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1.
J Med Virol ; 96(5): e29675, 2024 May.
Article En | MEDLINE | ID: mdl-38746997

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.


Antiviral Agents , Hepacivirus , Hepatitis C, Chronic , RNA, Viral , Sustained Virologic Response , Humans , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Male , Female , Middle Aged , Hepacivirus/genetics , Hepacivirus/drug effects , Aged , Adult , RNA, Viral/blood , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Recurrence , Follow-Up Studies , Treatment Outcome , Hepatitis C/drug therapy , Hepatitis C/virology
2.
J Fungi (Basel) ; 10(4)2024 Mar 30.
Article En | MEDLINE | ID: mdl-38667933

Microbotryum lychnidis-dioicae is an obligate fungal species colonizing the plant host, Silene latifolia. The fungus synthesizes and secretes effector proteins into the plant host during infection to manipulate the host for completion of the fungal lifecycle. The goal of this study was to continue functional characterization of such M. lychnidis-dioicae effectors. Here, we identified three putative effectors and their putative host-plant target proteins. MVLG_02245 is highly upregulated in M. lychnidis-dioicae during infection; yeast two-hybrid analysis suggests it targets a tubulin α-1 chain protein ortholog in the host, Silene latifolia. A potential plant protein interacting with MVLG_06175 was identified as CASP-like protein 2C1 (CASPL2C1), which facilitates the polymerization of the Casparian strip at the endodermal cells. Proteins interacting with MVLG_05122 were identified as CSN5a or 5b, involved in protein turnover. Fluorescently labelled MVLG_06175 and MVLG_05122 were expressed in the heterologous plant, Arabidopsis thaliana. MVLG_06175 formed clustered granules at the tips of trichomes on leaves and in root caps, while MVLG_05122 formed a band structure at the base of leaf trichomes. Plants expressing MVLG_05122 alone were more resistant to infection with Fusarium oxysporum. These results indicate that the fungus might affect the formation of the Casparian strip in the roots and the development of trichomes during infection as well as alter plant innate immunity.

3.
J Gastroenterol ; 2024 Apr 13.
Article En | MEDLINE | ID: mdl-38613690

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

4.
J Agric Food Chem ; 72(12): 6339-6346, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38488910

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.


Chlorogenic Acid/analogs & derivatives , Diabetes Mellitus, Type 2 , Morus , Non-alcoholic Fatty Liver Disease , Quinic Acid/analogs & derivatives , Mice , Animals , Catalase/metabolism , Morus/metabolism , Antioxidants/metabolism , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Glutathione/metabolism , Superoxide Dismutase/metabolism , Lipids/pharmacology , Plant Leaves/metabolism , Mice, Inbred C57BL
5.
Cancers (Basel) ; 16(5)2024 Feb 28.
Article En | MEDLINE | ID: mdl-38473337

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

6.
Article En | MEDLINE | ID: mdl-38388021

BACKGROUND AND AIM: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated. METHODS: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology. RESULTS: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy. CONCLUSIONS: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions.

7.
Clin Mol Hepatol ; 30(1): 64-79, 2024 Jan.
Article En | MEDLINE | ID: mdl-38195113

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.


Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Humans , Hepacivirus/genetics , Artificial Intelligence , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , RNA
8.
Hepatol Int ; 18(2): 461-475, 2024 Apr.
Article En | MEDLINE | ID: mdl-38246899

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.


