Organoids: new frontiers in tumor immune microenvironment research.

The tumor microenvironment (TME) contains cells that regulate medication response and cancer growth in a major way. Tumor immunology research has been rejuvenated and cancer treatment has been changed by immunotherapy, a rapidly developing therapeutic approach. The growth patterns of tumor cells in vivo and the heterogeneity, complexity, and individuality of tumors produced from patients are not reflected in traditional two-dimensional tumor cell profiles. On the other hand, an in vitro three-dimensional (3D) model called the organoid model is gaining popularity. It can replicate the physiological and pathological properties of the original tissues in vivo. Tumor cells are the source of immune organoids. The TME characteristics can be preserved while preserving the variety of tumors by cultivating epithelial tumor cells with various stromal and immunological components. In addition to having genetic and physical similarities to human diseases and the ability to partially reconstruct the complex structure of tumors, these models are now widely used in research fields including cancer, developmental biology, regenerative mechanisms, drug development, disease modeling, and organ transplantation. This study reviews the function of organoids in immunotherapy and the tumor immune milieu. We also discuss current developments and suggest translational uses of tumor organoids in immuno-oncology research, immunotherapy modeling, and precision medicine.

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Advances and Applications of Cancer Organoids in Drug Screening and Personalized Medicine.

In recent years, the rapid emergence of 3D organoid technology has garnered significant attention from researchers. These miniature models accurately replicate the structure and function of human tissues and organs, offering more physiologically relevant platforms for cancer research. These intricate 3D structures not only serve as promising models for studying human cancer, but also significantly contribute to the advancement of various potential applications in the field of cancer research. To date, organoids have been efficiently constructed from both normal and malignant tissues originating from patients. Using such bioengineering platforms, simulations of infections and cancer processes, mutations and carcinogenesis can be achieved, and organoid technology is also expected to facilitate drug testing and personalized therapies. In conclusion, regenerative medicine has the potential to enhance organoid technology and current transplantation treatments by utilizing genetically identical healthy organoids as substitutes for irreversibly deteriorating diseased organs. This review explored the evolution of cancer organoids and emphasized the significant role these models play in fundamental research and the advancement of personalized medicine in oncology.

Ability of the European League Against Rheumatism-Outcomes Measures in Rheumatology combined scoring system for grading dorsal joint space synovitis to accurately evaluate ultrasound-detected hand synovitis.

Background: The European League Against Rheumatism-Outcomes Measures in Rheumatology (EULAR-OMERACT) recommend only scanning dorsal spaces for scoring ultrasound-detected hand synovitis. This study evaluated the efficiency of the combined scoring system only depending on dorsal joint spaces synovitis in diagnosing and evaluating ultrasound-detected hand synovitis. Methods: The data of 56 patients who underwent hand joint ultrasonography exams in the Ultrasound Department of West China Hospital, Sichuan University were prospectively collected. The participants formed a random series. The images of each patient included gray-scale (GS) and power Doppler (PD) images of bilateral first to fifth metacarpophalangeal joints (MCP) and the thumb and second to fifth proximal interphalangeal joints (IP). The synovial thickness was measured quantitatively in GS images, and the synovial GS scores in the dorsal joint spaces and PD scores in the dorsal and volar joint spaces were calculated according to the combined EULAR-OMERACT scoring system. Results: The detection rate of synovitis in the first to fifth MCP, thumb and second to fifth proximal IP synovitis were 41.4% (232/560) and 33.9% (190/560), respectively. The sensitivity of only inspecting the dorsal joint spaces with GS ultrasound was 79.3% for MCP and 52.6% for the thumb and second to fifth proximal IPs. The PD scores were higher in the dorsal joint spaces than in the volar joint spaces (P value <0.001). The combined scores were higher than either the GS or PD scores alone in the dorsal joint spaces (P value of the combined scores vs. GS scores =0.001; P value of the combined scores vs. PD scores <0.001). Conclusions: Adopting the EULAR-OMERACT combined scoring standard is recommended to evaluate ultrasound-detected hand synovitis, as determined by the highest value of the GS scores or the PD scores. More specifically, PD scores can mainly be used to appraise the dorsal joint spaces. However, GS scores should be used to evaluate both the dorsal joint spaces and the volar joint spaces.

