Identification of MAD2L1 and BUB1B as Potential Biomarkers Associated with Progression and Prognosis of Ovarian Cancer.

Ovarian cancer develops insidiously and is frequently diagnosed at advanced stages. Screening for ovarian cancer is an effective strategy for reducing mortality. This study aimed to investigate the molecular mechanisms underlying the development of ovarian cancer and identify novel tumor biomarkers for the diagnosis and prognosis of ovarian cancer. Three databases containing gene expression profiles specific to serous ovarian cancer (GSE18520, GSE12470, and GSE26712) were acquired. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were analyzed for the differentially expressed gene (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING database. The pivotal genes in the PPI network were screened using the Cytoscape software. Survival curve analysis was performed using a Kaplan-Meier Plotter. The cancer genome atlas and Gene Expression Omnibus databases were used to find the relationship between Hub gene and serous ovarian cancer. PCR and immunohistochemistry were used to detect the expression of Hub gene in serous ovarian cancer tissues and cells. Downstream pathways of the candidate tumor marker genes were predicted using Gene Set Enrichment Analysis. In this study, 252 DEGs were screened for pathway enrichment. 20 Hub genes were identified. Survival analysis suggested that Aurka, Bub1b, Cenpf, Cks1b, Kif20a, Mad2l1, Racgap1, and Ube2c were associated with the survival of patients with serous ovarian cancer. MAD2L1 and BUB1B levels were significantly different in serous ovarian cancer at different stages. Finally, Mad2l1 was found to play a role in the cell cycle, oocyte meiosis, and ubiquitin-mediated proteolysis. Meanwhile, Bub1b may play a role in the cell cycle, ubiquitin-mediated proteolysis, and spliceosome processes. Mad2l1 and Bub1b could be used as markers to predict ovarian carcinogenesis and prognosis, providing candidate targets for the diagnosis and treatment of serous ovarian cancer.

Investigating the influence of primary uterine tumor site on pelvic and para-aortic lymph node metastatic pattern and evaluating the risk factors for lymph node metastases in endometrial carcinoma: A retrospective study.

To assess the metastatic pattern in pelvic and para-aortic lymph nodes in relation with the primary uterine tumor site and to evaluate risk factors for lymph node metastases. 212 patients with endometrial cancer who underwent surgical treatment from December 2014 to December 2019 were selected. The clinical and pathological data were retrospectively analyzed. The factors and uterine primary tumor site related to lymph node metastasis were analyzed by univariate and multivariate analysis. Among the 212 patients with endometrial cancer, 17 cases had lymph node metastasis, and thus the metastasis rate was 8.02%. Univariate analysis revealed that lymph node metastasis was significantly correlated with Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, tumor size, pathological grade, and lymphovascular space invasion (P < .05) and was not correlated with age, pathological type, and cervical involvement (P > .05). Primary uterine tumor site (fundus, horns, body or lower uterine segment) with or without cervical involvement was associated with different lymph nodes' metastatic sites. The lymph node metastatic pathways of endometrial cancer mainly include obturator lymph nodes and para-aortic lymph nodes, and skip metastasis may occur; endometrial carcinoma may jump and metastasize to para-aortic lymph nodes, specially when the lesion is located in the uterine fundus and uterine horns (cornua of uterus); there is a significant correlation between the location of lymph node metastasis and the location of primary uterine malignant tumor.

Effectiveness and safety of decompression alone versus decompression plus fusion for lumbar spinal stenosis with degenerative spondylolisthesis: a systematic review and meta-analysis.