Aminoisobutyric Acids , Benzimidazoles , Benzopyrans , Carbamates , Cyclopropanes , Hepatitis C, Chronic , Hepatitis C , Heterocyclic Compounds, 4 or More Rings , Lactams, Macrocyclic , Leucine/analogs & derivatives , Liver Neoplasms , Proline/analogs & derivatives , Sulfonamides , Humans , Aged , Sofosbuvir/therapeutic use , Sofosbuvir/pharmacology , Antiviral Agents , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Taiwan/epidemiology , Quinoxalines/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/complications , Liver Neoplasms/drug therapy , Bilirubin , Genotype
9.
J Formos Med Assoc ; 2024 Jan 02.
Article En | MEDLINE | ID: mdl-38171957

BACKGROUND/PURPOSE: Endoscopic stenting at malignant distal duodenum stenosis (MDDS) is challenging because of the duodenal C-loop configuration, the acute angle of the duodenojejunal junction, and the limited length of the endoscope. Few studies have investigated the clinical outcomes of stenting at the distal duodenum. Therefore, this study aimed to investigate the clinical outcomes of treating MDDS with different types of metallic stents. METHODS: From January 2012 to December 2020, fifty-six patients with MDDS who underwent duodenal stenting were enrolled for analysis. Thirty-five patients received uncovered self-expandable metallic stents (UC-SEMS), and twenty-one patients received partially covered self-expandable metallic stents (PC-SEMS). All patients were followed up till death or for 18 months. The clinical success rate, stent dysfunction rate, and stent patency were compared between the groups. Multivariate analysis was conducted to identify factors related to stent dysfunction. RESULTS: The clinical success rates were 85.7 % in both the UC-SEMS and PC-SEMS groups. Stent dysfunction rates (UC-SEMS: 34.3 %, PC-SEMS: 38.1 %, p = 0.773) and the average stent patency (UC-SEMS: 117.2 days, PC-SEMS: 100.0 days, p = 0.576) were not statistically different between the groups. Multivariate analysis disclosed the age ≥65 years was significantly related to stent dysfunction (odds ratio: 4.78, p = 0.031). CONCLUSIONS: Both UC-SEMS and PC-SEMS are safe and effective treatment options for MDDS. However, stent dysfunction remains a significant issue to overcome, particularly in the elderly. Further research is needed to explore novel strategies that can improve the effectiveness of stent placement and reduce the risk of stent dysfunction.

10.
Environ Toxicol ; 39(4): 2077-2085, 2024 Apr.
Article En | MEDLINE | ID: mdl-38100242

Colorectal cancer (CRC) exhibits highly metastatic potential even in the early stages of tumor progression. Gallic acid (GA), a common phenolic compound in plants, is known to possess potent antioxidant and anticancer activities, thereby inducing cell death or cell cycle arrest. However, whether GA reduces the invasiveness of CRC cells without inducing cell death remains unclear. Herein, we aimed to investigate the antimetastatic activity of low-dose GA on CRC cells and determine its underlying mechanism. Cell viability and tumorigenicity were analyzed by MTS, cell adhesion, and colony formation assay. Invasiveness was demonstrated using migration and invasion assays. Changes in protein phosphorylation and expression were assessed by Western blot. The involvement of microRNAs was validated by microarray analysis and anti-miR antagonist. Our findings showed that lower dose of GA (≤100 µM) did not affect cell viability but reduced the capabilities of colony formation, cell adhesion, and invasiveness in CRC cells. Cellularly, GA downregulated the cellular level of integrin αV/ß3, talin-1, and tensin and diminished the phosphorylated FAK, paxillin, Src, and AKT in DLD-1 cells. Microarray results revealed that GA increased miR-1247-3p expression, and pretreatment of anti-miR antagonist against miR-1247-3p restored the GA-reduced integrin αV/ß3 and the GA-inhibited paxillin activation in DLD-1 cells. Consistently, the in vivo xenograft model showed that GA administration inhibited tumor growth and liver metastasis derived from DLD-1 cells. Collectively, our findings indicated that GA inhibited the metastatic capabilities of CRC cells, which may result from the suppression of integrin/FAK axis mediated by miR1247-3p.