Renal functional outcomes after nephrectomy in patients with localized renal cell carcinoma and diabetes mellitus: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Diabetes mellitus (DM), one of the most common comorbidities in patients with renal cell carcinoma (RCC), was proven to be an important prognostic factor of overall survival for these patients. Regarding the influence on renal function after nephrectomy, evidence is still scant. This systematic review and meta-analysis was conducted to provide a more reliable analysis of the association between DM and long-term renal functional outcomes after nephrectomy. METHODS: The PubMed, Web of Science, Embase and Cochrane Library (CENTRAL) databases were searched for eligible studies from inception to January 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate the association between DM and renal functional outcomes using a random effects model. Stata 17.0 software was used for statistical analysis. RESULTS: The meta-analysis included thirteen studies consisting of 8562 RCC patients who underwent nephrectomy. Preoperative comorbidity of DM was significantly associated with poor renal functional outcomes (HR = 1.91, 95% CI 1.48-2.48, p < 0.0001), regardless of ethnicity, follow-up time, body mass index (BMI) and age. However, in the radical nephrectomy subgroup, DM was not significantly associated with renal function decline (HR = 1.91, 95% CI 0.93-3.90, p = 0.0781). CONCLUSIONS: The aggregate evidence indicated that preexisting DM may be associated with poor renal functional outcomes in patients with RCC after nephrectomy, especially in patients receiving partial nephrectomy. Urologists should focus more on the glycemic management of these patients after nephrectomy. More high-quality studies are needed to explore the influence of DM on renal function outcomes in postoperative patients.

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival.

BACKGROUND: Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. METHODS: Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004-2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. RESULTS: The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. CONCLUSION: MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required.

Predicting recurrent laryngeal nerve invasion by preoperative ultrasonography in patients with thyroid carcinoma.

Background: For thyroid cancer staging, evaluation of extent of local invasion, including recurrent laryngeal nerve (RLN), may assist surgical decision-making. Methods: This prospective study evaluated patients who underwent thyroidectomy at a single tertiary-level academic institution. Patients with complete clinical information and ultrasound imaging of thyroid carcinoma and RLN were enrolled. Those who had thyroidectomy before or did not fit the above conditions were excluded. Patients were assigned to either a development or validation cohort. Development of models was constructed in a primary cohort based on preoperative ultrasound features and clinicodemographic data from August 2020 to December 2021. Validation of the models was then performed on an independent cohort between January and March of 2022. Multivariate logistic regression and nomograms were mainly used for statistical analysis. Results: Using data from 816 patients (80 RLN invasion), we built nomogram 1 based on age [95% confidence interval (CI): 1.315 to 145.933, P=0.029], body mass index (BMI; 95% CI: 1.228 to 10.874, P=0.020), tumor size (95% CI: 4.677 to 1,373.1, P=0.002), tumor adjacent to medial (95% CI: 1.816 to 26.713, P=0.005) and posterior thyroid capsules (95% CI: 5.567 to 756.583, P=0.001), and distance <1 mm between tumor and the RLN (95% CI: 10.389 to 826.746, P<0.001). Nomogram 2 was built based on tumor adjacent to the posterior thyroid capsule (95% CI: 2.922 to 53,074.51, P=0.017), distance <1 mm between tumor and the RLN (95% CI: 1.478 to 1,241.646, P=0.029), and loss of typical fascicular echotexture of the RLN along the long axis (95% CI: 35.11 to 53,272.81, P<0.001). In the validation cohort, nomogram 1 and 2 showed sensitivities of 94.74% and 57.89%, specificities of 74.12% and 95.29%, positive predictive values (PPV) of 45.00% and 73.26%, negative predictive values (NPV) of 98.43% and 91.03%, accuracies of 76.92% and 88.46%, and C-indices of 0.86 and 0.89. Conclusions: Preoperative ultrasound is a feasible approach to evaluate RLN invasion in patients with thyroid carcinoma. Nomogram 1 may sensitively identify the risk of RLN invasion, and it may be checked using the more specific and accurate nomogram 2 to reduce false positives.

