The molecular characteristic analysis of TRIB2 gene and its expressional patterns in Bos grunniens tissue and granulosa cells.

Tribbles homolog 2 (TRIB2) plays an important role in the follicular development of female mammals. However, its expression and function in the yak (Bos grunniens) are still unclear. In this study, we predicted the molecular characteristics of TRIB2, and revealed its expression pattern in yak (Bos grunniens) tissues and ovarian granulosa cells. We cloned the full length of the yak TRIB2 gene obtained by RT-PCR was 1368 bp and the coding sequence (CDS) was 624 bp, encoding 207 amino acids (AA). Homology analysis showed that the yak TRIB2 is highly conserved among species. TRIB2 was detected to be extensively expressed in seven tissues of the yak liver, spleen, lung, kidney, ovary, oviduct and uterus by qPCR. The expression of TRIB2 mRNA in the ovary during gestation was significantly lower than that in the non-pregnant (p < 0.05). At each stage of follicle development, the TRIB2 mRNA in granulosa cells showed a significant upward trend with the development of follicles. The expression of TRIB2 gradually decreased with the increase of the culture time of the granulosa cells in vitro. In conclusion, these results suggest that TRIB2 may play an important role in the follicular development of yaks.

Local resection versus radical resection for early-stage rectal cancer: a systematic review and meta-analysis.

PURPOSE: The optimal surgical approach for early-stage rectal cancer remains controversial. Radical resection is considered to be the gold standard for rectal cancer treatment. More and more studies show that local resection can replace traditional radical resection in the treatment of early rectal cancer. This research aimed to compare the efficacy of local excision and radical surgery for early-stage rectal cancer and report the evidence-based clinical advantages of both techniques. METHODS: The clinical trials comparing oncological and perioperative local and radical resection outcomes for early-stage rectal cancer were searched from 7 national and international databases. RESULTS: Finally, 3 randomized controlled trials and 14 cohort studies were included. In terms of oncology and perioperative outcomes, there were no statistically significant differences between the radical resection group and the local resection group in terms of OS (HR = 1.05, 95% CI (0.98, 1.13), DFS [HR = 1.18, 95% CI (0.93, 1.48), p = 0.168), distant metastasis rate (RR = 1.04, 95% CI (0.49, 2.20), p = 0.928), and mortality rate (RR = 1.52, 95% CI (0.80, 2.91), p = 0.200). However, there were significant differences in the outcomes of complications (RR = 2.85, 95% CI (2.07, 3.92), p < 0.001), length of hospital stays (WMD = 5.41, 95% CI (3.94, 6.87), p < 0.001), stoma rate (RR = 7.69, 95% CI (2.39, 24.77), p = 0.001), local recurrence rate (RR = 0.48, 95% CI (0.27, 0.86), p = 0.013), operative time (WMD = 74.68, 95% CI (68.00, 81.36), p < 0.001), blood loss (WMD = 156.36, 95% CI (95.48, 217.21, p < 0.001), and adverse events (RR = 1.59, 95% CI (1.05, 2.41), p = 0.027). CONCLUSION: Local excision may be a viable alternative to radical resection for early-stage rectal cancer, but higher quality clinical studies are needed to confirm this.

Risk and incidence of colorectal stricture progressing to colorectal neoplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

This study aims to assess the risk of colorectal stricture progressing to colorectal neoplasia (CRN) in patients with inflammatory bowel disease (IBD). The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the date of databases' creation to 5 November 2022. The Newcastle-Ottawa Scale was used to evaluate the quality of the included literature. Meta-analysis was conducted using the Stata 15 software and R 4.04 software. Two case-control studies and 12 cohort studies were eventually included. Colorectal stricture in patients with IBD increased the risk of progressing to CRN [odds ratio (OR): 1.52, 95% confidence interval (CI): 1.02-2.29, P = 0.042], but was irrelevant to the risk of progressing to ACRN (OR: 3.56, 95% CI 0.56-22.70, P = 0.180). The risk of CRN were further distinguished in patients with ulcerative colitis (UC) and Crohn's disease (CD) Our findings showed that colorectal stricture may increase the risk of progressing to CRN in patients with UC (OR = 3.53, 95%CI 1.62-7.68, P = 0.001), but was irrelevant to the risk of progressing to CRN in patients with CD (OR = 1.09, 95% CI 0.54-2.21, P = 0.811). In conclusion, colorectal stricture in patients with IBD can be used as a risk factor for predicting CRN but cannot be used as a risk factor for predicting ACRN. Stricture is a risk factor for CRN in patients with UC but not in patients with CD. More prospective, multi-center studies with large samples are expected to confirm our findings.

