GPNMB (Glycoprotein Nmb)

Multiple therapeutic strategies targeting the GPNMB-RYK axis-including vaccination, short hairpin RNA, neutralizing antibody and N-acetylgalactosamine small interfering RNA-effectively prevented and treated MASH in preclinical models. Our findings identify the GPNMB-RYK axis as a new pathogenic ligand-receptor pathway and a promising therapeutic target for MASH.

GPNMB is a robust translatable PD biomarker for clinical trials with the PIKfyve inhibitor VRG50635. TRIAL REGISTRATION: Clinical trial number: VGCS-50635-001 and VGCS-50635-003; identifier: NL81735.056.22 and NCT06286475.

All patients with follow-up data were alive without evidence of disease progression. Our findings expand the clinical, histologic, immunohistochemical, and molecular spectrum of ELOC-mutated RCC and further support its classification as a distinct renal neoplasm.

Importantly, the pro-pyroptotic effect of GPNMB overexpression in Hcy-treated THP-1-derived macrophages was counteracted by either inhibition of NADPH oxidase 2 (NOX2) using the specific inhibitor gp91ds-tat or blockade of NF-κB activation with the inhibitor BAY11-7082. Moreover, serum GPNMB levels were correlated with serum Hcy levels and lipid profiles in both healthy individuals and HHcy patients. Collectively, these findings demonstrate that GPNMB facilitates Hcy-induced macrophage pyroptosis associated with the upregulation of the NOX2/NF-κB signaling pathway, highlighting the potential relevance of GPNMB as a candidate target for the clinical management of HHcy-related atherosclerotic cardiovascular disease.

Next-generation sequencing-based molecular profiling had clinical utility in two-thirds of patients, and the greatest benefit was within the broad category of ccRCN. Our results suggest that GPNMB expression was helpful in separating ELOC-RCCfms from M/TSC-RCCfms. Other benefits of NGS include subtyping high-grade RCC/RCC type not otherwise specified and identification of rare phenotypes.

GPNMB is widely expressed in neurons and microglia in human brain, with more expression in microglia, particularly in Parkinson's disease brain.iPSC-derived microglia (iMicroglia) secrete GPNMB in response to neurodegeneration-related insults, and iMicroglia-derived GPNMB enhances development of alpha-synuclein pathology in iNeurons.Anti-GPNMB antibodies rescue iNeurons from development of synuclein pathology. Expression quantitative trait loci (eQTLs) for GPNMB associate with extent of alpha-synuclein pathology in human neurodegenerative disease.

MSA exhibited a significant imbalance in KYN metabolism, suggesting a shift toward inflammatory processes distinct from classic neuroinflammatory markers.

P1, N=30, Not yet recruiting, Canadian Cancer Trials Group | Trial completion date: Jun 2029 --> Sep 2033

In TFE3-rearranged RCC, the fusion gene might influence morphology or PD-L1 expression, thereby be likely to affect the efficacy of immunotherapy. Assessment of a combination of histological morphology, immunophenotype, and genetic alterations can facilitate precise pathological diagnosis of RCC, supporting personalized targeted therapy and prognosis assessment.

Compared with those of the Liuwei Dihuang Pills group, the expression level of p62, FcγRⅡB, SHP-1, and c-Src in the Liuwei Dihuang Pills + LV-shGPNMB group was significantly increased, and the level of LC3Ⅱ/LC3Ⅰ was significantly decreased. These results indicate that Liuwei Dihuang Pills can inhibit the FcγRⅡB/c-Src pathway by up-regulating the GPNMB expression, thereby increasing autophagy levels, enhancing neuroprotective ability, and alleviating Alzheimer's disease.

Testicular/paratesticular updates address diagnostic criteria for mesothelium-derived lesions of the tunica vaginalis, recommended immunohistochemical panels for testicular sex cord-stromal tumors, and recommended nomenclature, specifically the use of "embryonic-type neuroectodermal tumor" rather than primitive neuroectodermal tumor (PNET) in the context of somatic transformation of testicular germ cell tumors. For penile squamous cell carcinoma, the summary emphasizes prognostic biomarkers, notably TP53 alterations and high risk HPV status, and nuances pertaining to pathologic staging.

Our report highlights that fibroma-like PEComa can serve as an early indicator of occult TSC and underscores the diagnostic utility of GPNMB immunohistochemistry as a surrogate marker of TSC1/2/MTOR pathway activation. Comprehensive clinical and genetic evaluation for TSC is recommended upon diagnosis of this rare tumor.