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1.
Effect and mechanism of quercetin or quercetin-containing formulas against COVID-19: From bench to bedside.
Chen, JY, Huang, TR, Hsu, SY, Huang, CC, Wang, HS, Chang, JS
Phytotherapy research : PTR. 2024
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic since 2019. Immunopathogenesis and thromboembolic events are central to its pathogenesis. Quercetin exhibits several beneficial activities against COVID-19, including antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic effects. Although several reviews have been published, these reviews are incomplete from the viewpoint of translational medicine. The authors comprehensively evaluated the evidence of quercetin against COVID-19, both basically and clinically, to apply quercetin and/or its derivatives in the future. The authors searched the PubMed, Embase, and the Cochrane Library databases without any restrictions. The search terms included COVID-19, SARS-CoV-2, quercetin, antiviral, anti-inflammatory, immunomodulatory, thrombosis, embolism, oxidative, and microbiota. The references of relevant articles were also reviewed. All authors independently screened and reviewed the quality of each included manuscript. The Cochrane Risk of Bias Tool, version 2 (RoB 2) was used to assess the quality of the included randomized controlled trials (RCTs). All selected studies were discussed monthly. The effectiveness of quercetin against COVID-19 is not solid due to methodological flaws in the clinical trials. High-quality studies are also required for quercetin-containing traditional Chinese medicines. The low bioavailability and highly variable pharmacokinetics of quercetin hinder its clinical applications. Its positive impact on immunomodulation through reverting dysbiosis of gut microbiota still lacks robust evidence. Quercetin against COVID-19 does not have tough clinical evidence. Strategies to improve its bioavailability and/or to develop its effective derivatives are needed. Well-designed RCTs are also crucial to confirm their effectiveness in the future.
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2.
Supplementation with Lactiplantibacillus brevis GKEX Combined with Resistance Exercise Training Improves Muscle Mass, Strength Performance, and Body Fat Condition in Healthy Humans.
Lee, MC, Hsu, YJ, Ho, CS, Tsai, YS, Chen, CC, Huang, CC
Foods (Basel, Switzerland). 2024;(7)
Abstract
In addition to maintaining good exercise and dietary habits, recent studies have shown that probiotics may have potential benefits for muscle mass and strength. It is worth noting that the effects may vary depending on the specific strains used. To date, no studies have analyzed the effects of Lactiplantibacillus brevis in this context. Here, we combine the L. brevis strain GKEX with resistance training to further understand its effects on muscle mass, thickness, performance, and fat loss. In a six-week intervention for a double-blind randomized trial, 52 healthy subjects were divided into two groups (10 male and 16 female participants in each group): a placebo group (two capsules/day, containing 0 CFU of GKEX per capsule) and a GKEX group (two capsules/day, containing 1 × 1010 CFU of GKEX per capsule). Before the intervention, no differences were observed between the two groups in any of the tests (body composition, muscle thickness, exercise performance, and blood parameters). However, supplementation with GKEX significantly improved muscle mass and thickness, as well as grip strength, muscle strength, and explosive performance, when compared to the associated parameters before the intervention. Additionally, GKEX supplementation promoted a reduction in the body fat percentage (p < 0.05). Through analysis of the change amount, we observed that GKEX supplementation yielded significantly improved benefits when compared to the placebo group (p < 0.05). In summary, our findings support the notion that a six-week resistance exercise training program combined with L. brevis GKEX supplementation has superior additive effects that enhance muscle mass and strength performance, while also reducing body fat percentage. This intervention can promote muscle gain and fat loss.
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3.
A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial.
Lee, MC, Hsu, YJ, Shen, SY, Ho, CS, Huang, CC
International journal of medical sciences. 2023;(10):1272-1281
Abstract
B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide energy, each B vitamin acts as a cofactor in energy metabolism processes. Based on the evidence presented above, we hypothesized that a 28-day supplementation of vitamin B would enhance physical performance and reduce physical fatigue. The objective of this study was to evaluate the anti-fatigue effect of vitamin B supplementation, specifically vitamin B1, B2, B6, and B12, and its potential to improve exercise performance. We employed a randomized double-blind crossover design with a 28-day supplementation period. Sixteen male and sixteen female subjects, aged 20-30 years, were divided into two groups: the placebo group (n=16, equal gender distribution) and the Ex PLUS® group (n=16, equal gender distribution). The participants received either placebo or Ex PLUS® (one tablet per day) for 28 consecutive days. Following the intervention, there was a 14-day wash-out period during which the subjects did not receive any further interventions. After supplementation with Ex PLUS®, we found a significant increase in the running time by 1.26-fold (p < 0.05) to exhaustion compared to that before supplementation and that in the placebo group. In addition, the Ex PLUS® supplementation group presented significantly reduced blood lactate and blood ammonia concentrations during exercise and at rest after exercise compared with placebo (p < 0.05). In conclusion, 28 consecutive days of vitamin B complex (Ex PLUS®) supplementation significantly improved exercise endurance performance and reduced exercise fatigue biochemical metabolites in not athletes. In addition, it does not cause adverse effects in humans when taken at appropriate doses.