Shear wave elastography-based skin assessment system for systemic sclerosis: a supplement or alternative to conventional ultrasound?

Background: Although shear wave elastography (SWE) has been found to have the potential to evaluate skin lesions in systemic sclerosis (SSc), current research fails to answer the following questions: (I) can high-frequency ultrasound (HFUS) and SWE at multiple sites throughout the body distinguish SSc subtypes; (II) is HFUS and SWE at every site equally affected by clinical characteristics; and (III) is SWE a supplement or a choice to HFUS. This prospective study aimed to compare the value of SWE-based skin stiffness and HFUS-based skin thickness in distinguishing different SSc subtypes, verify the influence of clinical features on SWE and HFUS, and provide a basis for the screening of the optimal evaluation sites and indicators in the future. Methods: Forty-nine limited and 51 diffuse SSc patients were included in this study. Their skin was assessed at 17 sites by palpation using the modified Rodnan skin score (mRSS), skin thickness measured by HFUS, and skin stiffness by SWE. Clinical features, including age, sex, body mass index, and disease duration, were collected. Results: The diffuse SSc patients had higher skin stiffness at most sites (P<0.05), except for the finger, foot, and forehead, and a thicker skin layer at most sites (P<0.05), except for the finger. The area under the curve (AUC) of HFUS, SWE, and the combination of the two in distinguishing diffused and limited SSc were 0.866, 0.921, and 0.973, respectively. The differences were statistically significant (combination vs. SWE, P=0.002, combination vs. HFUS, P=0.021). Longer disease duration was associated with a thinner skin layer at the forearm, arm, chest wall, abdominal wall, and thigh in limited SSc, including the leg in diffused SSc. SWE was less affected by clinical features than HFUS. SWE could achieve greater discrimination between different mRSSs at multiple sites, such as fingers and arms, than HFUS. Conclusion: For the assessment of SSc skin, SWE has several advantages over HFUS, including less influence by clinical features and greater sensitivity to discriminate different mRSSs. SWE has the potential to become a primary imaging assessment tool as well as HFUS.

Prognostic value of the pretreatment systemic immune-inflammation index in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The systemic immune-inflammation index (SII) is a novel biomarker to predict the prognosis of some malignant tumors based on neutrophil, platelet, and lymphocyte counts. Evidence is scarce about the prognostic value of SII for prostate cancer patients. This systematic review and meta-analysis was conducted to explore the prognostic value of the SII in prostate cancer. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases were searched to determine eligible studies from inception to August 15, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to pool the results. Statistical analyses were conducted by using Stata 17.0 software. RESULTS: A total of 12 studies with 8083 patients were included. The quantitative synthesis showed that a high SII was related to poor overall survival (OS) (HR = 1.44, 95% CI 1.23-1.69, p < 0.001). Furthermore, a subgroup analysis showed that a high SII was associated with poor OS in the groups of any ethnicity, tumor type, and cutoff value. An increased SII was also associated with inferior progression-free survival (PFS) (HR = 1.80, 95% CI 1.27-2.56, p = 0.001). In the subgroup analysis, a high SII value was related to poor PFS in Asian patients (HR = 4.03, 95% CI 1.07-15.17, p = 0.04) and a cutoff value > 580 (HR = 1.19, 95% CI 1.04-1.36, p = 0.01). CONCLUSION: Based on the current evidence, a high pretreatment SII may be associated with poor OS and PFS. The SII may serve as an important prognostic indicator in patients with prostate cancer. More rigorously designed studies are needed to explore the SII and the prognosis of prostate cancer.

Efficacy of LR-5 and LR-4/5 by Liver Imaging Reporting and Data System (MRI) for hepatocellular carcinoma: A meta-analysis.

