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Bortezomib-induced neuropathic pain (BINP) poses a challenge in multiple myeloma (MM) treatment. Genetic factors play a key role in BINP susceptibility, but research has predominantly focused on Caucasian populations. This research explored novel genetic risk loci and pathways associated with BINP development in Korean MM patients while evaluating the reproducibility of variants from Caucasians. Clinical data and buffy coat samples from 185 MM patients on bortezomib were collected. The cohort was split into discovery and validation cohorts through random stratification of clinical risk factors for BINP. Genome-wide association study was performed on the discovery cohort (n = 74) with Infinium Global Screening Array-24 v3.0 BeadChip (654,027 single nucleotide polymorphism [SNPs]). Relevant biological pathways were identified using the pathway scoring algorithm. The top 20 SNPs were validated in the validation cohort (n = 111). Previously reported SNPs were validated in the entire cohort (n = 185). Pathway analysis of the genome-wide association study results identified 31 relevant pathways, including immune systems and endosomal vacuolar pathways. Among the top 20 SNPs from the discovery cohort, 16 were replicated, which included intronic variants in ASIC2 and SMOC2, recently implicated in nociception, as well as intergenic variants or long noncoding RNAs. None of the 17 previously reported SNPs remained significant in our cohort (rs2274578, P = .085). This study represents the first investigation of novel genetic loci and biological pathways associated with BINP occurrence. Our findings, in conjunction with existing Caucasian studies, expand the understanding of personalized risk prediction and disease mechanisms. PERSPECTIVE: This article is the first to explore novel genetic loci and pathways linked to BINP in Korean MM patients, offering novel insights beyond the existing research focused on Caucasian populations into personalized risk assessment and therapeutic strategies of BINP.
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Bortezomib , Estudo de Associação Genômica Ampla , Neuralgia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Bortezomib/efeitos adversos , Estudos de Coortes , Predisposição Genética para Doença , Mieloma Múltiplo/genética , Mieloma Múltiplo/tratamento farmacológico , Neuralgia/genética , Neuralgia/induzido quimicamente , República da Coreia , Fatores de Risco , População do Leste Asiático/genéticaRESUMO
CD19 Chimeric antigen receptor T (CAR-T) cell therapy has shown a promising response rate for relapsed/refractory B-cell malignancies. However, serious side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome arose in early case reports. Though several preclinical and clinical studies of CAR-T cell therapy have been reported, there is a lack of toxicological assessments. This study was carried out as a preclinical assessment of CD19 CAR-T cell therapy, including the anti-leukemic efficacy, kinetics in peripheral blood, and 4-week single-dose toxicity evaluation in leukemia xenograft mice. Leukemia xenograft mice model was established by injecting 1.0 × 105 cells/mouse of luciferase-labeled human B cell acute lymphoblastic leukemia (B-ALL) cell line via the tail vein, and after 3 days, 2.0 or 4.0 × 106 cells/mouse of CD19 CAR-T cells were injected intravenously. CD19 CAR-T cells showed significant anti-leukemic efficacy, showing inhibition of tumor progression in the bioluminescence-based in-vivo imaging system. In the kinetics study using qPCR, CAR-T cells peaked in peripheral blood on day 60 in males and day 30 in females. In a 4-week single-dose toxicity study, CD19 CAR-T cell injected groups showed no mortality and toxicological signs, or changes in body weight, food/water consumption, hematology, clinical chemistry, organ weights, and histopathology compared to control groups. These results suggested that 4.0 × 106 cells/mouse of CD19 CAR-T cells were effective in B-ALL xenograft mice without serious side effects, so the no-observed adverse effect level (NOAEL) was estimated to be higher than 4.0 × 106 cells/mouse, under the condition examined in the current study.
