The development of Inflammatory bowel disease (IBD) is driven by excessive production of pro-inflammatory cytokines including TNF-α, IL-12, and IL-23. This notion is supported by the remarkable clinical success of biologics targeting these cytokines. Recognition of cell wall components derived from intestinal bacteria by Toll-‍like receptors (TLRs) induces the production of these pro-inflammatory cytokines by macrophages and dendritic cells in human IBD and experimental colitis model. Although sensing of bacterial nucleic acids by endosomal TLRs, specifically TLR3, TLR7, and TLR9 leads to robust production of type I IFNs, it remains debatable whether TLR-mediated type I IFN responses are pathogenic or protective in IBD patients. Additionally, recent studies identified deubiquitinating enzyme A (DUBA) as a novel negative regulator of TLR-mediated type I IFN responses. In light of these observations and their potential applications, in this review, we summarize recent findings on the roles of type I IFN responses and DUBA-mediated negative regulation of these responses in human IBD and experimental colitis model.

Quality improvement in clinical laboratories is crucial to ensure accurate and reliable test results. With increasing awareness of ‍the potential adverse effects of errors in laboratory practice on ‍patient outcomes, the need for continual improvement of laboratory services cannot be overemphasized. A literature search was conducted on PubMed and a web of science core collection between October and February 2021 to evaluate the scientific literature quality of clinical laboratory quality improvement; only ‍peer-reviewed articles written in English that met quality improvement criteria were included. A structured template was used to extract data, and the papers were rated on a scale of 0–16 using the Quality Improvement Minimum Quality Criteria Set (QI-‍MQCS). Out of 776 studies, 726 were evaluated for clinical laboratory literature quality analysis. Studies were analyzed according to the ‍quality improvement and control methods and interventions, such as training, education, task force, and observation. Results showed that the average score of QI-MQCS for quality improvement papers from 1981–2000 was 2.5, while from 2001–2020, it was 6.8, indicating continuous high-quality improvement in the clinical laboratory sector. However, there is still room to ‍establish a proper system to judge the quality of clinical laboratory literature and improve accreditation programs within the sector.

A widespread degenerative condition of the aorta, abdominal aortic aneurysm (AAA), severely endangers the health of middle-aged and elderly people. SPARC related modular calcium binding2 (SMOC2) is upregulated in the carotid arteries of rats with atherosclerotic lesions, but its function in AAA is still unknown. Therefore, the aim of this research was to evaluate the function of SMOC2 in AAA. The results showed that in the AAA tissues, SMOC2 expression was upregulated compared with healthy controls. Over­expres­sion of SMOC2 promoted vascular smooth muscle cells (VSMCs) proliferation, migration, and extracellular matrix (ECM) degradation. In contrast, silence of SMOC2 inhibited VSMCs proliferation, migration, and ECM degradation. Over­expres­sion of SMOC2 promoted BMP and TGF-β1 expression and silence of SMOC2 had an opposite effect. Besides, inhibition of BMP or TGF-β1 suppressed VSMCs cell proliferation, migration, and ECM degradation. Moreover, inhibition BMP or TGF-β1 reversed the promotive effects of SMOC2 overexpression on VSMCs proliferation, migration, and ECM degradation. SMOC2 may affecte the formation of AAA by upregulating BMP and TGF-β1 to regulate the proliferation, migration, and ECM degradation of VSMCs.

The impact of repeated administration of cinntamtannin A2 (A2, 25 μg/kg) on skeletal muscle disuse atrophy model mice induced by hindlimb suspension for 14 days was examined. In soleus, weight loss and a reduction in the average myofibre size with shifting to the smaller side of the peak were observed in the suspension-vehicle group, but A2 reduced these changes. Average myofibre size significantly increased in ground-A2 compared to ground-vehicle. A marked increase in the dephosphorylation of forkhead box O (FoxO) 3a by the suspension was reduced by A2. The phosphorylation of protein kinase B (Akt) and eukaryotic translation initiation factor 4E-binding protein (4EBP)-1 were significantly increased by the treatment of A2. In addition, a single dose of A2 increased dramatically in the 24-h excretion of catecholamines in urine. These results suggest that A2 admin­istration results in sympa­thetic nerve activation and promotes hypertrophy while inhibiting the progress of disuse muscle atrophy.

The tripartite motif 62 is an E3 ubiquitin ligase protein that regulates cellular processes, including differentiation, immunity, development and apoptosis, leading to various disease states, such as cancer and inflammatory diseases. However, the role and mechanism of the tripartite motif 62 in the process of diabetic-induced cognitive impairment have not been reported. Therefore, the aim of this study was to investigate the role and mechanism of the tripartite motif 62 in diabetic-induced cognitive impair­ment. The results showed that the expression of the tripartite motif 62 was up-regulated in diabetic mice. Silencing of TRIM62 increased body weight and decreased fasting blood glucose in diabetic mice. In addition, knockdown of the tripartite motif 62 inhibited STZ-induced inflammation, apoptosis and oxidative stress. Further studies showed that the TLR4/NF-κB pathway and NLRP3 inflammasomes were involved in the regulation of diabetic mice by the tripartite motif 62. More importantly, inhibition of the tripartite motif 62 improved cognitive impairment and learning ability in mice. In conclusion, inhibition of TRIM62 inhibits STZ-induced inflammation, cell apoptosis and oxidative stress, and improves the cognitive ability of mice. Therefore, the tripartite motif 62 may be an important target for the treatment of diabetes-induced cognitive impairment.

