key role in promoting the association of beneficial microbes and maintaining microbiome homeostasis through microbe-associated molecular patterns (MAMPs). The associated microbes provide an additional layer of protection for plant immunity and help in nutrient acquisition. Despite identical MAMPs in pathogens and commensals, the plant distinguishes between them and promotes the enrichment of beneficial ones while defending against the pathogens. The rhizosphere is a narrow zone of soil surrounding living plant roots. Hence, various biotic and abiotic factors are involved in shaping the rhizosphere microbiome responsible for pathogen suppression. Efforts have been devoted to modifying the composition and structure of the rhizosphere microbiome. Nevertheless, systemic manipulation of the rhizosphere microbiome has been challenging, and predicting the resultant microbiome structure after an introduced change is difficult. This is due to the involvement of various factors that determine microbiome assembly and result in an increased complexity of microbial networks. Thus, a comprehensive analysis of critical factors that influence microbiome assembly in the rhizosphere will enable scientists to design intervention techniques to reshape the rhizosphere microbiome structure and functions systematically. In this review, we give highlights on fundamental concepts in soil suppressiveness and concisely explore studies on how plants monitor microbiome assembly and homeostasis. We then emphasize key factors that govern pathogen-suppressive microbiome assembly. We discuss how pathogen infection enhances plant immunity by employing a cry-for-help strategy and examine how domestication wipes out defensive genes in plants experiencing domestication syndrome. Additionally, we provide insights into how nutrient availability and pH determine pathogen suppression in the rhizosphere. We finally highlight up-to-date endeavors in rhizosphere microbiome manipulation to gain valuable insights into potential strategies by which microbiome structure could be reshaped to promote pathogen-suppressive soil development.
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Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.
Christifano, DN, Crawford, SA, Lee, G, Brown, AR, Camargo, JT, Kerling, EH, Gajewski, BJ, Valentine, CJ, Gustafson, KM, DeFranco, EA, et al
Clinical nutrition ESPEN. 2023;53:93-99
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Plain language summary
Preterm birth (PTB) is the primary cause of infant mortality worldwide; and infants who survive have a higher risk of child disability. A recent Cochrane Review concluded that there is strong evidence that omega-3 fatty acids, especially docosahexaenoic acid (DHA), reduce early PTB (EPTB, <34 weeks gestation) and PTB (<37 weeks gestation) by 42% and 11%, respectively. The aim of this study was to investigate whether DHA intake at baseline alone could identify pregnancies for which high dose DHA supplementation lowered risk of EPTB and PTB. This study used the results from two randomised clinical trials of DHA supplementation during pregnancy in which participants completed the DHA-Food Frequency Questionnaire (FFQ) before randomisation to 200mg/day or high dose DHA, i.e., 800mg/day or 1000mg/day. A total of 1400 participants were enrolled in the two trials. Results show that the DHA-FFQ predicted participants whose risk of EPTB and PTB was reduced by consuming a DHA supplement of 800mg/day or 1000mg/day compared to 200mg/day. In fact, participants who started the study with an average daily DHA intake of <150mg had a 64% lower rate of EPTB and a 24% lower rate of PTB if they were assigned to 800mg/day or 1000mg/day compared to 200mg/day DHA. Authors conclude that the DHA-FFQ identifies women who could benefit from high dose DHA supplementation at least as effectively as a blood measure of DHA but with far fewer barriers for clinical implementation.
Abstract
BACKGROUND Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.
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ComQXPA quorum-sensing systems contribute to enhancing the protease activity of Bacillus velezensis DMB05 from fermented soybeans.
Na, HE, Heo, S, Kim, T, Lee, G, Lee, JH, Jeong, DW
International journal of food microbiology. 2023;:110294
Abstract
Bacillus velezensis DMB05, isolated from traditionally fermented soybean, meju, exhibited no protease activity on a TSA plate containing skim milk. To shed light on the genetic background behind this phenotypic non-protease activity, we analyzed the complete genome sequence of strain DMB05 and compared it with those of two B. velezensis strains which did exhibit protease activity. Comparative genome analyses showed no significant difference in the kind or number of proteases between the genomes of the three strains and that all strains possessed the degSU two-component system involved in the gene regulation of protease. However, strain DMB05 possessed a truncated comP which is part of the comQXPA operon that regulates the expression of degQ involved in the activation of DegSU. When the entire comQXPA operon derived from DMB06 was introduced into DMB05, the recombinant expressed proteolytic activity. The results of this experimental study provide evidence for the presence of regulatory genes involved in protease activity, one of several important factors involved in fermentation.
