Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Imidazoles/administration & dosage* ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Metastasis ; Oximes/administration & dosage* ; Proto-Oncogene Mas ; Proto-Oncogene Proteins B-raf/genetics* ; Pyridones/administration & dosage* ; Pyrimidinones/administration & dosage*

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

"State-target-cause-result"is a new clinical theory combining macroscopic and microscopic syndrome differentiation based on the holistic view of traditional Chinese medicine combined with Western medical research.The"inflammation-cancer transformation"of chronic pancreatitis is a complex pathological process that is associated with the interaction between the pancreas and various pathological factors and multiple objects,involving the imbalance of multiple homeostasis.The microscopic process of"inflammation-cancer transformation"in chronic pancreatitis is the"target,"whereas various factors that could induce its occurrence under chronic inflammatory conditions are the"state."The"inflammation-cancer transformation"of chronic pancreatitis is summarized as yin and yang imbalance,qi movement disorder,endogenous dampness,heat,blood stasis,and turbid phlegm stagnation,unresolved congestion resulting in deficiency caused by stagnation,intermingled deficiency and excess,and internal cancer toxin generation.This paper elucidates the pathogenesis and intervention strategies of the"inflammation-cancer transformation"of chronic pancreatitis from a macro perspective of"state,"focusing on reducing the impact of"state"imbalance on the"target"to establish a balanced pancreas-immune-microbiota state.The aim is to broaden the theory for exploring the mechanism and drug development related to chronic pancreatitis"inflammation-cancer transformation"in both traditional Chinese and Western medicine.

On May 25, 2024, Shanghai Municipal Administration for Market Regulation released Shanghai local standard Requirements for Outdoor Smoking Areas Setting Up and Management (DB 31/T 1482‒2024) (hereinafter referred to as Standard), which scheduled for official implementation from September 1, 2024. This article provided an interpretation of the key provisions in the Standard, with a particular emphasis on the scope of application, establishment and management requirements. In addition, the significance and potential difficulties and challenges during subsequent implementation of the Standard was summarized and outlined simultaneously, so as to provide a guarantee for users to fully comprehend and effectively implement the Standard.

Immuno-actinopathies are hereditary diseases characterized by immunodeficiency and immune dysregulation due to the mutations in single genes which are regulating actin remodeling. Mutations in actin-related regulatory genes can lead to functional defects in actin activation, extension, branching, transcription and others. The mutations also affect the cytoskeleton and pseudopod formation; then they further affect the functions of immune cell, resulting in cell deformation, motility, phagocytosis, and adhesion. The clinical manifestations vary, including infection, autoimmunity, autoinflammatory, and susceptibility to tumors, making the detection and diagnosis difficult. The pathogenic mechanisms of some of the related diseases have been preliminarily elucidated. Future research will focus on the identification of new immunoactinopathy-caused genes and its mechanism, discovery of new precision therapeutic target, development of drugs, improvement of hematopoietic stem cell transplantation strategies, and discovery of new gene therapy. Immuno-actinopathies have a low incidence rate with diversified clinical manifestations so that they are easy to be misdiagnosed and missed. This article reviews the pathogenic gene defects of actinopathies and their clinical manifestations in detail that are valuable to clinical reference.

JAK-STAT signaling pathway is an important cytokine signaling transduction pathway. Many monogenic loss-of-function or gain-of-function mutations in this pathway can cause inborn errors of immunity (IEI). Autoimmune diseases are caused by polygenic and different factors.The etiology of the disease is complex and diverse. The over-activation of JAK-STAT signaling pathway plays a significant role in the pathogenesis of autoimmune diseases. In this article, we summarize the mechanism of the JAK-STAT pathway and its role in the occurrence and development of IEI and autoimmune diseases, suggesting that the hyperactivation of JAK-STAT pathway having connection with IEI and autoimmune diseases. Meanwhile, we hope to make IEI a good model to study the pathogenesis of autoimmune diseases and to provide new ideas and directions for the clinical treatment of autoimmune diseases.

With the increasing emphasis on the bio-psycho-social medical model, significant progress has been made in patient-reported outcomes. Now, through a comprehensive analysis and synthesis of literature within the field, this study explores the advancements in the application of patient-reported outcomes in clinical research on lymphoma. The intention is to provide valuable references for future related studies.

Objective:To explore the effect of long non-coding RNA (lncRNA) C10orf25 on the proliferation and invasion ability of prostate cancer cells and the possible role of miRNA-671-5p (miR-671-5p).Methods:Data from the Gene expression omnibus (GEO) database (data updated in January 2023) were used to analyze the differences in the expression levels of C10orf25 in 137 cases of prostate cancer tissues and paracancerous tissues. Prostate cancer C4-2B, DU-145, 22Rv1, PC-3, LNCaP cell lines and immortalized prostate epithelial RWPE-1 cell lines were selected, and then real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of C10orf25 in cell lines. The 22Rv1 cells with the lowest relative expression level of C10orf25 were selected and divided into the control group (transfected with negative plasmid) and the C10orf25 group (transfected with C10orf25 plasmid); the CCK-8 method was used to detect the proliferation activity of 22Rv1 cells in both groups at day 1, 2, 3, 4, 5 (expressed as absorbance value); the Transwell method was used to detect the invasion ability of 22Rv1 cells. Linc2GO software was used to predict miR-671-5p with binding sites for C10orf25. Dual luciferase reporter gene assay was used to verify the targeting relationship between C10orf25 and miR-671-5p. qRT-PCR was used to detect the relative expression levels of C10orf25 and miR-671-5p. Western blot was used to detect the expression of proteins related to the NF-κB signaling pathway of 22Rv1 cells in the both groups.Results:In the GEO database, the relative expression level of C10orf25 in prostate cancer tissues was lower than that in paracancerous tissues ( P < 0.01). The relative expression levels of C10orf25 in immortalized prostate epithelial cell line RWPE-1 and prostate cancer cell lines C4-2B, DU-145, 22Rv1, PC-3, and LNCaP were 1.00±0.05, 0.63±0.04, 0.42±0.03, 0.18±0.04, 0.81±0.02, 0.50±0.07, and the difference was statistically significant ( F = 43.29, P < 0.05). The proliferation ability of 22Rv1 cells in C10orf25 group was lower than that in the control group from the second day, and the differences were statistically significant (all P < 0.05). The number of invasive cells in the control group and C10orf25 group were (97±11) and (36±9), respectively, and the difference was statistically significant ( t = 4.15, P < 0.01). Linc2GO software prediction results showed that C10orf25 had a binding site for miR-671-5p. The dual luciferase reporter gene assay showed that the relative luciferase activity of miR-671-5p and C10orf25 wild plasmid co-transfecting 22Rv1 cells was lower than that of miR-NC and C10orf25 wild plasmid co-transfecting 22Rv1 cells, and the difference was statistically significant ( P < 0.01); when miR-671-5p or miR-NC was co-transfected with C10orf25 mutant plasmid, the difference in the luciferase activity of 22Rv1 cells was not statistically significant ( P > 0.05). The relative expression levels of miR-671-5p in 22Rv1 cells were 7.33±0.99 and 0.98±0.16, respectively in the control group and C10orf25 group, and the difference was statistically significant ( t = 6.32, P < 0.01). The results of Western blot showed that the expression levels of NF-κB signaling pathway protein p50, matrix metalloproteinase 9, c-myc, and vascular endothelial growth factor protein in 22Rv1 cells in C10orf25 group were lower than those in the control group. Conclusions:The overexpression of C10orf25 may inhibit the proliferation and invasion of prostate cancer cells through the miR-671-5p-NF-κB axis.