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Linfoma de Burkitt , Leucemia , Receptores de Antígenos Quiméricos , Masculino , Feminino , Humanos , Camundongos , Animais , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Xenoenxertos , Cinética , Linfoma de Burkitt/tratamento farmacológico , Leucemia/tratamento farmacológico , Antígenos CD19 , Terapia Baseada em Transplante de Células e TecidosRESUMO
Integration site (IS) analysis is essential in ensuring safety and efficacy of gene therapies when integrating vectors are used. Although clinical trials of gene therapy are rapidly increasing, current methods have limited use in clinical settings because of their lengthy protocols. Here, we describe a novel genome-wide IS analysis method, "detection of the integration sites in a time-efficient manner, quantifying clonal size using tagmentation sequencing" (DIStinct-seq). In DIStinct-seq, a bead-linked Tn5 transposome is used, allowing the sequencing library to be prepared within a single day. We validated the quantification performance of DIStinct-seq for measuring clonal size with clones of known IS. Using ex vivo chimeric antigen receptor (CAR)-T cells, we revealed the characteristics of lentiviral IS. We then applied it to CAR-T cells collected at various times from tumor-engrafted mice, detecting 1,034-6,233 IS. Notably, we observed that the highly expanded clones had a higher integration frequency in the transcription units and vice versa in genomic safe harbors (GSH). Also, in GSH, persistent clones had more frequent IS. Together with these findings, the new IS analysis method will help to improve the safety and efficacy of gene therapies.
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Little is known regarding Korean preschooler dietary phytochemical index (DPIs). We used the 24 h recall data of 1196 participants aged 3-5 years from the Korea National Health and Nutrition Examination Survey to study the association between dietary food intake and obesity prevalence. The amount of dietary intake by food group was compared according to sex and DPI quartile. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. The average total DPI and energy from phytochemical food groups were not significantly different according to sex, although boys had a higher total daily food intake. Different inclinations between DPI quartiles and amount of intake were observed in the food groups; specifically, beans showed a higher intake difference between Q1 and Q4 for boys than in the other food groups. The highest DPI quartile had a significantly lower obesity prevalence than the lowest DPI quartile in all models for boys only when obesity prevalence by weight percentile was analyzed (Model 3, OR: 0.287, 95% CI: 0.095-0.868, p for trend < 0.05). Our results suggest a high DPI could help prevent obesity in preschoolers.
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Obesidade , Compostos Fitoquímicos , Masculino , Humanos , Inquéritos Nutricionais , Prevalência , Obesidade/epidemiologia , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. AIM: We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. METHODS: Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. RESULTS: In total, 479 patients were analyzed, with a median observation period of 50 months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14 mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3 mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). CONCLUSION: Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.
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Carcinoma Ductal Pancreático , Cisto Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia , Fatores de Risco , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Neoplasias PancreáticasRESUMO
PURPOSE: This study aimed to investigate changes in physical activity and energy intake according to abdominal obesity in Korean adult men before and after COVID-19. METHODS: Using data from the 2019 and 2020 KNHANES, the physical activity level measured by the Global Physical Activity Questionnaire (GPAQ) the physical activity level by GPAQ, number of days of walking and strength training, aerobic exercise, and total energy, protein, fat, carbohydrate, dietary fiber, and sugar intake for a total of 2,799 participants were analyzed. RESULTS: There were no changes in energy intake during the pandemic. The number of days of weekly walking was higher (2019, p = 0.006; 2020, p = 0.012) and strength training was significantly higher (2019, p < 0.0001; 2020 p < 0.0001) in the non-abdominal obesity group than in the abdominal obesity group before and after COVID-19. Strength training at least once a week suppressed abdominal obesity (0.628 times in 2019, p < 0.0001; 0.605 times in 2020, p < 0.0001). In addition, even when the total energy intake and age were adjusted for, strength training influenced the suppression of abdominal obesity (0.634 times in 2019, p < 0.0001; 0.614 times in 2020, p < 0.0001). CONCLUSION: Even with the change in the physical activity level, such as walking and aerobic exercise, due to the influence of social distancing measures, strength training influenced the suppression of abdominal obesity, regardless of the COVID-19 pandemic.