Comparative Genomic Analysis of the Thiolase Family and Functional Characterization of the Acetyl-Coenzyme A Acyltransferase-1 Gene for Milk Biosynthesis and Production of Buffalo and Cattle.

Cattle and buffalo served as the first and second largest dairy animals, respectively, providing 96% milk products worldwide. Understanding the mechanisms underlying milk synthesis is critical to develop the technique to improve milk production. Thiolases, also known as acetyl-coenzyme A acetyltransferases (ACAT), are an enzyme family that plays vital roles in lipid metabolism, including ACAT1, ACAT2, ACAA1, ACAA2, and HADHB. Our present study showed that these five members were orthologous in six livestock species including buffalo and cattle. Transcriptomic data analyses derived from different lactations stages showed that ACAA1 displayed different expression patterns between buffalo and cattle. Immunohistochemistry staining revealed that ACAA1 were dominantly located in the mammary epithelial cells of these two dairy animals. Knockdown of ACAA1 inhibited mammary epithelial cell proliferation and triglyceride and ß-casein secretion by regulating related gene expressions in cattle and buffalo. In contrast, ACAA1 overexpression promoted cell proliferation and triglyceride secretion. Finally, three novel SNPs (g.-681A>T, g.-23117C>T, and g.-24348G>T) were detected and showed significant association with milk production traits of Mediterranean buffaloes. In addition, g.-681A>T mutation located in the promoter region changed transcriptional activity significantly. Our findings suggested that ACAA1 play a key role in regulating buffalo and cattle milk synthesis and provided basic information to further understand the dairy animal lactation physiology.

WDHD1 is over-expressed in nasopharyngeal carcinoma and may control the expression of ITGAV.

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.

FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.

Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility.

Clinical value and potential mechanisms of BUB1B up-regulation in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) has insidious onset, late clinical diagnosis and high recurrence rate, which leads to poor quality of patient life. Therefore, it is necessary to further explore the pathogenesis and therapy targets of NPC. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) was found to be up-regulated in a variety of cancers, but only two previous study showed that BUB1B was overexpressed in NPC and the sample size was small. The clinical role of BUB1B expression and its underlying mechanism in NPC require more in-depth research. Immunohistochemical samples and public RNA-seq data indicated that BUB1B protein and mRNA expression levels were up-regulated in NPC, and summary receiver operating characteristic curve indicated that BUB1B expression level had a strong ability to distinguish NPC tissues from non-NPC tissues. Gene ontology and Kyoto Encyclopedia of genes and genomes were performed and revealed that BUB1B and its related genes were mainly involved in cell cycle and DNA replication. Protein- Protein Interaction were built to interpret the BUB1B molecular mechanism. Histone deacetylase 2 (HDAC2) could be the upstream regulation factor of BUB1B, which was verified by Chromatin Immunoprecipitation Sequencing samples. In summary, BUB1B was highly expressed in NPC, and HDAC2 may affect cell cycle by regulating BUB1B to promote cancer progression.

The clinical significance of transcription factor WD repeat and HMG-box DNA binding protein 1 in laryngeal squamous cell carcinoma and its potential molecular mechanism.

BACKGROUND: Currently, high expression of WD repeat and HMG-box DNA binding protein 1 (WDHD1) has been found in a variety of tumors; but there is no research has been conducted concerning the expression of WDHD1 in laryngeal squamous cell carcinoma (LSCC). Our purpose is to investigate the expression and the latent mechanism of WDHD1 in LSCC. METHODS: Firstly, 9 data sets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and ArrayExpress were statistically analyzed to explore the expression of WDHD1 in LSCC; immunohistochemistry was performed in 79 LSCC tissues and 44 non-cancer tissues to further verify the result. In addition, the target gene of WDHD1 was predicted and immunohistochemistry was used to detect the expression of the target gene. The potential mechanism of WDHD1 in LSCC was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and protein-protein interaction network (PPI). RESULTS: The WDHD1 mRNA was expressed at higher levels in the LSCC tissue than in the normal tissue (SMD=1.90, 95% CI=1.50-2.30); and the results of immunohistochemistry were consistent with the conclusion. Using chip-seq analysis, we found that S-phase kinase-associated protein 2 (Skp2) had a significant binding peak with WDHD1, and the expression of these two genes was significantly positively correlated. Immunohistochemistry showed that Skp2 was also highly expressed in LSCC. In addition, GO and KEGG analysis revealed the WDHD1 positively correlated genes was closely related to cell cycle, and PPI analysis identified 10 hub genes: COL7A1, COL4A2, COL4A1, COL4A6, COL11A1, COL5A2, COL1A1, COL13A1, COL8A1 and COL10A1, which may be critical to the progression of LSCC. CONCLUSIONS: WDHD1 was overexpressed in LSCC tissues. Meanwhile, WDHD1 and its target gene Skp2 for transcriptional regulation may play a role in the progression of LSCC by regulating the cell cycle.