To comprehensive investigate the diagnostic efficacy of LR-5 and LR-4/5 by MRI LI-RADS of suspected liver nodules. A comprehensive search of authenticated international databases including PubMed/Medline, Ovid, Embase, Web of Science as well as a series of nation-level databases, including China National Knowledge Infrastructure was carried out to look for related studies with respect to the diagnostic performance of MRI LR-5 or LR-4/5 for HCC. Subsequently, main data including the basic information of the articles incorporated as well as main outcomes, including diagnostic sensitivity, specificity, accuracy, or original data like true positive, false positive, true negative and false negative values were extracted. Next, forest plots were generated to reveal the pooled diagnostic sensitivity, specificity. The diagnostic sensitivity, specificity of LR-5 and LR-4/5 by LI-RADS were comparatively satisfactory. The pooled diagnostic sensitivity and specificity of MRI LR-5 with respect to pathologically diagnosed HCC were 0.73 [95% CI 0.7-0.75] and 0.88 [95% CI 0.86-0.90] respectively. The pooled sensitivity and specificity of MRI LR-4/5 were 0.77 [95% CI 0.75-0.80] and 0.82 [95% CI 0.79-0.85] respectively. Through this systematic review and meta-analysis, we found a promisingly satisfactory diagnostic efficacy of LR-5 and LR-4/5 by MRI LI-RADS of suspected malignant liver nodules, manifested by optimal diagnostic sensitivity, specificity, and accuracy.

Poor prognosis, hypomethylation, and immune infiltrates are associated with downregulation of INMT in head and neck squamous cell carcinoma.

Background: Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time. Methods: Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB. Results: In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels. Conclusion: HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.

Feminization of channel catfish with 17ß-oestradiol involves methylation and expression of a specific set of genes independent of the sex determination region.

Exogenous oestrogen 17ß-oestradiol (E2) has been shown to effectively induce feminization in teleosts. However, the molecular mechanisms underlying the process remain unclear. Here, we determined global DNA methylation and gene expression profiles of channel catfish (Ictalurus punctatus) during early sex differentiation after E2 treatment. Overall, the levels of global DNA methylation after E2 treatment were not significantly different from those of controls. However, a specific set of genes were differentially methylated, which included many sex differentiation-related pathways, such as MARK signalling, adrenergic signalling, Wnt signalling, GnRH signalling, ErbB signalling, and ECM-receptor interactions. Many genes involved in these pathways were also differentially expressed after E2 treatment. Specifically, E2 treatments resulted in upregulation of female-related genes and downregulation of male-related genes in genetic males during sex reversal. However, E2-induced sex reversal did not cause sex-specific changes in methylation profiles or gene expression within the sex determination region (SDR) on chromosome 4, suggesting that E2-induced sex reversal was a downstream process independent of the sex determination process that was regulated by sex-specific methylation within the SDR.

Preoperative Visualized Ultrasound Assessment of the Recurrent Laryngeal Nerve in Thyroid Cancer Surgery: Reliability and Risk Features by Imaging.

BACKGROUND: Preoperative identification and visualization of tumor infiltration of the recurrent laryngeal nerve (RLN) in patients with thyroid cancer is important. The purpose of our study was to evaluate the reliability and feasibility of preoperative assessment by ultrasound and to identify ultrasound imaging features potentially associated with tumor infiltration of the RLN. METHODS: In this prospective study, patients undergoing thyroid cancer surgery at our institution between August 2020 and January 2021 were included, and preoperative ultrasound visualization of the RLN and thyroid lesions was performed. RLN infiltration was also confirmed surgically in all cases. Five patients with enlarged lymph nodes were selected to undergo injection of carbon nanoparticles to confirm the correctness of RLN identification by preoperative ultrasound. The repeatability of RLN assessment by ultrasound was evaluated by comparing the correlation between pre- and intraoperative, intra- and inter-group assessments. Parameters of normal RLNs according to age, sex, and body mass index were established. Finally, ultrasound imaging features of patients with RLN tumor infiltration were analyzed to identify potential risk predictors. RESULTS: According to the ultrasonic assessment, RLNs of 70 patients appeared normal, while 14 of those patients appeared to be infiltrated by tumors. During surgery, the 70 cases of normal RLNs were confirmed, but only 8 of the 14 suspected cases of infiltration were confirmed. In all five patients injected with carbon nanoparticles, the location of RLNs adjacent to the marked lymph nodes observed by surgeons corresponded to the RLN location identified by preoperative ultrasound. The repeatability of RLN estimation varied from moderate to excellent. There were no significant differences in cross-sectional area, width, or thickness of normal RLNs according to age, sex, or body mass index. Indistinct margin with tumor, incontinuous shape as ultrasound features by the analysis of patients with surgically confirmed RLN infiltration were associated with tumor invasion. CONCLUSION: We show that preoperative ultrasound can be applied to visualize the RLN and may help predict tumor infiltration of the RLN.