Background: There have been lingering controversies reported decompression and plus fusion. And the relative safety of fusion in addition to standard decompression remains unclear. This study aimed to assess the effectiveness and safety of decompression alone or combined with fusion in lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS). Methods: In this systematic review and meta-analysis, we searched the databases of PubMed, Embase, Cochrane Library, and Web of Science for relevant literature from their inception to 28th December 2021. We identified the eligible studies based on the PICOS principles, populations (LSS with DS), interventions (decompression alone), controls (decompression combined with fusion), outcomes [overall reoperation rate, complications, Oswestry Disability Index (ODI), operative time, the amount of blood lost, length of stay (LOS), and visual analog scales (VAS)], study design (cohort studies). Quality assessment for individual study was performed with the Newcastle-Ottawa Scale (NOS). Results: In all, 12 articles involving a total of 14,693 patients were finally included in the study, the majority of patients underwent decompression alone (DA group: n=11,598) and the rest underwent decompression associated with fusion (FU group: n=3,095). The quality of most of the included studies was regarded as high quality. The results indicated that the FU group had a higher rate of complication [relative risk (RR): 1.770, 95% confidence interval (CI): 1.485 to 2.110], longer operative time [weighted mean difference (WMD): 51.037, 95% CI: 13.743 to 88.330], and increased blood loss (WMD: 258.354, 95% CI: 150.468 to 366.239) than the DA group (all P<0.05), with no significant differences for overall reoperation rate (RR: 0.879, 95% CI: 0.432 to 1.786), ODI (WMD: -2.569, 95% CI: -6.548 to 1.409), LOS (WMD: 3.838, 95% CI: -2.172 to 9.848), and VAS found between the two groups (P>0.05). Conclusions: In patients with LSS + DS, the effectiveness and safety of decompression alone may be superior to decompression plus fusion in terms of complication rate, operative time, and the amount of bleeding. However, more high-quality literature is needed in the future to confirm the best treatment choice for patients with LSS + DS.

Drug Discovery Inspired from Nuclear Receptor Sensing of Microbial Signals.

Host-microbiota interactions are vital for diverse pathophysiological events and may be targeted for innovative therapeutics. Nuclear receptors (NRs) are versatile host sensors of microbial signals that coordinate diverse environmental cues with local and remote adaptions. Harnessing NR-mediated sensory machinery could provide an alternative lynchpin for gut microbiota-oriented drug discovery strategy.

A diet-microbial metabolism feedforward loop modulates intestinal stem cell renewal in the stressed gut.

Dietary patterns and psychosocial factors, ubiquitous part of modern lifestyle, critically shape the gut microbiota and human health. However, it remains obscure how dietary and psychosocial inputs coordinately modulate the gut microbiota and host impact. Here, we show that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells (ISC) renewal and epithelial homeostasis. Chow diet (CD) and purified diet (PD) confer distinct vulnerability to gut epithelial injury, microbial alternation and ISC dysfunction in chronically restrained mice. CD preferably enriches Lactobacillus reuteri, and its colonization is sufficient to rescue stress-triggered epithelial injury. Mechanistically, dietary raffinose sustains Lactobacillus reuteri growth, which in turn metabolizes raffinose to fructose and thereby constituting a feedforward metabolic loop favoring ISC maintenance during stress. Fructose augments and engages glycolysis to fuel ISC proliferation. Our data reveal a diet-stress interplay that dictates microbial metabolism-shaped ISC turnover and is exploitable for alleviating gut disorders.

Evaluation of cervical length and optimal timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia: A retrospective study.

To evaluate the change of cervical length and the best timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia (CIN).This was a retrospective study including patients under 40 years with fertility desire treated by cervical conization for CIN. To assess the cervical length, the patients were divided into 2 groups according to different surgery procedure: loop electrosurgical excision procedure (LEEP) and cold knife conisation (CKC). Patients with cervical length < 2.5 cm in CKC group were divided into 2 groups according to whether receiving cervical cerclage. Trans-vaginal ultrasound examination was used to measure cervical length by fixed professional sonographers.In LEEP group, the cervical length preoperative was significantly longer than 3 months postoperatively (3.03 ±â€Š0.45 cm vs 2.84 ±â€Š0.44 cm, P = .000). In CKC group, the cervical length preoperative was significantly longer than 3 and 6 months postoperatively (2.90 ±â€Š0.41 cm vs 2.43 ±â€Š0.43 cm and 2.68 ±â€Š0.41 cm, respectively, P = .000). Cervical length was significantly longer at 12 and 9 months after cerclage compared to that without cerclage. Eighteen patients got pregnant in LEEP group, among which one was pregnant at 5 months postoperatively and had premature delivery. There was 1 inevitable abortion and 1 preterm birth among 39 pregnant patients from CKC group.Patients who have fertility desire with CIN were recommended for pregnancy at 6 and 9 months after LEEP and CKC, respectively. Cerclage effectively prolonged cervical length in patents with that less than 2.5 cm to prevent cervical incompetence.

Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice.

BACKGROUND: Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear. HYPOTHESIS/PURPOSE: Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component. METHODS: Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed. RESULTS: TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP. CONCLUSION: Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.

Changes of Intestinal Microbiota in Ovarian Cancer Patients Treated with Surgery and Chemotherapy.

