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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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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.
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- Chi, TG, et al.
(författare)
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Non-Coding RNA as Biomarkers for Type 2 Diabetes Development and Clinical Management
- 2021
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12, s. 630032-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes, a metabolic disease characterized by high blood glucose and other complications, has undefined causes and multiple risk factors, including inappropriate diet, unhealthy lifestyles, and genetic predisposition. The two most distinguished types of diabetes are type 1 and type 2 diabetes, resulting from the autoimmune impairment of insulin-generating pancreatic β cells and insulin insensitivity, respectively. Non-coding RNAs (ncRNAs), a cohort of RNAs with little transcriptional value, have been found to exert substantial importance in epigenetic and posttranscriptional modulation of gene expression such as messenger RNA (mRNA) silencing. This review mainly focuses on the pathology of type 2 diabetes (T2D) and ncRNAs as potential biomarkers in T2D development and clinical management. We consolidate the pathogenesis, diagnosis, and current treatments of T2D, and present the existing evidence on changes in multiple types of ncRNAs in response to various pathological changes and dysfunctions in different stages of T2D.
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- Chi, TG, et al.
(författare)
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PPAR-γ Modulators as Current and Potential Cancer Treatments
- 2021
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 737776-
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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.
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- Ji, MF, et al.
(författare)
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Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 12787-
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Tidskriftsartikel (refereegranskat)abstract
- Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35–64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.
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- Tan, Y, et al.
(författare)
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PPAR-α Modulators as Current and Potential Cancer Treatments
- 2021
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 11, s. 599995-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is one of the leading causes of mortality worldwide. PPAR modulators may hold great potential for the management of cancer patients. Indeed, PPARs are critical sensors and regulators of lipid, and they are able to promote eNOS activation, regulate immunity and inflammation response, and affect proliferation and differentiation of cancer cells. Cancer, a name given to a group of diseases, is characterized by multiple distinctive biological behaviors, including angiogenesis, abnormal cell proliferation, aerobic glycolysis, inflammation, etc. In the last decade, emerging evidence has shown that PPAR-α, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. Therefore, the multi-functional PPAR modulators have substantial promise in various types of cancer therapies. This review aims to consolidate the functions of PPAR-α, as well as discuss the current and potential applications of PPAR-α agonists and antagonists in tackling cancer.
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- Wang, MN, et al.
(författare)
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Diagnostic and Prognostic Value of Circulating CircRNAs in Cancer
- 2021
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Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 8, s. 649383-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer has been regarded as one of the leading causes of mortality worldwide. Diagnostic and prognostic biomarkers with high sensitivity and specificity for cancer play a crucial role in preventing or treating cancer. Circular RNAs (circRNAs), which hold great potential for the management of cancer patients due to their abundance, stable property, and high specificity in serum, plasma, and other body fluids, can be used as non-invasive and blood-based biomarkers in cancer diagnosis and prognosis. There are four types of circRNAs including exonic circRNAs (ecircRNA), intronic circRNAs, exon-intron circRNAs (EIciRNA), and intergenic circRNAs. CircRNAs can act as miRNA sponges, affect protein translation, interplay with RNA binding proteins, regulate protein recruitment, and modulate protein scaffolding and assembly. Therefore, the multifunctionalities of circRNAs make them ideal for detecting and predicting cancer. Indeed, circRNAs manifest high sensitivity and specificity in more than ten types of cancer. This review aims to consolidate the types and functions of circRNAs, as well as discuss the diagnostic and prognostic value of circulating circRNAs in cancer.
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- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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