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4.
Renal function during hospitalization and outcome in Chinese patients with acute decompensated heart failure: A retrospective study and literature review.
Lee, HW, Huang, CC, Yang, CY, Leu, HB, Huang, PH, Wu, TC, Lin, SJ, Chen, JW
Clinical cardiology. 2023;(1):57-66
Abstract
BACKGROUND The heart and kidneys had demonstrated a bidirectional interaction that dysfunction of the heart or kidneys can induce dysfunction in the other organ. HYPOTHESIS Renal function and its decline during hospitalization may have impact on cardiovascular outcomes in patients with acute decompensated heart failure (ADHF). METHODS A total of 119 consecutive Chinese patients admitted for ADHF were prospectively enrolled. The course of renal function was presented with estimated glomerular filtration rate (eGFR), calculated by the four-variable equation proposed by the Modification of Diet in Renal Disease (MDRD) Study. Worsening renal function (WRF) was defined as eGFR decline between admission (eGFRadmission ) and predischarge (eGFRpredischarge ). Clinical outcomes were defined as 4P-major adverse cardiovascular events (4P-MACE), including the composition of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal HF hospitalization. RESULTS During an average 2.6 ± 3.2 years follow-up, 66 patients (55%) experienced 4P-MACE. Patients with impaired eGFRpredischarge (<60 ml/min/1.73 m2 ) had more 4P-MACE than those with preserved eGFRpredischarge (64.7% vs. 43.1%, p = .019). The Kaplan-Meier survival curves showed significantly higher incidence of 4P-MACE in patients with impaired eGFRpredischarge than those with preserved eGFRpredischarge (p = .002). Cox regression analysis revealed that impaired eGFRpredischarge was significantly correlated with the development of 4P-MACE (hazard ratio, 2.003; 95% confidence interval, 1.072-3.744; p = .029). In contrast, outcomes would be similar with regard to eGFR on admission and eGFR decline during hospitalization. CONCLUSIONS Impaired renal function before discharge, but not impaired renal function on admission or WRF, is a significant risk factor for poor outcomes in patients with ADHF.
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5.
Intraoperative Enteral Nutrition Feeding in Free-Flap Healing after Reconstruction Surgery for Head and Neck Cancers.
Hwang, TZ, Wang, YM, Jeng, SF, Lee, YC, Chen, TS, Su, SY, Huang, CC, Lam, CF
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2023;(4):843-851
Abstract
OBJECTIVE To investigate the beneficial outcomes of intraoperative enteral feeding in free-flap regeneration after extended head and neck cancer resection and flap reconstruction surgery. STUDY DESIGN A pilot randomized, double-blind, placebo-controlled clinical trial. SETTING Single tertiary care center. METHODS Patients with advanced head and neck cancers requiring radical tumor resections and free-flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mL at 10-20 mL/h) via a nasogastric tube during free-flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free-flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90-day follow-up ended in April 2022. RESULTS The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9-43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)-6 and IL-8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups. CONCLUSION Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations.
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6.
Impact of kidney size on the outcome of diabetic patients receiving hemodialysis.
Wang, M, Hsu, HC, Yu, MC, Wang, IK, Huang, CC, Chan, MJ, Weng, CH, Huang, WH, Hsu, CW, Huang, LM, et al
PloS one. 2022;(3):e0266231
Abstract
INTRODUCTION Diabetic patients normally have enlarged or normal-sized kidneys throughout their lifetime, but some diabetic uremic patients have small kidneys. It is uncertain if kidney size could have any negative impact on outcome in hemodialysis patients. METHODS This longitudinal, observational cohort study recruited 301 diabetic hemodialysis patients in 2015, and followed until 2019. Patients were stratified into two subgroups according to their kidney sizes before dialysis, as small (n = 32) or enlarged or normal (n = 269). Baseline demographic, hematological, biochemical, nutritional, inflammatory and dialysis related data were collected for analysis. RESULTS Patients with small kidney size were not only older (P<0.001) and had lower body mass index (P = 0.016), but had also higher blood uric acid concentration (P<0.001) compared with patients with enlarged or normal kidney size. All patients received adequate doses of hemodialysis since the Kt/V and urea reduction ratio was 1.7±0.3 and 0.7±0.1, respectively. Patients with small size kidneys received higher erythropoietin dose than patients with enlarged or normal kidney size (P = 0.031). At the end of analysis, 92 (30.6%) patients expired. Kaplan-Meier analysis revealed no survival difference between both groups (P = 0.753). In a multivariate logistic regression model, it was demonstrated that age (P<0.001), dialysis duration (P<0.001), as well as blood albumin (P = 0.012) and low-density lipoprotein (P = 0.009) concentrations were significantly correlated with mortality. CONCLUSIONS Small kidney size on starting hemodialysis was not related with an augmented risk for death in diabetic patients receiving hemodialysis. Further studies are necessary.
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7.
Pleiotropic effect of sodium-glucose cotransporter 2 inhibitors on blood pressure.
