| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Thomas, M, et al.
(författare)
-
Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity
- 2023
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values<0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
|
|
| 9. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 10. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Gong, XZ, et al.
(författare)
-
Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats
- 2016
-
Ingår i: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2016, s. 8715185-
-
Tidskriftsartikel (refereegranskat)abstract
- Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI) due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA); the amide form of N-acetyl cysteine (NAC) prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1) and apoptosis signal-regulating kinase 1 (ASK1) act as the potential activator for p38 MAPK. NACA significantly attenuated elevations of serum creatinine, blood urea nitrogen, and biomarkers of AKI. At equimolar concentration, NACA was more effective than NAC in reducing histological changes of renal tubular injuries. NACA attenuated activation of p38 MAPK signal, reduced oxidative stress, and diminished apoptosis. Furthermore, we demonstrated that contrast exposure resulted in Trx1 downregulation and increased ASK1/p38 MAPK phosphorylation, which could be reversed by NACA and NAC. To our knowledge, this is the first report that Trx1 and ASK1 are involved in CIN. Our study highlights a renal protective role of NACA against CIN through modulating Trx1 and ASK1/p38 MAPK pathway to result in the inhibition of apoptosis among renal cells.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Li, XB, et al.
(författare)
-
Novel TCF21high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix
- 2023
-
Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 72:4, s. 710-721
-
Tidskriftsartikel (refereegranskat)abstract
- Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.DesignTPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 onTCF21DNA hypermethylation. Pericyte-conditionalTcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling.ResultsThirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21highTPCs, termed ‘matrix–pericytes’, was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM).Tcf21depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21highTPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impairTCF21DNA hypermethylation in TCF21highTPCs.ConclusionThis study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.
|
|
| 18. |
- Peng, Y, et al.
(författare)
-
The effect of low volume high-intensity interval training on metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus: A systematic review and meta-analysis
- 2023
-
Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 1098325-
-
Tidskriftsartikel (refereegranskat)abstract
- The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effect of low volume high-intensity interval training (LVHIIT) on the metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus (T2DM).MethodsRelevant articles were sourced from PubMed, EBSCO, Web of Science, Embase, and the Cochrane Library from inception to October 2022. The study search strategy and all other processes were implemented in accordance with the PRISMA statement.ResultsFive randomized controlled trials that satisfied the inclusion criteria were included in this meta-analysis. The LVHIIT group had significantly lower fasting blood glucose levels (RR= -1.21; 95% CI= -2.02— -0.40, p = 0.0032) and HbA1c levels (RR= -0.65; 95% CI= -1.06— -0.23, p = 0.002) and higher levels of insulin resistance indicator HOMA-IR (RR= -1.34; 95% CI = -2.59— -0.10, p = 0.03) than the control group. Moreover, our results show that LVHIIT can reduce body mass (RR = -0.94, 95% CI = -1.37— -0.51, p<0.0001) and body mass index (RR = -0.31, 95% CI = -0.47— -0.16, p<0.0001). LVHIIT had a better therapeutic effect on blood lipid metabolism, such as total cholesterol, high-density lipoprotein, low-density lipoprotein and triglycerides. However, the change in fasting insulin levels was not statistically significant (RR= -1.43; 95% CI = -3.46— 0.60, p =0.17). Furthermore, LVHIIT reduced the systolic blood pressure (RR =-4.01, 95% CI = -4.82 – -3.21, p<0.0001) and improved peak oxygen uptake (VO2peak) compared to the control group (RR= 5.45; 95% CI = 1.38 – 9.52, p =0.009).ConclusionAfter a certain period of LVHIIT, glycaemic control, insulin resistance, body weight, lipid profile and cardiorespiratory outcomes were significantly improved in T2DM patients.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Zhang, JX, et al.
(författare)
-
The Efficacy and Safety of Revefenacin for the Treatment of Chronic Obstructive Pulmonary Disease: A Systematic Review
- 2021
-
Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12, s. 667027-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundRevefenacin (REV) is a novel once-daily long-acting muscarinic antagonist (LAMA) in the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). This systematic review incorporating a dose-response meta-analysis aimed to assess the efficacy and safety of REV.MethodsPubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their inception to April 2020. We included randomized controlled trials (RCTs) which evaluated the efficacy and safety of REV in COPD patients. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Outcomes consisted of the mean change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline, adverse events (AEs), and serious adverse events (SAEs). A dose-response meta-analysis using the robust error meta-regression method was conducted. We used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.ResultsNine RCTs (3,121 participants) were included in this systematic review. The meta-analyses indicated that 175 μg/day REV could significantly improve the trough FEV1(MD=143.67, 95%CI: 129.67 to 157.68; I2=96%; 809 participants; studies=4; low quality) without increasing the risk of AEs (OR=0.98, 95%CI: 0.81 to 1.18; I2=34%; 2,286 participants; studies=7; low quality) or SAEs (OR=0.89, 95%CI: 0.55 to 1.46; I2=0%; 2,318 participants; studies=7; very low quality) compared to placebo. Furthermore, the effect of REV in increasing trough FEV1was dose-dependent with an effective threshold of 88 μg/day (R2= 0.7017). Nevertheless, only very low-quality to low-quality evidence showed that REV at a dose of 175 μg/day was inferior to tiotropium regarding the long-term efficacy, and its safety profile was not superior to tiotropium or ipratropium.ConclusionCurrent evidence shows that REV is a promising option for the treatment of moderate to very severe COPD. Due to most evidence graded as low quality, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between REV and other LAMAs in different populations.Clinical Trial Registration: [PROSPERO], identifier [CRD42020182793]
|
|
| 28. |
|
|
| 29. |
- Thomas, HS, et al.
(författare)
-
- 2019
-
swepub:Mat__t
|
|