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Objective Treatment for uncomplicated diverticulitis (UD) is not well established. We evaluated the strategy of reviewing intravenous antibiotics for hospitalized Japanese patients with UD. Methods Treatment was based on the physician's choice until August 2018; the indications for hospitalization and treatment have been standardized since September 2018. In this study, we monitored the use of intravenous antibiotics administered to patients hospitalized for UD and then reviewed the need for them on hospital day 3. We compared patients' length of antibiotic use, hospital stay, health care cost, and complications via the review strategy from September 2018 to December 2020 and via the previous physicians' choice strategy from January 2016 to August 2018. Results Two hundred and forty-seven patients were admitted to our hospital because of acute colonic diverticulitis from January 2016 to December 2020. After excluding complicated cases, 106 individuals were enrolled during the period of physician's choice; 87 were enrolled when treatment review was employed. There were no significant differences in age, sex, inflammation site, or severity during the first hospital visit. The median duration of antibiotic use was significantly reduced from 5 to 4 days (p=0.0075), with no marked increase in rates of transfer to surgery, mortality, or readmission due to recurrence. A more significant proportion of patients completed 3-day antibiotic treatment with the review strategy than with the physician's choice strategy (6.6% vs. 25.3%, p=0.0004). However, the length of hospital stay and total medical costs did not decrease. Conclusion The strategy of reviewing treatment on day 3 after hospitalization for UD safety reduced the duration of antibiotic use, but the hospital stay and health care costs did not decrease.
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Doença Diverticular do Colo , Diverticulite , Humanos , Antibacterianos/efeitos adversos , Japão , Doença Aguda , Diverticulite/tratamento farmacológico , Diverticulite/complicações , Doença Diverticular do Colo/tratamento farmacológico , Resultado do TratamentoRESUMO
The purpose of the current study was to examine the effect of adding secondary ingredients such as green tea derived water-soluble polysaccharides (GTP) and flavonol aglycone rich fractions derived from cellulase treated green tea extract (FVN) into catechin rich green tea extracts (GTE) on wheat starch digestion and intestinal glucose transport using in vitro digestion with Caco-2 cells. Co-digestion of wheat starch with GTE (16.88 g L-1) or GTE + GTP + FVN (16.69 g L-1) appeared to promote starch hydrolysis compared to control (15.49 g L-1). In case of major flavonoids, addition of epigallocatechin gallate (EGCG), EGCG + myricetin (M) into wheat starch significantly increased the digestion of starch into glucose. Glucose transport rate decreased by 22.35% in wheat starch + GTE + GTP + FVN (1.39%), while the least amount of glucose (1.70%) was transported in EGCG mixed with M (1% of EGCG) as secondary ingredients among individual flavonoids formulation. It indicated that inhibitory effect on glucose transport was higher in addition of GTE, GTP, and FVN as excipients ingredients rather than targeted major flavonoids. Results from the current study suggest that whole green tea including flavonoid rich fractions could enhance hypoglycemic potential of GTE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05140-2.
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Background: There is a substantial gap in the eating behaviors between the sexes. We aimed to analyze the predictors of eating behaviors by sex in the young adult population. Methods: We used the data of the sixth and seventh Korea National Health and Nutrition Examination Survey conducted by the Korea Disease Control and Prevention Agency last 2013-2018. Data from 2,502 women and 2,101 men aged 19-29 yr were included in the analysis using frequency, percentage, x 2-test, and multiple logistic regression. Results: Education (0.612, CI=0.465â¼0.805), economic status (2.104, CI=1.435-3.086), marital status (3.162, CI=2.356â¼4.243), and household structure (0.403, CI=0.208â¼0.782) were identified to predict the frequency of dining-out in women, while marital status (0.302, CI=0.121â¼0.749), economic activity (1.969, CI=1.483â¼2.613), and household structure (0.243, CI=0.137â¼0.432) predicted dining-out frequency in men. The current smoking status predicted most eating behaviors, including breakfast skipping frequency (1.864, CI=1.318â¼2.637), use of supplements (2.062, CI=1.439â¼2.953), and use of nutrition labels (1.545, 1.084â¼2.204) for men. Meanwhile, nutrition labeling was used less in both men (0.550, CI=0.343â¼0.882) and women (0.646, CI=0.473â¼0.882) who subjective body recognition as obesity. Conclusion: The factors that primarily predicted the frequency of dining out in young women and the behavior of breakfast skipping, use of nutrition labels, and frequency of dining-out in men can be used as foundational data for developing sex-specific intervention programs to improve eating behaviors.