We have reported that extent of proliferation of atypical hepatocytes (POAH) in non-cancerous liver in hepatocellular carcinoma and chromatin licensing and DNA replication factor 1 (CDT1) are associated with postoperative recurrence. Here, we investigated whether extent of POAH and expression of CDT1 in ‍liver are also associated with chemically induced liver cancer in ‍rats. Male Fisher strain rats were orally administered diethylnitrosamine (DEN) in their drinking water and sacrificed at 6, 8, 12, or 14 weeks after start of DEN administration. We serially monitored changes in extent of POAH, CDT1 expression by immunohistochemistry (IHC), and CDT1 mRNA expression in liver by real-time quantitative PCR. The extent of POAH in liver progressed in a time-dependent manner after start of DEN administration. CDT1 expression was higher at 8 weeks than at 6 weeks by IHC, suggesting that CDT1 expression may be a marker of POAH severity. CDT1 mRNA expression in liver was significantly higher at 12 weeks than at 6 weeks (p<0.0001). We found that extent of ‍POAH and the expression of CDT1 are also important factors in ‍the development of chemical carcinogen-induced hepato­carcinogenesis. Furthermore, the association with POAH and CDT1 expression in carcinogenic process is important regardless of the cause of hepatocarcinogenesis.

NEK7 is a serine/threonine kinase that regulates cell mitosis and the activation of the nucleotide-binding oligomerization domain-like (NOD-like) receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, and is related to neuro­inflammation and neuronal damage. The purpose of this study was to explore the role and mechanism of NEK7 in cognitive impairment in Alzheimer’s disease (AD). BV2 cells, a microglia cell line, was treated with Aβ₄₂. NEK7 expression was measured with reverse transcription–quantitative polymerase chain reaction and Western blotting. An apoptosis kit was used to determine the apoptotic rate. APPswe/PS1dE9 (APP/PS1) transgenic mice were used as an in vivo AD model. The experimental mice were infected with sh-NEK7 lentivirus to downregulate NEK7. The Morris water maze was conducted to explore the effect of NEK7 downregulation on cognitive ability. The results showed that Aβ₄₂ significantly upregulated NEK7 in BV2 cells. Silencing NEK7 suppressed the decrease in BV2 viability and the increase in inflammation, oxidative stress and apoptosis induced by Aβ₄₂. NEK7 mediated it effects through the TLR4/NF-κB signalling pathway and the NLRP3 inflammasome. Finally, inhibition of NEK7 alleviated the cognitive impairment in APP/PS1 mice. In conclusion, Silencing NEK7 suppresses Aβ₄₂-induced cell apoptosis, inflammation and oxidative stress, and improves cognitive performance in AD mice. NEK7 may be a potential target for AD treatment.

MicroRNA (miR)-499a-5p has been reported to regulate the progression of various tumours. However, the role of miR-499a-5p in breast cancer is unclear. The purpose of this study was to investigate the role and mechanism of miR-499a-5p in breast cancer. The growth effect of miR-499a-5p on breast cancer cells was investigated by the CCK-8 assay, wound healing assay and Transwell invasion assay. The luciferase activity assay was used to verify the downstream targets of miR-499a-5p. The levels of GSH, MDA, and ROS were detected by kits. Quantitative real-time PCR and Western blot were used to determine the expression levels of ‍TMEM189, COX-2, GPX4, and other related genes in cells. miR-499a-5p was down-regulated in MDA-MB-231 cells and was shown to reduced the viability, migration and invasion of MDA-MB-231 cells. Further studies revealed that TMEM189 is a target of miR-499a-5p. miR-499a-5p inhibited breast cancer cell growth by downregulating TMEM189. Furthermore, the down-regulation of TMEM189 promotes ferroptosis in breast cancer cells. The low expression of TMEM189 inhibited the development of breast cancer through the ferroptosis pathway. We have demonstrated for the first time that miR-499a-5p inhibits breast cancer progres­sion by targeting the TMEM189-mediated ferroptosis pathway.

Metabolic differences between colorectal cancer (CRC) and NI (NI) play an important role in early diagnoses and in-time treatments. We investigated the metabolic alterations between CRC patients and NI, and identified some potential biomarkers, and these biomarkers might be used as indicators for diagnosis of CRC. In this study, there were 79 NI, 50 CRC I patients, 52 CRC II patients, 56 CRC III patients, and 52 CRC IV patients. MS-MS was used to measure the metabolic alterations. Univariate and multivariate data analysis and metabolic pathway analysis were applied to analyze metabolic data and determine differential metabolites. These indicators revealed that amino acid and fatty acids could separate these groups. Several metabolites indicated an excellent variables capability in the separation of CRC patients and NI. Ornithine, arginine, octadecanoyl carnitine, palmitoyl carnitine, adipoyl carnitine, and butyryl carnitine/propanoyl carnitine were selected to distinguish the CRC patients and NI. And methionine and propanoyl carnitine, were directly linked to different stages of CRC. Receiver operating characteristics curves and variables importance in projection both represented an excellent performance of these metabolites. In conclusion, we assessed the difference between CRC patients and NI, which supports guidelines for an early diagnosis and effective treatment.