NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. METHOD: Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. RESULTS: The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. CONCLUSIONS: NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.

A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression.

PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI). METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes. RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups. CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.

JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice.

AIM: To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice. MATERIALS AND METHODS: The KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. KEY FINDINGS: JTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabetic mice were not significantly different. SIGNIFICANCE: We demonstrate that cathepsin K expression is increased in KK-Ay diabetic mouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures.

Screening of microorganisms from deep-sea mud for Antarctic krill (Euphausia superba) fermentation and evaluation of the bioactive compounds.

Twelve kinds of strains were isolated from deep-sea mud which can use Antarctic krill powder as the sole carbon/nitrogen source. These strains were identified by 16s rDNA sequence analysis and grouped into eight different genera, including Bacillus, Shewanella, Psychrobacter, Klebsiella, Macrococcus, Aeromonas, Acinetobacter, and Saccharomyces. After fermentation of Antarctic krill powder using these strains, bioactive compounds including total phenolics, free amino acids, and enzyme activities were investigated. Meanwhile, antioxidant activities of the fermentation liquors were also detected. Results showed that bioactive compounds could be effectively produced through fermentation process by these strains, of which three strains (Bacillus subtilis OKF04, Macrococcus caseolyticus OKF09, and Aeromonas veronii OKF10) could produce more than 650 mg/L total phenolics or 2000 mg/L total free amino acids. In terms of enzyme activities, almost all of the strains showed protease activity and amylase activity, but only Bacillus cereus OKF01 and Bacillus megaterium OKF05 performed lipase activity and chitinase activity, respectively. All of the fermentation liquors showed antioxidant activity, within which Bacillus megaterium OKF05, Macrococcus caseolyticus OKF09, and Aeromonas veronii OKF10 displayed it more prominently. These results demonstrate that the Antarctic krill powder could be effectively converted by microorganisms isolated from deep-sea mud for production of bioactive compounds mixture.

Antioxidant properties of bio-active substances from shrimp head fermented by Bacillus licheniformis OPL-007.

Antioxidative activities were found in the culture supernatant of Bacillus licheniformis OPL-007 using shrimp head waste (SHW) as the sole carbon and nitrogen source. After optimizing fermentation conditions, some bio-active substances were determined from the broth. The contents of total phenols, polysaccharides, reducing sugars, free amino acids, and organic acids were 888.80, 402.74, 85.88, 2,061.79, and 5,426.74 mg/l, respectively. Moreover, the fermentation liquid was found rich in eight essential amino acids and non-protein amino acids. The antioxidant activity of the culture supernatant, in terms of the scavenging activity of DPPH radicals, reducing power, and metal chelating ability, was monitored, and the fermentation liquid showed a strong antioxidant capacity. The results indicate that bio-deproteinization of SHW by B. licheniformis OPL-007 can increase its antioxidant activity, and SHW has the potential application in the production of functional foods.

A novel dextran dextrinase from Gluconobacter oxydans DSM-2003: purification and properties.

Dextran has already been widely applied in food, pharmaceutical, and chemical industries. In this study, a novel intracellular dextran dextrinase (DDase, EC 2.4.1.2) from Gluconobacter oxydans DSM-2003 exhibiting catalytic activity to synthesize dextran from maltodextrin was purified to homogeneity by ultrasonic cell disruption, ion exchange chromatography, and gel filtration. This procedure showed 187.5-fold purification from the cell-free extract with 41.9 % yield. And the apparent molecular weight was estimated to be 62 kDa by SDS-PAGE. It was different from the reported literatures, which found that the molecular weight of intracellular and extracellular DDase of G. oxydans ATCC-11894 was 300 and 152 kDa, respectively. Otherwise, it showed different physicochemical characteristics (optimal temperature and pH, thermal, pH stability, effect of metal ions) from the DDase of G. oxydans ATCC-11894. This indicated that DDase of G. oxydans DSM-2003 was a novel one compared to the reported literatures.