Colorectal Neoplasms , MicroRNAs , Humans , Paxillin/genetics , Paxillin/metabolism , Integrins/genetics , Integrins/metabolism , Gallic Acid/pharmacology , Antagomirs , Integrin alphaV/metabolism , Cell Line, Tumor , Cell Proliferation , MicroRNAs/genetics , MicroRNAs/metabolism , Colorectal Neoplasms/metabolism , Cell Movement , Gene Expression Regulation, Neoplastic
11.
Sensors (Basel) ; 23(17)2023 Aug 25.
Article En | MEDLINE | ID: mdl-37687878

Wheelchair sports have been using Inertial Measurement Units (IMU) to measure mobility metrics during training, testing and competition. Presently, the most suitable solution to calculate wheelchair speed and frame rotation is the 3IMU method as there is uncertainty about the ability of a one wheel-mounted IMU (1IMU) approach to calculate wheelchair frame rotational kinematics. A new method for calculating wheelchair frame rotational kinematics using a single wheel-mounted IMU is presented and compared to a criterion measurement using a wheelchair-frame-mounted IMU. Goodness-of-fit statistics demonstrate very strong linear relationships between wheelchair frame angular velocity calculated from the wheel-mounted IMUs and a wheelchair-frame-mounted IMU. Root mean square error (RMSE), mean absolute error (MAE) and Bland-Altman analysis show very small differences between the wheelchair frame angular velocity calculated from the wheel-mounted IMUs and the wheelchair-frame-mounted IMU. This study has demonstrated a simple and accurate approach to estimating wheelchair frame rotation using one wheel-mounted IMU during an elite wheelchair athlete agility task. Future research is needed to reexamine and compare wheelchair mobility metrics determined using the 3IMU and 1IMU solutions using this new approach.


Benchmarking , Wheelchairs , Humans , Rotation
12.
Sensors (Basel) ; 23(17)2023 Aug 29.
Article En | MEDLINE | ID: mdl-37687947

BACKGROUND: Para-sports such as wheelchair rugby have seen increased use of inertial measurement units (IMU) to measure wheelchair mobility. The accessibility and accuracy of IMUs have enabled the quantification of many wheelchair metrics and the ability to further advance analyses such as force-velocity (FV) profiling. However, the FV modeling approach has not been refined to include wheelchair specific parameters. PURPOSE: The purpose of this study was to compare wheelchair rugby sprint FV profiles, developed from a wheel-mounted IMU, using current mono-exponential modeling techniques against a dynamic resistive force model with wheelchair specific resistance coefficients. METHODS: Eighteen athletes from a national wheelchair rugby program performed 2 × 45 m all-out sprints on an indoor hardwood court surface. RESULTS: Velocity modelling displayed high agreeability, with an average RMSE of 0.235 ± 0.07 m/s-1 and r2 of 0.946 ± 0.02. Further, the wheelchair specific resistive force model resulted in greater force and power outcomes, better aligning with previously collected measures. CONCLUSIONS: The present study highlights the proof of concept that a wheel-mounted IMU combined with wheelchair-specific FV modelling provided estimates of force and power that better account for the resistive forces encountered by wheelchair rugby athletes.


Sports , Wheelchairs , Humans , Rugby , Athletes , Benchmarking
13.
Int J Sports Physiol Perform ; 18(12): 1427-1434, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37739401

PURPOSE: Ice hockey is a team invasion sport characterized by repeated high-intensity skating efforts, technical and tactical skill, physical contact, and collisions requiring considerable levels of muscular strength. The purpose of this study was to evaluate the relationships between lower-body vertical force-time metrics and skating qualities in subelite female ice hockey players. METHODS: A cross-sectional cohort design was employed utilizing 14 athletes (body mass = 66.7 [1.8] kg; height = 171.6 [6.2] cm; age = 21.1 [1.7] y). The relationships between metrics of lower-body strength collected from a drop jump, squat jump, countermovement jump, loaded countermovement jump, and an isometric squat and 4 skating qualities collected from a linear sprint, repeated sprint test, and a multistage aerobic test were evaluated. RESULTS: The regression models revealed a positive relationship between relative peak force in the isometric squat and skating multistage aerobic test performance (r2 = .388; P = .017) and a positive relationship between repeated-sprint ability and eccentric mean force during the loaded countermovement jump (r2 = .595; P = .001). No significant relationships were observed between strength metrics and skating acceleration or maximal velocity. CONCLUSIONS: These data suggest that skating ability is most affected by relative isometric strength in female ice hockey players. It is recommended that practitioners focus training on tasks that improve relative force output. It is also recommended that isometric relative peak force be used as a monitoring metric for this cohort.