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BACKGROUND: Asivatrep is a potent and selective antagonist of transient receptor potential vanilloid subfamily V member 1 (TRPV1), which plays an important role in itch and inflammation in atopic dermatitis (AD). OBJECTIVE: This current study aimed to evaluate the efficacy and safety of asivatrep cream in patients with AD. METHODS: For this phase 3 double-blind, vehicle-controlled study, patients aged ≥12 years with mild to moderate AD were enrolled and randomly assigned 2:1 to the 1.0% asivatrep or vehicle group for 8 weeks of twice-daily application (n = 240). The primary end point was the proportion of patients with an Investigator's Global Assessment score (IGA) of 0 or 1 at week 8. Standard safety assessments were conducted. RESULTS: At week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1 (P < .001); significantly more had ≥2 points of improvement on the IGA from baseline score (20.3% vs 7.7%; P = .01). The mean percentage reduction in the Eczema Area and Severity Index (EASI) score was 44.3% for the asivatrep group and 21.4% for the vehicle group at week 8 (P < .001). Significantly more asivatrep-treated patients experienced an improvement of at least 50%, 75%, and 90% on the EASI than the vehicle group. The mean ± SD change in the pruritus visual analog scale score at week 8 was -2.3 ± 2.4 for the asivatrep group and -1.5 ± 2.4 for the vehicle group (P = .02). No significant safety issues were reported. CONCLUSION: Asivatrep improved clinical signs and symptoms of AD and was well tolerated.
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Dermatite Atópica , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Emolientes/uso terapêutico , Excipientes , Humanos , Imunoglobulina A , Prurido/tratamento farmacológico , Índice de Gravidade de Doença , Canais de Cátion TRPV , Resultado do TratamentoRESUMO
Hypertriglyceridemia, a symptom of elevated triglyceride level in the blood, is a potent risk factor for cardiovascular and metabolic disorders. Among the numerous treatments to regulate circulating triglyceride levels, fibrates are widely used to treat hypertriglyceridemia, although they also have side effects such as hepatotoxicity and gallstone formation. In the present study, we aimed to investigate the blood triglyceride-lowering effects of a naturally fermented green tea extract (NFGT) and the underlying mechanisms on hypertriglyceridemia in vitro and in vivo models. NFGT suppressed the expression of lipogenic genes, while augmented expression of fatty acid oxidation-related genes in cultured cells, leading to the significant decrease of intracellular triglyceride content. NFGT treated group in fructose-induced hypertriglyceridemic rat model significantly decreased plasma and hepatic triglyceride, which was accompanied by an increase in excretion of fecal fat. Taken together, we propose that NFGT could be potentially a novel functional ingredient to prevent or treat hypertriglyceridemia.
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The purpose of the current study was to investigate the effect of green tea ethanol extract (GTE) and polysaccharide fractions from green tea (PFGs) on the hydrolysis of wheat starch, microstructural changes, and intestinal transport of glucose. The amount of resistant starch (RS) was significantly lowered in the water-soluble polysaccharide (WSP), water-soluble polysaccharide-pectinase (WSP-P), and water-insoluble polysaccharide-alkali soluble (WISP-Alk-Soluble; p < 0.05). The microstructures of gelatinized wheat starch granules with WSP, WSP-P, and WISP-Alk-Soluble were spherical with small cracks. The amount of intestinal transported glucose from digested wheat starch was 2.12-3.50 times lower than the control group. The results from the current study suggest that water- and alkali-soluble PFGs could be potential ingredients to lower starch hydrolysis as well as to control the postprandial blood glucose level when foods that contain starch are consumed.
