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Background: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5’,6,6’-Tetrachloro-1,1’,3,3’-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2’,7’-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. Results: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3’UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to ‘CUGUUGA’ in 3’UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. Conclusion: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

The role of crescent formation in primary membranous nephropathy (PMN) and its potential impact on prognosis remain an area of ongoing investigation. This study stratifies patients with PMN into two cohorts: one with crescents and one without. It then compares these groups to investigate the influence of crescents on the prognosis of PMN. In this retrospective analysis, we included patients who had a confirmed diagnosis of PMN and exhibited crescents upon renal biopsy. The study population was sourced from the medical records at the Affiliated Hospital of Guangdong Medical University in Zhanjiang, China, spanning from January 2017 to June 2023. To enable a comparative analysis of clinical, pathological, and prognostic features, a control group was established, comprising 106 patients diagnosed with PMN who did not have crescent formation. These controls were randomly selected from the same time frame. Regular follow-up of the patients continued in the outpatient setting for at least six months. A total of 53 patients with PMN and crescent formation were included in this study, while 106 individuals without crescents served as a randomly selected control group. Patients with PMN and crescents exhibited higher systolic blood pressure ( = 0.015), 24-hour proteinuria ( = 0.006), serum creatinine ( = 0.029) levels, and lower glomerular filtration rate ( = 0.002), compared to those without crescents. Histological examination revealed a higher proportion of focal segmental sclerosis ( < 0.001), spherical sclerosis ( < 0.001), arteriosclerosis ( = 0.02), and interstitial fibrosis with tubular necrosis ( = 0.002) in patients with PMN and crescent formation. Immunofluorescence staining demonstrated a weaker IgG4 fluorescence intensity in patients with PMN and crescent formation. At the end of the follow-up period, patients with PMN and crescents had a lower remission rate ( = 0.022), poorer renal function ( = 0.007), and lower albumin ( = 0.039) levels. Kaplan-Meier (KM) analysis identified proteinuria and crescent formation as independent risk factors for adverse outcomes in patients with PMN ( < 0.001 and < 0.05). Immunohistochemistry staining revealed positive expression of CD68 and CD20 in the renal interstitium of patients with PMN, regardless of the presence of crescents. Crescent formation is associated with a risk of adverse outcomes in patients with PMN. Patients with crescents exhibit severe clinical and pathological features and have poorer prognoses.

Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive. In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population. The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique. Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008–1.811, P=0.044) compared with C allele. Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06–4.989, P=0.035). Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels. Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls. In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD.

Bone cancer pain is a common symptom in cancer patients with bone metastases and the underlying mechanisms are largely unknown. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategies for bone‐cancer induced pain (BCIP) as a result of metastases. MRMT‐1 tumor cells were injected into bilateral tibia of rats and X‐rays showed that the area suffered from bone destruction, accompanied by an increase in osteoclast numbers. In addition, rats with bone cancer showed apparent mechanical and thermal hyperalgesia at day 28 after intratibial MRMT‐1 inoculation. However, intrathecal injection of morphine or lentivirus‐mediated glial cell line‐derived neurotrophic factor RNAi (Lvs‐siGDNF) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail‐flick latencies, respectively. Furthermore, Lvs‐siGDNF interference not only substantially downregulated GDNF protein levels, but also reduced substance P immunoreactivity and downregulated the ratio of pERK/ERK, where its activation is crucial for pain signaling, in the spinal dorsal horn of this model of bone‐cancer induced pain. In this study, Lvs‐siGDNF gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs‐siGDNF to relieve pain was similar to morphine, but it is not a narcotic, the use of GDNF RNA interference may be considered as a new therapeutic strategy for the treatment of bone cancer pain in the future. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategy for bone cancer pain induced by metastases. The effect of Lvs‐siGDNF to relief pain was similar the effect from morphine administration. GDNF RNAi therefor might be considered as a new therapeutic strategy for bone cancer pain treatment in the future.