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Dietary regulations for microbiota dysbiosis among post-menopausal women with type 2 diabetes.
Singh, V, Park, YJ, Lee, G, Unno, T, Shin, JH
Critical reviews in food science and nutrition. 2023;(29):9961-9976
Abstract
Type 2 diabetes (T2D) and T2D-associated comorbidities, such as obesity, are serious universally prevalent health issues among post-menopausal women. Menopause is an unavoidable condition characterized by the depletion of estrogen, a gonadotropic hormone responsible for secondary sexual characteristics in women. In addition to sexual dimorphism, estrogen also participates in glucose-lipid homeostasis, and estrogen depletion is associated with insulin resistance in the female body. Estrogen level in the gut also regulates the microbiota composition, and even conjugated estrogen is actively metabolized by the estrobolome to maintain insulin levels. Moreover, post-menopausal gut microbiota is different from the pre-menopausal gut microbiota, as it is less diverse and lacks the mucolytic Akkermansia and short-chain fatty acid (SCFA) producers such as Faecalibacterium and Roseburia. Through various metabolites (SCFAs, secondary bile acid, and serotonin), the gut microbiota plays a significant role in regulating glucose homeostasis, oxidative stress, and T2D-associated pro-inflammatory cytokines (IL-1, IL-6). While gut dysbiosis is common among post-menopausal women, dietary interventions such as probiotics, prebiotics, and synbiotics can ease post-menopausal gut dysbiosis. The objective of this review is to understand the relationship between post-menopausal gut dysbiosis and T2D-associated factors. Additionally, the study also provided dietary recommendations to avoid T2D progression among post-menopausal women.
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Increased Production of γ-Aminobutyric Acid from Brewer's Spent Grain Through Bacillus Fermentation.
Kim, T, Heo, S, Na, HE, Lee, G, Lee, JH, Kim, JY, Jeong, DW
Journal of microbiology and biotechnology. 2023;(4):527-532
Abstract
Brewer's spent grain (BSG) is a waste product of the beer industry, and γ-aminobutyric acid (GABA) is a physiologically active substance important for brain and neuron physiology. In this study, we used the bacterial strains Bacillus velezensis DMB06 and B. licheniformis 0DA23-1, respectively, to ferment BSG and produce GABA. The GABA biosynthesis pathways were identified through genomic analysis of the genomes of both strains. We then inoculated the strains into BSG to determine changes in pH, acidity, reducing sugar content, amino-type nitrogen content, and GABA production, which was approximately doubled in BSG inoculated with Bacillus compared to that in uninoculated BSG; however, no significant difference was observed in GABA production between the two bacterial strains. These results provide the experimental basis for expanding the use of BSG by demonstrating the potential gain in increasing GABA production from a waste resource.
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Efficacy of deep learning-based artificial intelligence models in screening and referring patients with diabetic retinopathy and glaucoma.
Surya, J, Garima, , Pandy, N, Hyungtaek Rim, T, Lee, G, Priya, MNS, Subramanian, B, Raman, R
Indian journal of ophthalmology. 2023;(8):3039-3045
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Abstract
PURPOSE To analyze the efficacy of a deep learning (DL)-based artificial intelligence (AI)-based algorithm in detecting the presence of diabetic retinopathy (DR) and glaucoma suspect as compared to the diagnosis by specialists secondarily to explore whether the use of this algorithm can reduce the cross-referral in three clinical settings: a diabetologist clinic, retina clinic, and glaucoma clinic. METHODS This is a prospective observational study. Patients between 35 and 65 years of age were recruited from glaucoma and retina clinics at a tertiary eye care hospital and a physician's clinic. Non-mydriatic fundus photography was performed according to the disease-specific protocols. These images were graded by the AI system and specialist graders and comparatively analyzed. RESULTS Out of 1085 patients, 362 were seen at glaucoma clinics, 341 were seen at retina clinics, and 382 were seen at physician clinics. The kappa agreement between AI and the glaucoma grader was 85% [95% confidence interval (CI): 77.55-92.45%], and retina grading had 91.90% (95% CI: 87.78-96.02%). The retina grader from the glaucoma clinic had 85% agreement, and the glaucoma grader from the retina clinic had 73% agreement. The sensitivity and specificity of AI glaucoma grading were 79.37% (95% CI: 67.30-88.53%) and 99.45 (95% CI: 98.03-99.93), respectively; DR grading had 83.33% (95 CI: 51.59-97.91) and 98.86 (95% CI: 97.35-99.63). The cross-referral accuracy of DR and glaucoma was 89.57% and 95.43%, respectively. CONCLUSION DL-based AI systems showed high sensitivity and specificity in both patients with DR and glaucoma; also, there was a good agreement between the specialist graders and the AI system.
