Türkçeden garp dillerine tercümeler

Taha Toros Arşivi, Dosya Adı: Namık Kemalİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index 1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance

Role of endogenous retroviruses in murine SLE

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by B cell hyperactivity leading to the production of various autoantibodies and subsequent development of glomerulonephritis, i.e. lupus nephritis. Among the principal targets of the autoantibodies produced in murine SLE are nucleic acid-protein complexes and the envelope glycoprotein gp70 of endogenous retroviruses. Recent studies have revealed that the innate receptor TLR7 plays a pivotal role in the development of a wide variety of autoimmune responses against DNA- and RNA-containing nuclear antigens, while TLR9 rather plays a protective role. In addition, the regulation of autoimmune responses against endogenous retroviral gp70 by TLR7 suggests the implication of endogenous retroviruses in this autoimmune response. Moreover, the demonstration that TLR7 is involved in the acute phase expression of serum gp70 uncovers an additional pathogenic role of TLR7 in murine lupus nephritis by promoting the expression of nephritogenic gp70 autoantigen. Clearly, the eventual identification of endogenous retroviruses implicated in murine SLE and of mouse genes regulating their production could provide a clue for the potential role of endogenous retroviruses in human SLE

TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice

The endogenous retroviral envelope glycoprotein, gp70, implicated in murine systemic lupus erythematosus (SLE), has been considered to be a product of xenotropic, polytropic (PT) and modified PT (mPT) endogenous retroviruses. It is secreted by hepatocytes like an acute phase protein, but its response is under a genetic control. Given critical roles of TLR7 and TLR9 in the pathogenesis of SLE, we assessed their contribution to the acute phase expression of serum gp70, and defined a pivotal role of the Sgp3 (serum gp70 production 3) and Sgp4 loci in this response. Our results demonstrated that serum levels of gp70 were up-regulated in lupus-prone NZB mice injected with TLR7 or TLR9 agonist at levels comparable to those induced by injection of IL-1, IL-6 or TNF. In addition, studies of C57BL/6 Sgp3 and/or Sgp4 congenic mice defined the major roles of these two loci in up-regulated production of serum gp70 during acute phase responses. Finally, the analysis of Sgp3 congenic mice strongly suggests the presence of at least two distinct genetic factors in the Sgp3 interval, one of which controlled the basal-level expression of xenotropic, PT and mPT gp70 and the other which controlled the up-regulated production of xenotropic and mPT gp70 during acute phase responses. Our results uncovered an additional pathogenic role of TLR7 and TLR9 in murine lupus nephritis by promoting the expression of nephritogenic gp70 autoantigen. Furthermore, they revealed the involvement of multiple regulatory genes for the expression of gp70 autoantigen under steady-state and inflammatory conditions in lupus-prone mice