PRDX6 alleviates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis.

OBJECTIVE: Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin 6 (PRDX6) is an antioxidant enzyme identified as a regulator in ferroptosis. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS)-induced inflammation and its mechanisms. MATERIAL AND METHODS: Both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and nuclear factor erythropoietin 2-related factor 2 (NRF2) by Immunohistochemistry and Western blotting. Furthermore, the molecular mechanisms of PRDX6 have been clarified in PRDX6 silenced cells. The inflammatory cytokines in HGFs were measured by RT-qPCR and ELISA. The lipid hydroperoxide (LOOH) was detected by C11-BODIPY. RESULTS: The expression of PRDX6 and NRF2 were decreased in gingival tissues of severe periodontitis patients. The increased LPS-induced LOOH and inflammatory cytokines were found in PRDX6 knockdown HGFs. Besides, the inhibition of ferroptosis or PRDX6 phospholipase A2 activity (PLA2) alleviated LPS-induced inflammatory cytokines and LOOH. However, inhibiting NRF2 signalling upregulated those in HGFs. CONCLUSIONS: Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signalling, alleviates LPS-induced inflammation and ferroptosis in human gingival fibroblasts.

The role of non-coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential.

Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in the world, arises from the interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5-fluorouracil, and paclitaxel have now become the first-line options for OSCC patients. Nevertheless, most OSCC patients eventually acquire drug resistance, leading to poor prognosis. With the discovery and identification of non-coding RNAs (ncRNAs), the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized. The mechanisms of drug resistance of OSCC are intricate and involve drug efflux, epithelial-mesenchymal transition, DNA damage repair, and autophagy. At present, strategies to explore the reversal of drug resistance of OSCC need to be urgently developed. Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting, controlled release, and consistent pharmacokinetic profiles. In particular, the combined application of new technologies (including CRISPR systems) opened up new horizons for the treatment of drug resistance of OSCC. Hence, this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC, elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC, and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC.

Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury.

Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up- and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.

SIRT 1 binding with PKM and NSE and modulate their acetylation and activities.

SIRT1 (Silent mating type information regulation 2 homolog 1) play a neuroprotective effect through deacetylation target proteins in various neuronal diseases. However, the precise mechanisms remain elusive. In this study, we aim to identify those novel interacting partners of SIRT1 in rat brain tissue. By using a pre-clear GST-Pull down assay followed by the LC-MS/MS analysis, we've identified potential SIRT1's interacting partners, which function annotation by GO and KEGG analysis indicating some metabolic pathways are among the most enriched. Then we confirmed two candidates Enolase-1 (and NSE (Neuron-Specific Enolase) in brain) and PKM (Pyruvate Kinase Muscle) are associated with SIRT1 in brain tissue lysis by co-immunoprecipitation. Furthermore, increase or decrease the SIRT1 enzyme activity by its agonist SRT1720 or antagonist EX527 could significantly affect the acetylation level of endogenous NSE and PKM, SIRT1 overexpression or knock out expreiments also showed the same results as use SIRT1's agonist or antagonist. Moreover, the acetylation changes on NSE or PKM could finally lead to affection on their catalytic activity. Taken together, our findings suggest that the function of SIRT1 binding proteins is enriched in metabolic pathways. NSE and PKM are new SIRT1 binding molecules. SIRT1 may regulate acetylation level of NSE and PKM through deacetylation and further regulate their catalytic activity. Our study provides new evidence for the involvement of SIRT1 in the mechanisms of metabolic regulation in central nervous system.

[Effect of Chuanhuang No. 1 recipe on renal function and micro-inflammation in phase 3 chronic kidney disease patients].

OBJECTIVE: To observe the effect of Chuanhuang No.1 Recipe (CHR) on renal function and micro-inflammation in phase 3 chronic kidney disease (CKD) patients. METHODS: Totally 60 phase 3 CKD patients were randomly assigned to the treatment group (treated by CHR) and the control group (treated by Losartan Potassium), 30 in each group. All patients received basic treatment. Patients in the treatment group took CHR decoction, 400 mL each time, one dose per day, while those in the control group took Losartan Potassium, 50-100 mg per day. All medication lasted for 24 weeks. Changes of serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), serum uric acid (UA), 24 h urinary protein excretion (24 h U-pro), urinary microalbumin (U-Alb), high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor (TNF)-alpha, and serum IL-6 were detected and compared before and after treatment. Efficacy was also compared. RESULTS: Compared with before treatment, SCr and BUN significantly decreased in the treatment group (P<0.05, P<0.01); eGFR in- creased (P<0.05). Only UA obviously decreased in the control group (P<0.05), but with no obvious change in SCr, BUN, or eGFR. Compared with before treatment, 24 h U-pro decreased after treatment in the treatment group (P<0.05), but with less decreased level when compared with the control group. U- Alb was also significantly decreased in the control group (P<0.01). There was statistical difference in 24 h U-pro and U-Alb between the two groups after treatment (P<0.05). Compared with before treatment, hs-CRP obviously decreased after treatment in the two groups, but serum levels of TNF-alpha and IL-6 obviously decreased only in the treatment group (P<0.05). The total effective rate was obviously higher in the treatment group than in the control group (70.00% vs. 43.33%, P<0.01). CONCLUSION: CHR could efficiently improve the renal function of phase 3 CKD patients and alleviate the micro-inflammation.