Athletic Performance , Hockey , Skating , Humans , Female , Young Adult , Adult , Cross-Sectional Studies , Muscle Strength
14.
Medicina (Kaunas) ; 59(9)2023 Aug 24.
Article En | MEDLINE | ID: mdl-37763649

Background and Objectives: PNU-74654, a Wnt/ß-catenin pathway inhibitor, has an antiproliferative effect on many cancer types; however, its therapeutic role in pancreatic cancer (PC) has not yet been demonstrated. Here, the effects of PNU-74654 on proliferation and cell cycle phase distribution were studied in PC cell lines. Materials and Methods: The cancer-related molecular pathways regulated by PNU-74654 were determined by a proteome profiling oncology array and confirmed by western blotting. Results: The cell viability and proliferative ability of PC cells were decreased by PNU-74654 treatment. G1 arrest was observed, as indicated by the downregulation of cyclin E and cyclin-dependent kinase 2 (CDK2) and the upregulation of p27. PNU-74654 inhibited the epithelial-mesenchymal transition (EMT), as determined by an increase in E-cadherin and decreases in N-cadherin, ZEB1, and hypoxia-inducible factor-1 alpha (HIF-1α). PNU-74654 also suppressed cytoplasmic and nuclear ß-catenin and impaired the NF-κB pathway. Conclusions: These results demonstrate that PNU-74654 modulates G1/S regulatory proteins and inhibits the EMT, thereby suppressing PC cell proliferation, migration, and invasion. The synergistic effect of PNU-74654 and chemotherapy or the exclusive use of PNU-74654 may be therapeutic options for PC and require further investigation.


Pancreatic Neoplasms , beta Catenin , Humans , beta Catenin/metabolism , Epithelial-Mesenchymal Transition , Cell Movement , Cell Cycle Checkpoints , Cell Proliferation , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , Cell Line, Tumor
15.
Nutrients ; 15(18)2023 Sep 14.
Article En | MEDLINE | ID: mdl-37764756

Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, have potential anticancer properties. Our study investigated the in vitro cytotoxic potential and mode of action of HAs extracts containing anthocyanins in colorectal cancer cells. The results showed that Hibiscus anthocyanin-rich extracts induced apoptosis in human colorectal cancer cells through the activation of multiple signaling pathways of AMPK. We observed the dose-response and time-dependent induction of apoptosis with HAs. Subsequently, the activation of Fas-mediated proteins triggered apoptotic pathways associated with Fas-mediated apoptosis-related proteins, including caspase-8/tBid. This caused the release of cytochrome C from the mitochondria, resulting in caspase-3 cleavage and apoptosis activation in intestinal cancer cells. These data elucidate the relationship between Has' regulation of apoptosis-related proteins in colorectal cancer cells and apoptotic pathways.

