RGS1 mediates renal interstitial fibrosis through activation of the inflammatory response.

Renal interstitial fibrosis (RIF) is considered as a common pathway for all patients with chronic kidney disease (CKD) to progress to end-stage kidney disease (ESRD). The basic pathological manifestation is the increase of matrix component in the tubular interstitium, while the injury of tubular epithelial cells in the renal interstitium and the excessive accumulation of matrix will eventually lead to tubular atrophy and obstruction, loss of effective renal units, and finally impaired renal filtration function. The relevant mechanism of RIF remains unclear. The present study will investigate the function and relevant mechanism of RGS1 in RIF. The RIF-related microarrays GSE22459 and GSE76882 were downloaded and analyzed. Renal parenchymal atrophic calyx tissues were collected from clinical RIF patients. Cellular inflammation, fibrosis and animal RIF models were constructed using Lipopolysaccharide (LPS), TGF-ß1 and unilateral ureteral occlusion (UUO). HE and Masson staining were performed to detect morphological alterations of renal tissue samples. qRT-PCR, Western blot and ELISA were carried out to detect the expression of relevant genes/proteins. RGS1 is a gene co-differentially expressed by GSE22459 and GSE76882. RGS1 expression was elevated in renal tissues of RIF patients, cells and animal RIF models. Knockdown of RGS1 inhibited renal cell inflammatory response, fibrosis and renal fibrosis in RIF mice. Overexpression of RGS1 plays the opposite role. Knockdown of RGS1 inhibited the inflammatory response in the RIF cell and mouse model. Targeting RGS1 might be a potential therapeutic strategy for RIF treatment.

Constructing an immune- and ferroptosis-related lncRNA signature to predict the immune landscape of human bladder cancer.

BACKGROUND: LncRNAs play a variety of roles in the tumor microenvironment and cancer immune responses. Determining the significance of bladder cancer (BLCA)-related genes to predict the prognostic and therapeutic response of BLCA is important. METHODS: IrlncRNA/ frlncRNA pairs were determined using univariate analysis. The signature was constructed based on this pairs. Finally, analysis and internal validation were performed from several aspects. RESULTS: We identified 60 immune- and ferroptosis-related lncRNA pairs, among which 12 were included in the Cox proportional hazards model. Patients in low-risk group survived for significantly longer. Survival and riskScore analyses showed that the low-risk group had a significantly better clinical outcome. ROC curve analysis showed that AUC of OS values were more than 0.75 in the training set and the whole cohort. As assessed using Cox analysis, the riskScore was an independent prognostic predictor in the training, testing set and the whole cohort. The areas under the multi-index ROC in the training set, the testing set, and the whole cohort were 0.777, 0.692, and 0.748, respectively. High-risk group was positively associated with most of tumor-infiltrating immune cells. High-risk Scores correlated positively with high expression of CD274, but not with PD-1. Low riskScores correlated positively with high expression levels of the genes ERBB2 and nectin-4. High-risk Score was associated with a lower IC50 value for Docetaxel, cisplatin, and Pazopanib, while there was an opposite result for metformin. CONCLUSIONS: The signature constructed by pairing irlncRNAs and frlncRNAs showed a notable clinical predictive value.

[UPOINT: a novel phenotypic classification system for chronic prostatitis/chronic pelvic pain syndrome].

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition obsessing urologists and patients. It is also known as a heterogeneous syndrome, with varied etiologies, progression courses and responses to treatment. Based on the deeper insights into its pathogenesis and re-evaluation of its clinical trials, a novel phenotypic classification system UPOINT has been developed, which clinically classifies CP/CPPS patients into six domains: urinary (U), psychosocial (P), organ-specific (O), infection (I) , neurologic/systemic (N) and tenderness of pelvic floor skeletal muscles (T), and directs individualized and multimodal therapeutic approaches to CP/CPPS. This review systematically summarizes the theoretical foundation, clinical characteristics of UPOINT and treatment strategies based on the UPOINT phenotypic classification system.

[Effect of RelB-silenced BMDC pulsed with Talpha146~162 on immunoreaction of T cells primed with TAChR].

OBJECTIVE: To investigate whether RelB-silenced bone marrow-derived dendritic cells (BMDC) pulsed with torpedo acetylcholine receptor (TAChR) immuno-dominant peptide Talpha146~162 can induce tolerance in T cells primed with TAChR. METHODS: Recombinant lentivirus that produced RelB siRNA and control lentivirus were prepared and used to infect BMDCs. The infected BMDCs were stimulated with LPS,and the resulting cells were designated as DC-siRelB or DC-control, respectively. The mRNA and protein expression of RelB were examined by quantitative real-time PCR and Western blot. Cell surface markers of DC were evaluated by flow cytometry. IL-12 in the supernatant was detected by ELISA. Mice were randomly divided into 6 groups: A1, A2, A3,K1, K2, and K3. On day 0, group A1, A2, and A3 were primed with TAChR in CFA and group K1, K2 and K3 were primed with KLH+CFA. On day 7, group A2 and K2 were injected with Talpha146~162 pulsed DC-siRelB, group A3 and K3 were injected with Talpha146~162 pulsed DC-control, while A1 and K1 group received PBS at the same time. On day 14, lymphocyte proliferative response of the 4 groups were measured. RESULTS: Recombinant lentivirus including RelBshRNA genes was successfully constructed. RelB siRNA knocked down RelB expression in BMDCs obviously. Compared with DC-control, DC-siRelB expressed a significantly lower level of CD80, CD86, and MHC class II on their surface, producing lower level of IL-12. Compared with group A1 and A3, lymphocyte proliferative response to TAChR of A2 group was suppressed significantly (P<0.05). No different lymphocyte proliferative responses to KLH and ConA were seen in group A1, A2 and A3 (P>0.05). No different lymphocyte proliferative responses were seen in group K1, K2 and K3 (P>0.05). CONCLUSION: Lentiviral-mediated RelB-silenced BMDCs are maturation resistant and can induce antigen-specific tolerance in TAChR primed C57BL/6 mice,which provides a basis for further study of their therapeutic potential in myasthenia gravis.