Salvinal is a natural lignan isolated from the roots of
Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, ...with IC
values ranging from 4-17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure-activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound
displayed excellent anticancer activity, with IC
values of 0.13-0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound
showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound
is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.
Metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disease characterized by an abnormal buildup of fat in liver. ...This study aimed to investigate whether bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet (HFFD)-induced MAFLD in C57BL/6J mice. Sixty male C57BL/6J mice were randomly divided into six groups. The naïve group (untreated) was fed a standard chow diet and other groups were fed with HFFD along with vehicle and bioactive dipeptides treatment throughout experiment period. The control group received vehicle, YF10 and YF50 groups received Tyr-Phe, 10 and 50 mg/kg/day, FY10 and FY50 groups received Phe-Tyr, 10 and 50 mg/kg/day. At the end of experiment, body weight was recorded, and glucose homeostasis was assessed. Mice were sacrificed and blood samples were collected to measure biochemical parameters. Further, liver, visceral fat pads, and other organs were acutely dissected, weighed, and processed. Histopathological and immunohistochemical changes were analyzed. Long-term HFFD feeding resulted in elevated body weight gain, liver weight, visceral adiposity, liver injury, fasting hyperglycemia, hyperinsulinemia, and hyperlipidemia. It also increased severe hepatic steatosis, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and lipid peroxidation. However, bioactive dipeptides dose-dependently alleviated these complications which are associated with MAFLD by modulating adipokines secretion and antioxidant defense system via upregulation of Nrf2/HO-1 expressions. This study highlights potential of bioactive dipeptides as a promising approach for prevention and/or treatment of MAFLD induced by HFFD, providing novel insights into alternative therapeutic strategies.
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•Bioactive dipeptides markedly reduced aberrant visceral adiposity and weight gain.•Bioactive dipeptides improved glucose tolerance and insulin sensitivity.•Bioactive dipeptides modulate adipokine secretion.•Bioactive dipeptides upregulate antioxidant defense via Nrf2/HO-1 signaling.•Novel approach for prevention and/or treatment of diet-induced MAFLD.
Transcription factors (TFs) are sequence-specific DNA-binding proteins acting as critical regulators of gene expression. The Plant Promoter Analysis Navigator (PlantPAN; ...http://PlantPAN2.itps.ncku.edu.tw) provides an informative resource for detecting transcription factor binding sites (TFBSs), corresponding TFs, and other important regulatory elements (CpG islands and tandem repeats) in a promoter or a set of plant promoters. Additionally, TFBSs, CpG islands, and tandem repeats in the conserve regions between similar gene promoters are also identified. The current PlantPAN release (version 2.0) contains 16 960 TFs and 1143 TF binding site matrices among 76 plant species. In addition to updating of the annotation information, adding experimentally verified TF matrices, and making improvements in the visualization of transcriptional regulatory networks, several new features and functions are incorporated. These features include: (i) comprehensive curation of TF information (response conditions, target genes, and sequence logos of binding motifs, etc.), (ii) co-expression profiles of TFs and their target genes under various conditions, (iii) protein-protein interactions among TFs and their co-factors, (iv) TF-target networks, and (v) downstream promoter elements. Furthermore, a dynamic transcriptional regulatory network under various conditions is provided in PlantPAN 2.0. The PlantPAN 2.0 is a systematic platform for plant promoter analysis and reconstructing transcriptional regulatory networks.
Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. ...Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 10
, 4.10 × 10
and 1.03 × 10
CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.
Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and ...severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.
191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR
) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed.
The SVR
rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR
rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR
rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR
were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations.
SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.
Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product ...with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg,
< 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm
, db/db: 6538.5 ± 1818.6 μm
, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm
, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm
< 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial-mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.
Abstract
Clinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, ...glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.
Probiotics are increasingly being used as a nutritional supplement by athletes to improve exercise performance and reduce post-exercise fatigue.
is a natural flora in the gastrointestinal tract of ...humans and animals.
subspecies
(SA-03) is an isolate from the 2008 Olympic women's 48 kg weightlifting gold medalist's gut microbiota. In this study, we investigated its beneficial effects on physical fitness. Male ICR mice were divided into four groups (
= 10 per group) and orally administered with SA-03 for 4 weeks at 0, 2.05 × 10
, 4.10 × 10
, or 1.03 × 10
CFU/kg/day. Results showed that 4 weeks of SA-03 supplementation significantly improved muscle strength and endurance performance, increased hepatic and muscular glycogen storage, and decreased lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise. These observations suggest that SA-03 could be used as a nutritional supplement to enhance exercise performance and reduce.
Due to the internal environment of highway tunnels, tunnel lighting has scattering, deflection, illuminance, and uniformity problems. Each factor will have a direct impact on drivers. Due to the low ...illuminance and brightness, the lighting efficiency can be improved by shortening the diodes’ distance. The SmileRay LED street light module will be adopted as the primary design structure, and the CREO modeling software will construct the initial lens model. The geometric optics laws will be applied, the LightTools will be used to simulate the second optical lens design, lightbar light source module design, lighting mechanism modifications, etc., and then use the lens light distribution with the DIALux lighting design software to carry out the tunnel lighting simulation of spec verification, and optimize the installation through the results. The simulation results show the tunnel lighting module designed in this research can provide 10499 lm of luminous flux when the lamp energy consumption is only 75 W. The total lamp optical efficiency reaches 97%, and the brightness uniformity comes to 0.755 after the modified installation, which aligns with the CIE 88–2004 tunnel lighting specification standard.
A tailor-made medium-band gap fluorinated quinoxaline-based conjugated polymer of PBDT-TFQ was designed and synthesized as a donor material for bulk-heterojunction (BHJ) solar cells. This polymer is ...possessed of an intrachain donor–acceptor architecture and exhibits a broad and strong absorption spectrum across the entire UV–vis region. The introduction of F atoms with high electron affinity to the quinoxaline moiety is effective in further lowering both the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of PBDT-TFQ to attain higher open-circuit voltage (V oc). With an optimized blend ratio of PBDT-TFQ:PC71BM (1:1, w/w), a high power conversion efficiency (PCE) of 8.0% was obtained, with a V oc of 0.76 V, a short-circuit current density (J sc) of 18.2 mA cm–2, and a fill factor (FF) of 58.1% under AM 1.5G irradiation. The resulting copolymer reveals an outstanding J sc value, arising from the higher hole mobility of PBDT-TFQ, together with the better continuous percolation pathways within the polymer blend for efficient exciton dissociation and charge transport.
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