PURPOSE: Ovarian cancer is the leading cause of death in gynecologic malignancies. Growing evidences demonstrate that a complicated relationship exists between the gut microbiota and cancer treatment. However, there are few studies explored the alterations of gut microbiota in ovarian cancer patients following anti-cancer treatments. Therefore, we aim to analyze the changes of the gut microbiota in ovarian cancer patients treated with radical surgery and chemotherapy. PATIENTS AND METHODS: The microbial genes were examined from a total of 75 fecal samples from 18 ovarian cancer patients, including 10 preoperative fecal samples (Group B), 4 postoperative fecal samples (Group M0), as well as 61 fecal samples after first to fifth cycles of chemotherapy, using 16S rRNA sequencing. RESULTS: Our results showed that fecal samples collected in postoperative (Group M0) exhibited significant decreases in abundance of Bacteroidetes and Firmicutes, while a significant increase in abundance of Proteobacteria compared with preoperative (Group B) fecal samples. LEfSe analysis identified that Bilophila and Faecalibacterium are the key genera in Group B, while Klebsiella and Enterococcus are the key genus in Group M0. Compared with before chemotherapy, the abundance of Bacteroidetes and Firmicutes increased, and the abundance of Proteobacteria decreased after chemotherapy. In addition, anaerobic bacteria, such as Bacteroides, Collinsella and Blautia, exhibited significant increases after chemotherapy. Moreover, we observed that certain bacterial genera were significantly correlated with clinicopathological characteristics of ovarian cancer patients. CONCLUSION: Our study suggested that radical surgery and chemotherapy altered the composition of gut microbiota in ovarian cancer patients. Therapeutic strategies targeting the gut microbiota may be beneficial for the clinical treatment of ovarian cancer.

WTAP is a prognostic marker of high-grade serous ovarian cancer and regulates the progression of ovarian cancer cells.

BACKGROUND: The Wilms' tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism. MATERIALS AND METHODS: To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus. RESULTS: High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival (P<0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group (P<0.01), benign ovarian tumor group (P<0.01), and non-HGSOC group (P<0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis (P<0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways. CONCLUSION: WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.

Kynurenic acid/GPR35 axis restricts NLRP3 inflammasome activation and exacerbates colitis in mice with social stress.

Psychological stress is well known to increase colitis susceptibility and promote relapse. Metabolic changes are commonly observed under psychological stress, but little is known how this relates to the progression of colitis. Here we show that kynurenic acid (KA) is an endogenous driver of social stress-exacerbated colitis via regulating the magnitude of NLRP3 inflammasome. Chronic social defeat stress (CSDS) in mice induced colonic accumulation of KA, and mice receiving KA during CSDS had defects in colonic NLRP3 inflammasome activation. Mechanistically, KA activated GPR35 signaling to induce autophagy-dependent degradation of NLRP3 in macrophages, thereby suppressing IL-1ß production. Socially defeated mice with KA treatment displayed enhanced vulnerability to subsequent dextran sulphate sodium (DSS)-induced colonic injury and inflammatory disturbance, and this effect was reversed by autophagic inhibition that blocked the NLRP3-suppressive effect of KA. Thus, our research describes a mechanism by which KA/GPR35 signaling represses adaptive NLRP3 inflammasome activation to increase colitis susceptibility and suggests a potential metabolic target for the intervention of stress-related colonic disorder.

The complete mitochondrial genome sequence of the budgerigar, Melopsittacus undulatus.

Here, we describe the budgie's mitochondrial genome sequence, a resource that can facilitate this parrot's use as a model organism as well as for determining its phylogenetic relatedness to other parrots/Psittaciformes. The estimated total length of the sequence was 18,193 bp. In addition to the to the 13 protein and tRNA and rRNA coding regions, the sequence also includes a duplicated hypervariable region, a feature unique to only a few birds. The two hypervariable regions shared a sequence identity of about 86%.

Screening for genes involved in antibody response to sheep red blood cells in the chicken, Gallus gallus.

Antibody response, an important trait in both agriculture and biomedicine, plays a part in protecting animals from infection. Dissecting molecular basis of antibody response may improve artificial selection for natural disease resistance in livestock and poultry. A number of genetic markers associated with antibody response have been identified in the chicken and mouse by linkage-based association studies, which only define genomic regions by genetic markers but do not pinpoint genes for antibody response. In contrast, global expression profiling has been applied to define the molecular bases of a variety of biological traits through identification of differentially expressed genes (DEGs). Here, we employed Affimetrix GeneChip Chicken Genome Arrays to identify differentially expressed genes for antibody response to sheep red blood cells (SRBC) using chickens challenged with and without SRBC or chickens with high and low anti-SRBC titers. The DEGs include those with known (i.e., MHC class I and IgH genes) or unknown function in antibody response. Classification test of these genes suggested that the response of the chicken to intravenous injection of SRBC involved multiple biological processes, including response to stress or other different stimuli, sugar, carbohydrate or protein binding, and cell or soluble fraction, in addition to antibody response. This preliminary study thus provides an insight into molecular basis of antibody response to SRBC in the chicken.

