Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

Randomized, sham-controlled trial of acupuncture for post-cataract surgery dry eye disease.

PURPOSE: To determine the efficacy of acupuncture in patients with post-cataract surgery dry eye disease (DED). METHODS: Ninety participants with post-cataract surgery DED were randomly assigned (1:1) to receive true acupuncture (n = 44) or non-penetrating sham acupuncture (n = 46) twice weekly for 8 weeks. The primary outcome was the change from baseline to week 8 in the noninvasive tear film break-up time (TFBUT). Participants were followed until week 12. Secondary outcomes included Ocular Surface Disease Index (OSDI) score, tear meniscus height (TMH), corneal fluorescein staining (CFS) score, meiboscore and corrected distance visual acuity (CDVA). RESULTS: The estimated mean change from baseline in the noninvasive TFBUT was 1.52 for true acupuncture versus 0.77 for sham acupuncture (adjusted difference -0.75 [95% CI -1.39 to -0.12]; P = 0.02) at week 8 and 1.49 for true acupuncture versus 0.81 for sham acupuncture (adjusted difference -0.68 [95% CI, -1.29 to -0.07]; P = 0.029) at week 12. The mean change in the OSDI score was -20.13 for true acupuncture versus -13.44 for sham acupuncture (adjusted difference 6.69 [95% CI, 0.64 to 12.74]; P = 0.031) at week 8, but revealed no statistically between-group differences at week 12. Mean changes in TMH, CFS score, meiboscore and CDVA did not differ significantly between the two groups. CONCLUSIONS: Among patients with post-cataract surgery DED, acupuncture compared with sham acupuncture resulted in statistically significant benefit on tear film stability. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800020132).

Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates.

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 â€‹cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 â€‹cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn's Disease Rats Treated with Herb-Partitioned Moxibustion.

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.

Spinal Microglia and Astrocytes: Two Key Players in Chronic Visceral Pain Pathogenesis.

Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include vascular mechanisms, mechanical factors, persistent inflammation, and unexplained functional mechanisms. Although the pathogenesis is unclear, more and more research has begun to shift from the neuronal aspect to the glial cells in recent years. Some data highlight that the spinal glial cells, particularly the microglia and astrocytes, play an essential role in CVP. Based on this, we highlight the mechanisms of microglia and astrocytes in CVP concerning the release of cytokines, chemokines, and neuroactive substances and alterations in intracellular signaling pathways during the process. Finally, because CVP is widespread in various diseases, we present future perspectives targeting microglia and astrocytes for treatment.