| 1. |
|
|
| 2. |
- Mao, W, et al.
(författare)
-
Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial
- 2021
-
Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11, s. 627185-
-
Tidskriftsartikel (refereegranskat)abstract
- Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects.Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Chen, DS, et al.
(författare)
-
Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
-
Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
|
|
| 18. |
- Chen, XD, et al.
(författare)
-
Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
-
Tidskriftsartikel (refereegranskat)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Yang, YY, et al.
(författare)
-
Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring
- 2023
-
Ingår i: Environmental science and pollution research international. - : Springer Science and Business Media LLC. - 1614-7499. ; 30:4912, s. 35142-35152
-
Tidskriftsartikel (refereegranskat)abstract
- Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 μg/m3) and (2.78 ± 1.19 μg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p < 0.05), suggesting spatial memory impairments. The acquisition trials of Morris Water Maze did not show a significant difference in learning ability between the groups. The mRNA level of interleukin 6 (IL-6) in the CAP group hippocampus (10.80 ± 7.03) increased significantly compared to the FA group (1.08 ± 0.43). Interestingly, the methylation levels of the CpG sites in the IL-6 promoter region declined significantly in the CAP group, (5.66 ± 0.83)% vs. (4.79 ± 0.48)%. Prenatal exposure to concentrated ambient PM2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.
|
|
| 26. |
- Thomas, HS, et al.
(författare)
-
- 2019
-
swepub:Mat__t
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Callaway, EM, et al.
(författare)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 33. |
|
|
| 34. |
- Chi, TG, et al.
(författare)
-
PPAR-γ Modulators as Current and Potential Cancer Treatments
- 2021
-
Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 737776-
-
Tidskriftsartikel (refereegranskat)abstract
- Worldwide, cancer has become one of the leading causes of mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family of critical sensors of lipids as well as regulators of diverse metabolic pathways. They are also equipped with the capability to promote eNOS activation, regulate immunity and inflammation response. Aside from the established properties, emerging discoveries are also made in PPAR’s functions in the cancer field. All considerations are given, there exists great potential in PPAR modulators which may hold in the management of cancers. In particular, PPAR-γ, the most expressed subtype in adipose tissues with two isoforms of different tissue distribution, has been proven to be able to inhibit cell proliferation, induce cell cycle termination and apoptosis of multiple cancer cells, promote intercellular adhesion, and cripple the inflamed state of tumor microenvironment, both on transcriptional and protein level. However, despite the multi-functionalities, the safety of PPAR-γ modulators is still of clinical concern in terms of dosage, drug interactions, cancer types and stages, etc. This review aims to consolidate the functions of PPAR-γ, the current and potential applications of PPAR-γ modulators, and the challenges in applying PPAR-γ modulators to cancer treatment, in both laboratory and clinical settings. We sincerely hope to provide a comprehensive perspective on the prospect of PPAR-γ applicability in the field of cancer treatment.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Khan, RMM, et al.
(författare)
-
From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research
- 2019
-
Ingår i: Medicina (Kaunas, Lithuania). - : MDPI AG. - 1648-9144. ; 55:9
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes, a silent killer, is one of the most widely prevalent conditions of the present time. According to the 2017 International Diabetes Federation (IDF) statistics, the global prevalence of diabetes among the age group of 20–79 years is 8.8%. In addition, 1 in every 2 persons is unaware of the condition. This unawareness and ignorance lead to further complications. Pre-diabetes is the preceding condition of diabetes, and in most of the cases, this ultimately leads to the development of diabetes. Diabetes can be classified into three types, namely type 1 diabetes, type 2 diabetes mellitus (T2DM) and gestational diabetes. The diagnosis of both pre-diabetes and diabetes is based on glucose criteria; the common modalities used are fasting plasma glucose (FPG) test and oral glucose tolerance test (OGTT). A glucometer is commonly used by diabetic patients to measure blood glucose levels with fast and rather accurate measurements. A few of the more advanced and minimally invasive modalities include the glucose-sensing patch, SwEatch, eyeglass biosensor, breath analysis, etc. Despite a considerable amount of data being collected and analyzed regarding diabetes, the actual molecular mechanism of developing type 2 diabetes mellitus (T2DM) is still unknown. Both genetic and epigenetic factors are associated with T2DM. The complications of diabetes can predominantly be classified into two categories: microvascular and macrovascular. Retinopathy, nephropathy, and neuropathy are grouped under microvascular complications, whereas stroke, cardiovascular disease, and peripheral artery disease (PAD) belong to macrovascular complications. Unfortunately, until now, no complete cure for diabetes has been found. However, the treatment of pre-diabetes has shown significant success in preventing the further progression of diabetes. To prevent pre-diabetes from developing into T2DM, lifestyle intervention has been found to be very promising. Various aspects of diabetes, including the aforementioned topics, have been reviewed in this paper.
|
|
| 43. |
|
|
| 44. |
- Kurki, MI, et al.
(författare)
-
FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
-
Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