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Amido , Chá , Glucose , Hidrólise , Polissacarídeos , TriticumRESUMO
In South Korea, domestic cattle, pigs, and goats were subjected to mandatory foot-and-mouth disease (FMD) vaccination and year-round serosurveillance since 2011. In 2020, approximately USD 95 million was spent solely for FMD vaccine purchase for 59 million livestock, and 1.25 million samples were tested to estimate the population immunity and demonstrate the absence of virus circulation. As the FMD vaccination program was revised in 2018, the post-vaccination monitoring (PVM) was designed to evaluate the effectiveness of the vaccine program of three vaccines approved for routine use. To this end, monitoring post-vaccination immunity has been conducted by collecting 35,626 serum samples at 28 days post-vaccination following regular national vaccinations, which were carried out in April and in October in 2020. The design of the serological test for PVM was specially targeted at particular livestock groups, including dairy cattle, goats, and beef cattle aged 6-12 months, which were generally estimated to have a low expected seroprevalence. The risk factors had also been identified, considering the increased likelihood of infection in a particular location, herd size, and husbandry system applied in a targeted sample collection. Serum sample collection and SP-O and NSP antibody tests were performed by local veterinary laboratories using commercially available ELISAs. The current FMD vaccination program, which was performed twice a year following the regimen of primary vaccination and boost, resulted in over 80% population immunity. The seroprevalence monitored after the vaccination in fall was higher than the one studied in spring except in pigs. It was demonstrated that the seroprevalence of risk-based targeted samples ranged from 93.8 to 100% in cattle, 63.2 to 100% in pigs, and 20.0 to 100% in goats. Of note is the area near the North Korean borders which showed a relatively low seroprevalence among the targeted regions, and no NSP sero-positive reactor was detected in this region. When subpopulation immunity at the individual level was assessed, the seroprevalence in young cattle stock was slightly lower (95.8%) than that of adults (98.4%). In conclusion, the FMD vaccination campaign has been successfully implemented in Korea, and the PVM can be a supplementary program for massive routine surveillance in terms of providing timely information needed both to estimate population immunity and to properly target "risk-based surveillance."
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The aim of this study was to profile the bioaccessibility and intestinal absorption of epicatechins and flavonols in different forms of green tea and its formulation: loose leaf tea, powdered tea, 35% catechins containing GTE, and GTE formulated with green tea-derived polysaccharide and flavonols (CATEPLUS™). The bioaccessibillity and intestinal absorption of epicatechins and flavonols was investigated by using an in vitro digestion model system with Caco-2 cells. The bioaccessibility of total epicatechins in loose leaf tea, powdered tea, GTE, and CATEPLUS™ was 1.27%, 2.30%, 22.05%, and 18.72%, respectively, showing that GTE and CATEPLUS™ had significantly higher bioaccessibility than powdered tea and loose leaf tea. None of the flavonols were detected in powdered tea and loose leaf tea, but the bioaccessibility of the total flavonols in GTE and CATEPLUS™ was 85.74% and 66.98%, respectively. The highest intestinal absorption of epicatechins was found in CATEPLUS™ (171.39 ± 5.39 ng/mg protein) followed by GTE (57.38 ± 9.31), powdered tea (3.60 ± 0.67), and loose leaf tea (2.94 ± 1.03). The results from the study suggest that formulating green tea extracts rich in catechins with second components obtained from green tea processing could enhance the bioavailability of epicatechins.
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Flavonoides/farmacologia , Chá/metabolismo , Antioxidantes , Disponibilidade Biológica , Transporte Biológico , Células CACO-2 , Catequina/química , Catequina/metabolismo , Digestão/efeitos dos fármacos , Digestão/fisiologia , Flavonoides/metabolismo , Flavonóis/química , Flavonóis/metabolismo , Humanos , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Modelos Biológicos , Extratos VegetaisRESUMO
Airborne fine dust particles (FDPs) have been identified as major toxins in air pollution that threaten human respiratory health. While searching for an anti-FDP reagent, we found that green tea extract (GTE) and fractions rich in flavonol glycosides (FLGs) and crude tea polysaccharides (CTPs) had protective effects against FDP-stimulated cellular damage in the BEAS-2B airway epithelial cell line. The GTE, FLGs, and CTPs significantly increased viability and lowered oxidative stress levels in FDP-treated cells. Combined treatment with GTE, FLGs, and CTPs also exerted synergistic protective effects on cells and attenuated FDP-induced elevations in inflammatory gene expression. Moreover, the green tea components increased the proportion of ciliated cells and upregulated ciliogenesis in the airway in FDP-stimulated BEAS-2B cells. Our findings provide insights into how natural phytochemicals protect the airway and suggest that green tea could be used to reduce FDP-induced airway damage as an ingredient in pharmaceutical, nutraceutical, and also cosmeceutical products.