Mitochondrial DNA-Based Analyses of Relatedness Among Turkeys, Meleagris gallopavo.

The domesticated turkey, Meleagris gallopavo, is believed to be a single breed with several varieties whose relatedness and origins remain poorly understood. Using the mitochondrial genome sequence (GenBank accession no. EF153719) that our group first reported, we investigated the relationships among 15 of the most widely occurring turkey varieties using D-loop and 16S RNA sequences. We included, as a non-traditional outgroup, mtDNA sequence information from wild turkey varieties. A total of 24 SNPs, including 18 in the D-loop and 6 in the 16S rRNA, was identified, validated and used. Of the 15 haplotypes detected based on these SNPs, 7 were unique to wild turkeys. Nucleotide diversity estimates were relatively low when compared to those reported for chickens and other livestock. Network and phylogenetic analyses showed a closer relationship among heritage varieties than between heritage and wild turkeys. The mtDNA data provide additional evidence that suggest a recent divergence of turkey varieties.

[Distribution and regulation of Panx1 protein].

Pannexin1 (Panx1) is a subtype of the newly discovered gap junction proteins named Pannexin(s). Panx1 is widely expressed in the nervous system, cardiovascular system, etc and can form non-selective and large conductance hemichannel. It has been demonstrated that various conditions can regulate Panx1 open and affect the body's physiological function via macromolecular substance (for instance, ATP) releasing. This review gives a detailed introduction to the main distribution of Panxl, summarizes the open and inhibition condition of Panx1, and finally, prospects directions of future research.

Mitochondrial DNA sequence and haplotype variation analysis in the chicken (Gallus gallus).

Although it is known to be useful for certain genotype:phenotype assignments, our knowledge of the nature and extent of variation in the entire chicken (Gallus gallus) mitochondrial genome (mtGenome) is limited. Here, we used experimental and in silico tools to identify nucleotide variants in the mtGenome, including the coding and non-coding (D-loop) regions. The distribution of the experimentally identified mitochondrial DNA variants in meat- (broilers) and egg-type (White Leghorn) chickens was also assessed. A total of 113 single-nucleotide polymorphisms (SNPs) were identified. The in silico analysis revealed a total of 91 SNPs, with 70 in the coding region and 21 in the non-coding region. Of the 41 experimentally identified SNPs, 27 were in the D-loop. Together, the experimentally identified SNPs in the non-coding region formed 11 haplotypes, whereas the 14 SNPs in the coding region formed 6. Though, 9 of the D-loop region haplotypes were observed only in broilers, 3 of the 6 haplotypes from the coding region occurred at a significantly higher frequency in broilers. To our knowledge, this investigation represents the first whole-mtGenome scan for variation and an evaluation, though limited in sample size, of the haplotype distribution in meat- and egg-type populations, using the SNPs and haplotypes identified.

[Molecular genetic diversity of phytoplankton rbcL gene in Jiaozhou Bay].

The variants of a 500 base pair fragment of RubisCo large subunit gene (rbcL) from the phytoplanktonic DNA of Jiaozhou Bay surface seawater were amplified by using polymerase chain reaction and cloned. Twenty-eight clones were randomly selected and sequenced, which were further used to determine the molecular genetic diversity of the phytoplankton of Jiaozhou Bay surface seawater. Systematic analysis showed that the clones representing cryptophyta counted for 28.6%, Stramenopiles 32.1%, Haptophyta 28.6%, Rhodophyta 3.6% and Chlorophyta 7.1%. The sequences from Cryptophyta, Stramenopiles, Haptophyta and Rhodophyta belonged to type D of Form I rbcL and Chlorophyta to type B, indicating that the dominant phytoplankton were those represented by type D rbcL. The genetic diversity index and the reversely translated amino acid sequence diversity of Jiaozhou Bay phytoplankton were 2.85 and 0.20, which were determined by the abundances of operational taxonomy units and the reversely translated amino acid sequences respectively.