Kao, TW, Huang, CC
Frontiers in cardiovascular medicine. 2022;:1086672
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been incorporated as guideline-directed medical therapy for heart failure with reduced ejection fraction. Recent trials clearly established the efficacy of SGLT2 inhibitors on cardiac remodeling while preventing renal function decline in patients with or without diabetes mellitus. Blood pressure reduction during SGLT2 inhibitors use has been proposed through pleiotropic pathways and as a potential contributor that translates to cardiovascular benefits. The mechanisms underlying this decrease in blood pressure are not simply glycemic control. Orchestrating fluid status, modulation of sodium content and renin-angiotensin-activation system, anti-fibrosis and anti-inflammatory effect, ameliorating the characteristics of metabolic syndrome, as well as restoration of circadian rhythm all contributed to the BP lowering effect by SGLT2 inhibitors. Although SGLT2 inhibitors has not been demonstrated as anti-hypertensive agents thus far, their effects on BP alteration are clinically significant. In this review, we revisited the evidence correlating SGLT2 inhibitor use with blood pressure level. Future research directions will focus on the signaling pathway of SGLT2 inhibitors for fluid removal, atherosclerosis, vasoconstriction, and eventually hypertension.
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8.
The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis.
Yin, WW, Huang, CC, Chen, YR, Yu, DQ, Jin, M, Feng, C
BMC endocrine disorders. 2022;(1):158
Abstract
OBJECTIVE The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). METHODS Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. RESULTS After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). CONCLUSIONS Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.
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9.
KDM2A plays a dual role in regulating the expression of malignancy-related genes in esophageal squamous cell carcinoma.
Wang, J, Zhang, ZY, Jiang, J, Tang, L, Wang, XY, Wang, Z, Yang, XL, Yu, XL, Huang, CC, Chen, F, et al
Biochemical and biophysical research communications. 2022;:53-58
Abstract
KDM2A is a histone demethylase, which primarily catalyzes the demethylation of H3K36me2. Abnormal expression of KDM2A is observed in many types of cancers; however, the molecular events connected to KDM2A expression remain unclear. We report that KDM2A performs an oncogenic function in esophageal squamous cell carcinoma (ESCC) and is robustly expressed in ESCC cells. ShRNA-mediated knockdown of KDM2A resulted in a significant inhibition of the malignant phenotype of ESCC cell lines, whereas ectopic expression of KDM2A showed the opposite effect. We also analyzed the function of KDM2A using a CRISPR-CAS9 depletion system and subsequent rescue experiment, which also indicated a cancerous role of KDM2A. Interestingly, analysis of the gene expression network controlled by KDM2A using RNA-seq revealed an unexpected feature: KDM2A could induce expression of a set of well-documented oncogenic genes, including IL6 and LAT2, while simultaneously suppressing another set of oncogenes, including MAT2A and HMGCS1. Targeted inhibition of the upregulated oncogene in the KDM2A-depleted cells led to a synergistic suppressive effect on the malignant phenotype of ESCC cells. Our results revealed the dual role of KDM2A in ESCC cells, which may have therapeutic implications.
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10.
Live and Heat-Killed Probiotic Lactobacillus paracasei PS23 Accelerated the Improvement and Recovery of Strength and Damage Biomarkers after Exercise-Induced Muscle Damage.
Lee, MC, Ho, CS, Hsu, YJ, Huang, CC
Nutrients. 2022;(21)
Abstract
Excessive, high-intensity or inappropriate exercise may cause muscle damage. How to speed up recovery and reduce exercise discomfort are currently very important issues for athletes and sports people. Past research has shown that probiotics can improve inflammation and oxidative stress, as well as improve exercise performance and antifatigue. However, further research is needed to confirm the recovery benefits for muscle damage. In this double-blind design study, all subjects were randomly assigned to placebo, a live Lactobacillus paracasei group (L-PS23, 2 × 1010 colony forming unit (CFU)/day), or a heat-killed L. paracasei group (HK-PS23, 2 × 1010 cells/day), and supplemented for six consecutive weeks. Afterwards, subjects completed 100 maximal vertical jumps to bring about exercise-induced muscle damage (EIMD). Countermovement jump (CMJ), isometric mid-thigh pull (IMTP), and Wingate anaerobic test (WAnT), as well as blood tests for markers of muscle damage and inflammation were made pre-exercise and 3, 24, 48 h post exercise. The results show that both L-PS23 and HK-PS23 supplementation significantly slowed the loss of muscle strength after muscle injury, and they significantly reduced the production of markers of muscle damage and inflammation (p < 0.05). In addition, L-PS23 and HK-PS23 had the benefits of accelerating the recovery and improvement of muscle strength, the blood markers of muscle injury and inflammation, and slowing the decline in testosterone concentrations (p < 0.05). Especially in the HK-PS23 supplemented group, there was a better trend. In conclusion, we found that L-PS23 or HK-PS23 supplementation for six weeks prevented strength loss after muscle damage and improved blood muscle damage and inflammatory markers, with protective, accelerated recovery and anti-fatigue benefits.