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Catequina/uso terapêutico , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Chá/química , Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cílios/efeitos dos fármacos , Cílios/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Trillions of microorganisms reside in the hosts' gut. Since diverse activities of gut microbiota affect the hosts' health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.
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Akkermansia/crescimento & desenvolvimento , Catequina/análogos & derivados , Microbioma Gastrointestinal , Chá/química , Akkermansia/efeitos dos fármacos , Animais , Catequina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Although tacrolimus (FK-506) has been shown to be an effective monotherapy for psoriasis, it does not always work well. Currently, combination therapy is frequently used to manage psoriasis because clinical trials have shown it may provide additive or synergistic benefits and reduce risks of adverse effects. Myeloid-derived suppressor cells (MDSCs) have potent immunomodulatory and anti-inflammatory properties in autoimmune diseases. We previously reported that MDSCs had protective effects in a murine model of imiquimod (IMQ)-induced psoriasis. The present study was undertaken to investigate the systemic immunomodulatory and therapeutic efficacy effects of MDSC plus FK-506 in an IMQ-induced mouse model of psoriasis and to investigate the immunomodulatory mechanisms involved. Systemic MDSC plus FK-506 therapy was found to have a significant anti-psoriatic effect in the murine model, to reduce levels of pro-inflammatory cytokines Th1 cytokines (TNF-α and IFN-γ) and Th17 cytokines (IL-17A and IL-23) in serum and skin. However, treatment with MDSCs or FK-506 alone had little impact. Furthermore, the anti-psoriatic effects of MDSC plus FK-506 were associated with histopathological reductions in inflammatory infiltration, epidermal hyperplasia, and hyperkeratosis. In addition, this combined treatment also attenuated IMQ-induced splenomegaly, and increased the proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells and decreased the proportions of CD4+IFN-γ+ Th1 cells and CD4+IL-17+ Th17 cells in spleen. Taken together, our results show systemic combination therapy with MDSCs and FK-506 had a better therapeutic effect in our IMQ-induced psoriasis model than either agent alone, and suggest that this combinatorial therapy might be useful for the management of autoimmune skin diseases like psoriasis.
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Imunossupressores/farmacologia , Células Supressoras Mieloides/imunologia , Psoríase/tratamento farmacológico , Tacrolimo/farmacologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Imiquimode/toxicidade , Imunomodulação/efeitos dos fármacos , Imunossupressores/uso terapêutico , Camundongos Endogâmicos C57BL , Psoríase/induzido quimicamente , Psoríase/patologia , Pele/metabolismo , Pele/patologia , Baço/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Tacrolimo/uso terapêutico , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacosRESUMO
BACKGROUND: Water soluble polysaccharide derived from green tea (WSP) is produced as byproducts when catechins were extracted from green tea. Although inhibitory effect of green tea catechins on the glucose transport in small intestine has been studied, the hypoglycemic efficacy of the WSP or its combinational effect has not been studied. In order to investigate hypoglycemic efficacy of the WSP or its combinational effect with green tea extract (GTE), co-consumption of GTE and WSP with wheat starch was investigated using in vitro digestion coupled with Caco-2 cells. The mechanism of the intestinal glucose transport was elucidated throughout the gene expression of the intestinal glucose transporters, which included sodium dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The co-digestion of wheat starch with GTE during the small intestinal phase was the most rapidly digested into reducing sugar (73.96 g L-1 ) compared to itself (48.44 g L-1 ), WSP (60.35 g L-1 ), and GTE + WSP (61.81 g L-1 ). Intestinal glucose transport was 11.82, 7.59, 4.49, and 2.40% for wheat starch, wheat starch with GTE, WSP, and GTE + WSP, respectively. The highest decreased expression pattern in SGLT1 was observed when cells treated with wheat starch + GTE + WSP (0.66-fold) compared to GTE or WSP treatment. CONCLUSION: The results suggested that co-consumption of green tea derived products with wheat starch could delay the intestinal absorption of glucose. Results from the current study suggested that GTE and WSP could be the useful supplements of dietary therapy for hyperglycemia to delay glucose absorption. © 2020 Society of Chemical Industry.
