Role of GDF-15 in diabetic nephropathy: mechanisms, diagnosis, and therapeutic potential.

PURPOSE: Growth differentiation factor 15 (GDF-15) is a cytokine involved in regulating homeostasis, and its expression is up-regulated in response to injury, stress, and inflammation. This study explored the role of GDF-15 in diabetic nephropathy (DN), a severe complication of diabetes mellitus, and its potential as a biomarker for disease progression. METHODS: As a member of the transforming growth factor-ß superfamily, GDF-15 exhibits its renal protective functions primarily through its anti-inflammatory effects and the up-regulation of other renal protective factors. This study evaluated the association between circulating GDF-15 levels and DN progression, examining the underlying mechanisms. RESULTS: Circulating GDF-15 levels are closely linked to the development and progression of DN. While existing research has yielded some consistent conclusions, a comprehensive understanding of the role of GDF-15 in DN pathogenesis is needed to identify new therapeutic targets and strategies. CONCLUSION: GDF-15 has the potential to be a prognostic and diagnostic biomarker for DN. It is crucial to establish appropriate reference ranges and explore their clinical utility in routine practice for validating the role of GDF-15 in DN management. Further interventional studies are required to confirm its clinical value in diagnosing and predicting the progression of DN.

Tumor Fibroblast-Derived FGF2 Regulates Expression of SPRY1 in Esophageal Tumor-Infiltrating T Cells and Plays a Role in T-cell Exhaustion.

T-cell exhaustion was initially identified in chronic infection in mice and was subsequently described in humans with cancer. Although the distinct signature of exhausted T (TEX) cells in cancer has been well investigated, the molecular mechanism of T-cell exhaustion in cancer is not fully understood. Using single-cell RNA sequencing, we report here that TEX cells in esophageal cancer are more heterogeneous than previously clarified. Sprouty RTK signaling antagonist 1 (SPRY1) was notably enriched in two subsets of exhausted CD8+ T cells. When overexpressed, SPRY1 impaired T-cell activation by interacting with CBL, a negative regulator of ZAP-70 tyrosine phosphorylation. Data from the Tumor Immune Estimation Resource revealed a strong correlation between FGF2 and SPRY1 expression in esophageal cancer. High expression of FGF2 was evident in fibroblasts from esophageal cancer tissue and correlated with poor overall survival. In vitro administration of FGF2 significantly upregulated expression of SPRY1 in CD8+ T cells and attenuated T-cell receptor-triggered CD8+ T-cell activation. A mouse tumor model confirmed that overexpression of FGF2 in fibroblasts significantly upregulated SPRY1 expression in TEX cells, impaired T-cell cytotoxic activity, and promoted tumor growth. Thus, these findings identify FGF2 as an important regulator of SPRY1 expression involved in establishing the dysfunctional state of CD8+ T cells in esophageal cancer. SIGNIFICANCE: These findings reveal FGF2 as an important regulator of SPRY1 expression involved in establishing the dysfunctional state of CD8+ T cells and suggest that inhibition of FGF2 has potential clinical value in ESCC. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/24/5583/F1.large.jpg.

Crossed cerebellar diaschisis detected by arterial spin-labeled perfusion magnetic resonance imaging in subacute ischemic stroke.

BACKGROUND: Crossed cerebellar diaschisis (CCD) was a common radiological phenomenon manifested as reduced blood flow and metabolism in the cerebellar hemisphere contralateral to a supratentorial cerebral lesion. The hypoperfusion and hypometabolism in the contralateral cerebellum in CCD was traditionally detected by positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The present prospective study aimed to assess the detection of CCD in subacute stage ischemic stroke by arterial spin-labeling (ASL) perfusion technique with a 3.0-T magnetic resonance imaging (MRI) scanner. METHODS: ASL images were obtained from 46 patients with supratentorial ischemic stroke at subacute stage. Regional cerebral blood flow values in the cerebellar hemispheres were measured on a region of interest basis. RESULTS: Twenty-four of 46 (52%) patients showed CCD phenomenon by ASL-MRI method, which was in line with the PET/SPECT series. Infarctions in basal ganglia areas are prone to cause CCD. CONCLUSIONS: With advantages in easy acquisition and no radiation, ASL-MRI seems to be an ideal tool for the detection and follow-up of CCD.

Morphologic characteristics of late stent malapposition after drug-eluting stents implantation by optical coherence tomography follow-up.

BACKGROUND: Late stent malapposition was frequently observed after DES implantation, which has been associated with the occurrence of late stent thrombosis due to poor neointimal coverage. This study was designed to evaluate the frequency of late stent malapposition at least 1 year after different DESs implantation by optical coherence tomography (OCT). METHODS: Angiographic and OCT examinations were given to 68 patients who had received total 126 various DESs implantation for at least 1 year to detect late stent malapposition. Malapposed strut distance (MSD), malapposed strut area (MSA), reference lumen area (RLA) and reference stent area (RSA) were checked with off-line OCT analysis. RESULTS: Totally 26 Cypher Select stents, 15 Taxus Liberte stents, 51 Partner stents and 34 Firebird I stents were examined. Among 68 patients who underwent DES implantation, 7 patients (10.3%) had late malapposition. Average RSA, MSA and MSD were (7.9 +/- 2.8) mm(2),(2.0 +/- 1.6) mm(2) and (590 +/- 270) microm respectively. According to the MSA/RSA ratio, 4 patients had slight malapposition, 2 patients had moderate malapposition and 1 patient had severe malapposition. CONCLUSIONS: Late stent malapposition is detected frequently after implantation of DES, but if this predisposes to late stent thrombosis and requires any specific therapy needs to be further elucidated.