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Anti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: A case of finger millet.
Singh, V, Lee, G, Son, H, Amani, S, Baunthiyal, M, Shin, JH
Frontiers in nutrition. 2022;:1056445
Abstract
Finger millet (Eleusine coracana) is a staple food in several parts of the world because of its high nutritional value. In addition to its high nutrient content, finger millet contains numerous bioactive compounds, including polyphenol (10.2 mg/g TAE), flavonoid (5.54 mg/g CE), phytic acid (0.48%), and dietary fiber (15-20%). Polyphenols are known for their anti-oxidant and anti-diabetic role. Phytic acid, previously considered an anti-nutritive substance, is now regarded as a nutraceutical as it reduces carbohydrate digestibility and thus controls post-prandial glucose levels and obesity. Thus, finger millet is an attractive diet for patients with diabetes. Recent findings have revealed that the anti-oxidant activity and bio-accessibility of finger millet polyphenols increased significantly (P < 0.05) in the colon, confirming the role of the gut microbiota. The prebiotic content of finger millet was also utilized by the gut microbiota, such as Faecalibacterium, Eubacterium, and Roseburia, to generate colonic short-chain fatty acids (SCFAs), and probiotic Bifidobacterium and Lactobacillus, which are known to be anti-diabetic in nature. Notably, finger millet-induced mucus-degrading Akkermansia muciniphila can also help in alleviate diabetes by releasing propionate and Amuc_1100 protein. Various millet bio-actives effectively controlled pathogenic gut microbiota, such as Shigella and Clostridium histolyticum, to lower gut inflammation and, thus, the risk of diabetes in the host. In the current review, we have meticulously examined the role of gut microbiota in the bio-accessibility of millet compounds and their impact on diabetes.
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The Effect of Laminaria japonica on Metabolic Syndrome: A Systematic Review of Its Efficacy and Mechanism of Action.
Lee, IS, Ko, SJ, Lee, YN, Lee, G, Rahman, H, Kim, B
Nutrients. 2022;(15)
Abstract
Metabolic syndrome (MetS) is a medical condition characterized by abdominal obesity, insulin resistance, high blood pressure, and hyperlipidemia. An increase in the incidence of MetS provokes an escalation in health care costs and a downturn in quality of life. However, there is currently no cure for MetS, and the absence of immediate treatment for MetS has prompted the development of novel therapies. In accordance with recent studies, the brown seaweed Laminaria japonica (LJP) has anti-inflammatory and antioxidant properties, and so forth. LJP contains bioactive compounds used as food globally, and it has been used as a medicine in East Asian countries. We conducted a systematic review to examine whether LJP could potentially be a useful therapeutic drug for MetS. The following databases were searched from initiation to September 2021: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials Library. Clinical trials and in vivo studies evaluating the effects of LJP on MetS were included. LJP reduces the oxidative stress-related lipid mechanisms, inflammatory cytokines and macrophage-related chemokines, muscle cell proliferation, and migration. Bioactive-glucosidase inhibitors reduce diabetic complications, a therapeutic target in obesity and type 2 diabetes. In obesity, LJP increases AMP-activated protein kinase and decreases acetyl-CoA carboxylase. Based on our findings, we suggest that LJP could treat MetS, as it has pharmacological effects on MetS.
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Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.
Singh, V, Lee, G, Son, H, Koh, H, Kim, ES, Unno, T, Shin, JH
Frontiers in microbiology. 2022;:1103836
Abstract
Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.