Effectiveness of arthroscopic management of idiopathic shoulder stiffness: A meta-analysis.

BACKGROUND: Persisting shoulder stiffness adversely affects quality of life by causing pain and motion restrictions especially in patients with diabetes. OBJECTIVE: The aim of this study was to evaluate the outcomes of arthroscopic capsular release in patients with idiopathic shoulder stiffness. METHOD: A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. Random-effects meta-analyses were performed to estimate the changes at latest follow-up in scores of the Constant, American Shoulder and Elbow Surgeons (ASES), and University of California at Los Angelis (UCLA) scales, Visual Analogue Scale (VAS), and shoulder range of motion. RESULTS: Nineteen studies were included. The follow-up duration was 42 months [95% confidence interval (CI): 32, 51]. Improvements in scores of the Constant, ASES, UCLA scales, and VAS were 48.3 [95% CI: 38.0, 58.6], 44.6 [95% CI: 24.6, 64.6], 19.3 [95% CI: 16.6, 22.0], and -6.1 [95% CI: -6.9, -5.4] respectively (P< 0.05 all). Improvements in the shoulder range of motion were: abduction 82.0 [95% CI: 65.0, 98.9]; forward flexion 75.9 [95% CI: 59.7, 92.1]; external rotation 43.2 [95% CI: 37.5, 49.0]; and internal rotation 25.4 [95% CI: 15.2, 35.5] degrees; P< 0.05 all). CONCLUSION: Arthroscopic capsular release effectively improves shoulder function in patients with idiopathic shoulder stiffness.

The Potential Value of Targeting Ferroptosis in Early Brain Injury After Acute CNS Disease.

Acute central nervous system (CNS) disease is very common and with high mortality. Many basic studies have confirmed the molecular mechanism of early brain injury (EBI) after acute CNS disease. Neuron death and dysfunction are important reasons for the neurological dysfunction in patients with acute CNS disease. Ferroptosis is a nonapoptotic form of cell death, the classical characteristic of which is based on the iron-dependent accumulation of toxic lipid reactive oxygen species. Previous studies have indicated that this mechanism is critical in the cell death events observed in many diseases, including cancer, tumor resistance, Alzheimer's disease, Parkinson's disease, stroke, and intracerebral hemorrhage (ICH). Ferroptosis may also play a very important role in EBI after acute CNS disease. Unresolved issues include the relationship between ferroptosis and other forms of cell death after acute CNS disease, the specific molecular mechanisms of EBI, the strategies to activate or inhibit ferroptosis to achieve desirable attenuation of EBI, and the need to find new molecular markers of ferroptosis that can be used to detect and study this process in vivo after acute CNS disease.

Hydrogen sulfide prevents OGD/R-induced apoptosis via improving mitochondrial dysfunction and suppressing an ROS-mediated caspase-3 pathway in cortical neurons.

Hydrogen sulfide (H2S), an endogenous gaseous mediator, has been shown to have protective effects against neuronal damage caused by brain ischemia. In this study, we explored the potential effects of H2S on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal apoptosis and the possible mechanisms. We find that sodium hydrosulfide (NaHS, a donator of H2S) prevents OGD/R-induced intracellular reactive oxygen species (ROS) elevation and activation of caspase-3 in cultured mouse cortical neurons. The pretreatment of N-acetyl-l-cysteine (NAC, an ROS scavenger) also prevents OGD/R-induced activation of caspase-3. Both NaHS and NAC counteract OGD/R-induced decline in mitochondria membrane potential (MMP). Additionally, NaHS, NAC or N-Acetyl-Asp-Glu-Val-Asp-CHO (DEVD-CHO, a caspase-3 inhibitor), is shown to significantly inhibit OGD/R-induced neuronal apoptosis. These data suggest that H2S can protect against OGD/R-induced neuronal apoptosis through improving mitochondria dysfunction and suppressing an ROS-activated caspase-3 signaling pathway.