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Camellia sinensis/metabolismo , Catequina/metabolismo , Glucose/metabolismo , Hipoglicemiantes/metabolismo , Mucosa Intestinal/metabolismo , Extratos Vegetais/metabolismo , Polissacarídeos/metabolismo , Transporte Biológico , Células CACO-2 , Camellia sinensis/química , Humanos , Amido/metabolismo , Chá/química , Chá/metabolismoRESUMO
It was revealed that excipient ingredients such as flavonols (FVN) or polysaccharides (GTP) which could be derived from green tea enhanced catechin absorption. We hypothesized that the addition of FVN or GTP as excipient ingredients into epicatechin rich green tea extracts (GTE) may improve the health benefits that accompany its consumption. When FVN8.7 (8.7% of GTE, w/w) was added to the GTE (20 mg) as an excipient ingredient, the bioaccessibility and intestinal absorption of total epicatechins was 1.2 and 1.5 times higher than that of only GTE, respectively. This was due to the free radical scavenging capacity of flavonols, showing 114.23 ± 3.07 µmol TE per g for GTE 100 + FVN8.7 and 113.64 ± 1.61 µmol TE per g for GTE 100 + FVN2, respectively. This was significantly higher than the GTE or GTE 100 + OW2 (onion peel and whangchil extracts, 2% of GTE, w/w) which have the same amount of total flavonols. Regarding potential hypoglycemic effects, co-digestion of GTE (20 mg) + green tea polysaccharides (2 mg) + FVN (5 mg) with wheat starch significantly reduced glucose intestinal absorption by 41.85 ± 1.75% compared to only the wheat starch. The results from the current study suggest that whole green tea components rich in flavonols and polysaccharides could be potential hypoglycemic excipient ingredients for green tea catechins.
Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Catequina/farmacologia , Excipientes/farmacologia , Flavonóis/farmacologia , Radicais Livres/metabolismo , Polissacarídeos/farmacologia , Chá/química , Antioxidantes/farmacologia , Disponibilidade Biológica , Transporte Biológico , Células CACO-2 , Camellia sinensis , Humanos , Cebolas , Extratos Vegetais/farmacologia , AmidoRESUMO
Obese individuals are considered to have lower energy expenditure (EE) rates than non-obese individuals. We aimed to investigate the effects of various factors related to food intake on diet-induced thermogenesis (DIT) in the EE of obese individuals. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed relevant literature from PubMed, Embase, and Medline databases from study inception till the end of July 2019. Studies on dietary factors affecting DIT in obese individuals were included. Fifteen studies were included; these studies assessed macronutrient, single-nutrient, or supplement meal compositions, as well as dietary patterns and behaviors. The effect of obesity on DIT was not constant in each study. Differences in DIT pertained to the protein ratio being higher than the fat ratio or the carbohydrate ratio being higher than the fat ratio. High intake of calcium and vitamin D as well as high-oleic peanut supplements increased DIT in obese people. In addition, ascorbic acid intake, fatty acid saturation, and the chain length of various fatty acids had no effects on DIT. In conclusion, the findings suggest that in obese individuals, DIT is associated with various factors related to meal, nutrient, and dietary habits. However, because of the complexity of the relationship between DIT and obesity, it is difficult to determine the critical element underlying this association.