16.
Int J Sports Physiol Perform ; 18(12): 1457-1460, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37741637

PURPOSE: To determine the minimum number of events (training or matches) for producing valid acceleration-speed (AS) profiles from global navigation satellite system (GNSS) data. METHODS: Nine elite female soccer players participated in a 4-week training camp consisting of 19 events. AS profile metrics calculated from different combinations of athlete events were compared to force-velocity (FV) profile metrics from 2 × 40-m stand-alone sprint effort trials, using the same GNSS 10-Hz technology. Force-velocity profiles were calculated, from which AS profiles were obtained. AS profiles from training and matches were generated by plotting acceleration and speed points and performing a regression through the maximal points to obtain the AS metrics (theoretical maximal speed, x-intercept [in meters per second], theoretical maximal acceleration, y-intercept [in meters per second squared], and the slope per second). A linear mixed model was performed with the AS metrics as the outcome variables, the number of events as a fixed effect, and the participant identifier as a mixed effect. Dunnett post hoc multiple comparisons were used to compare the means of each number of event grouping (1-19 events) to those estimated from the dedicated sprint test. RESULTS: Theoretical maximal speed and theoretical maximal acceleration means were no longer significantly different from the isolated sprint reference with 9 to 19 (small to trivial differences = -0.31 to -0.04 m·s-1, P = .12-.99) and 6 to 19 (small differences = -0.4 to -0.28 m·s-2, P = .06-.79) events, and the slopes were no longer different with 1 to 19 events (trivial differences = 0.06-0.03 s-1, P = .35-.99). CONCLUSIONS: AS profiles can be estimated from a minimum of 9 days of tracking data. Future research should investigate methodology resulting in AS profiles estimated from fewer events.


Athletic Performance , Running , Soccer , Humans , Female , Acceleration
17.
Nutrients ; 15(16)2023 Aug 08.
Article En | MEDLINE | ID: mdl-37630688

Non-alcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver. It spans a spectrum of diseases from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Brassica juncea is rich in glucosinolates and has been proven to possess many potential pharmacological properties, including hypoglycemic, anti-oxidation, anti-inflammatory, and anti-carcinogenic activities. This study aims to investigate whether whole-plant Brassica juncea (WBJ) and its glucosinolates extracts (BGE) have hepatoprotective effects against a high-fat diet (HFD)-induced NAFLD and further explore the mechanism underlying this process in vivo and in vitro. WBJ treatment significantly reduced body fat, dyslipidemia, hepatic steatosis, liver injury, and inflammation; WBJ treatment also reversed the antioxidant enzyme activity to attenuate oxidative stress in HFD-fed rat liver. Moreover, WBJ and BGE enhanced the activation of AMPK to reduce SREBPs, fatty acid synthase, and HMG-CoA reductase but increased the expression of CPT-I and PPARα to improve hepatic steatosis. In addition, WBJ and BGE could ameliorate NAFLD by inhibiting TNF-α and NF-κB. Based on the above results, this study demonstrates that WBJ and BGE ameliorate HFD-induced hepatic steatosis and liver injury. Therefore, these treatments could represent an unprecedented hope toward improved strategies for NAFLD.


Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Animals , Rats , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Glucosinolates/pharmacology , Mustard Plant , Diet, High-Fat/adverse effects , Antioxidants/pharmacology , Plant Extracts/pharmacology
18.
J Biomech ; 157: 111724, 2023 08.
Article En | MEDLINE | ID: mdl-37451206

This study aimed to (1) compare "in-situ" monitored acceleration-speed (ASin-situ) profile metrics from training/competition data in elite female soccer players to similar metrics from profiles developed from isolated maximal sprint efforts (ASsprint) and; (2) compare the confidence interval (CI) and a Tukey boxplot (BP) outlier removal technique on the training/competition data to derive ASin-situ profiles. Fifteen national team soccer players participated in a 4-week camp while wearing 10 Hz GNSS units. Towards the middle of the camp, 2 × 40 m isolated maximal sprints were performed. ASin-situ profiles (theoretical maximum acceleration A0 in m∙s-2 and speed S0 in m∙s-1) were computed using the CI and BP techniques with training/competition data. The sprint data were modelled separately to construct horizontal force-velocity (FV) profiles, from which ASsprint profiles were derived. Bland-Altman analysis was used to assess agreement between the CI- and BP-derived ASin-situ profiles to the ASsprint profiles, as well as regression analysis for systematic and proportional bias. Additionally, 1-way ANOVAs with Tukey posthoc compared the metrics between each method of analysis. Using the BP method, good agreement of the ASin-situ with ASsprint profile metrics A0/S0 was displayed, whereas good to moderate agreement was shown for the CI. The CI technique showed a proportional bias for A0/S0. Good to excellent intertrial reliability was demonstrated for isolated sprint metrics. Both BP and CI techniques provided comparable ASin-situ profiles to ASsprint profiles. This current research demonstrated that ASin-situ profiling is applicable in elite women's soccer and will have further application in many team sports.


Athletic Performance , Running , Soccer , Humans , Female , Reproducibility of Results , Acceleration
19.
J Strength Cond Res ; 37(6): 1298-1305, 2023 Jun 01.
Article En | MEDLINE | ID: mdl-36727987

ABSTRACT: Cormier, P, Tsai, M-C, Meylan, C, Agar-Newman, D, Epp-Stobbe, A, Kalthoff, Z, and Klimstra, M. Concurrent validity and reliability of different technologies for sprint-derived horizontal force-velocity-power profiling. J Strength Cond Res 37(6): 1298-1305, 2023-This study evaluated the validity and reliability of common systems to assess sprint-derived horizontal force-velocity-power ( FVPH ) profile metrics. Two double constellation athlete monitoring systems (STATSports Apex, Catapult Vector S7) and one timing gate system were compared with a radar gun for the computation of FVPH metrics. Intersystem validity was assessed using intraclass correlation coefficients (ICC), Pearson's correlation coefficients ( R2 ), and Bland-Altman plots with absolute and percent agreement. Intrasystem reliability was assessed with agreement bias and ICC. STATSports demonstrated moderate agreement for F0 , Pmax , τ, and Drf (8.62, 6.46, -9.81, and 9.96%, respectively) and good agreement for V0 and MSS (-2.18 and -1.62%). Catapult displayed good agreement across all metrics ( F0 , V0 , Pmax , MSS, τ, and Drf : -0.96, -0.89, -1.85, -0.84, 0.38, and -0.27%, respectively). Timing gates demonstrated good agreement with V0 and MSS (-2.62 and -1.71%) and poor agreement with F0 , Pmax , τ, and Drf (19.17, 16.64, -20.49, and 20.18%, respectively). Intrasystem reliability demonstrated good agreement (<2% bias) with very large to near-perfect ICC (0.84-0.99) for Catapult and STATSports systems. Overall, GPS/GNSS 10 Hz technology is reliable across devices and can provide moderate-to-good accuracy of FVPH metrics in single maximal effort sprints. However, Catapult provided better agreement for more FVPH metrics than STATSports, which may be related to differences in proprietary algorithms. Also, modeling timing gate data using current FVPH profiling techniques results in poor bias that requires greater investigation. GPS/GNSS data can be used for FVPH profiling, which could inform performance and rehabilitation processes.


Athletic Performance , Running , Humans , Reproducibility of Results , Athletes , Radar
20.
Healthcare (Basel) ; 11(2)2023 Jan 04.
Article En | MEDLINE | ID: mdl-36673528

Primary liver cancer is one of the leading causes of death globally. Liver cancer has a unique geographical distribution, as its etiologies include chronic viral infections and aging. We hypothesize that the human development index (HDI), current health expenditure (CHE) per capita, and CHE-to-gross domestic product ratio (CHE/GDP) influence the incidence, mortality, and mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data were obtained from the Global Cancer Observatory (GLOBOCAN) database and the World Health Organization. MIRs and the changes in MIR over time (δMIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The crude incidence and mortality were significantly associated with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between δMIR and HDI, as well as between δMIR and CHE per capita. However, there were no significant associations between δMIR and CHE/GDP. Evidently, a favorable liver cancer δMIR was not associated with CHE/GDP, although it had a significant association with HDI and CHE per capita. These results are worthy of the attention of public health systems in correlation to improved outcomes in liver cancer.

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