KRT7 promotes epithelial­mesenchymal transition in ovarian cancer via the TGF­ß/Smad2/3 signaling pathway.

Keratin 7 (KRT7) is a member of the keratin gene family. KRT7 is abnormally expressed in various types of cancer and promotes the malignant progression of tumors. However, the role of KRT7 in ovarian cancer remains unclear. The present study aimed to validate the role of KRT7 in ovarian cancer progression. KRT7 expression levels in patients with ovarian cancer were analyzed using data obtained from the Human Protein Atlas and The Cancer Genome Atlas databases. KRT7 mRNA and protein expression levels were upregulated in ovarian cancer tissue compared with normal tissue. KRT7 expression was associated with the grading, staging and poor prognosis of ovarian cancer. The differentially expressed genes affected by KRT7 were primarily enriched in the functions of cell migration, cell adhesion and cell growth. In vitro studies, including a CCK8 assay, were used to detect cell proliferation. In addition, wound healing and transwell assays were performed to analyze cell migration. The results demonstrated that KRT7 overexpression was associated with increased proliferation, migration and epithelial­mesenchymal transition (EMT) of ovarian cancer cells, and the migration and EMT of ovarian cancers cells were decreased following knockdown with KRT7 small interfering RNA. In vivo, knockdown of KRT7 inhibited tumor growth of ovarian cancer. Furthermore, KRT7 regulated EMT in ovarian cancer via the TGF­ß/Smad2/3 pathway, and regulated cell­matrix adhesion through integrin­ß1­focal adhesion kinase signaling. These results suggest that KRT7 may be a potential molecular marker for prognosis prediction in patients with ovarian cancer.

Electron energy loss of ultraviolet plasmonic modes in aluminum nanodisks.

We theoretically investigated electron energy loss spectroscopy (EELS) of ultraviolet surface plasmon modes in aluminum nanodisks. Using full-wave Maxell electromagnetic simulations, we studied the impact of the diameter on the resonant modes of the nanodisks. We found that the mode behavior can be separately classified for two distinct cases: (1) flat nanodisks where the diameter is much larger than the thickness and (2) thick nanodisks where the diameter is comparable to the thickness. While the multipolar edge modes and breathing modes of flat nanostructures have previously been interpreted using intuitive, analytical models based on surface plasmon polariton (SPP) modes of a thin-film stack, it has been found that the true dispersion relation of the multipolar edge modes deviates significantly from the SPP dispersion relation. Here, we developed a modified intuitive model that uses effective wavelength theory to accurately model this dispersion relation with significantly less computational overhead compared to full-wave Maxwell electromagnetic simulations. However, for the case of thick nanodisks, this effective wavelength theory breaks down, and such intuitive models are no longer viable. We found that this is because some modes of the thick nanodisks carry a polar (i.e., out of the substrate plane or along the electron beam direction) dependence and cannot be simply categorized as radial breathing modes or angular (azimuthal) multipolar edge modes. This polar dependence leads to radiative losses, motivating the use of simultaneous EELS and cathodoluminescence measurements when experimentally investigating the complex mode behavior of thick nanostructures.

circKRT7-miR-29a-3p-COL1A1 Axis Promotes Ovarian Cancer Cell Progression.

BACKGROUND: Circular RNA (circRNA) has emerged as an important regulator in the progression of human diseases. However, the role of circRNAs in ovarian cancer remains largely unknown. MATERIALS AND METHODS: DNA sequencing and PCR were used to identify the existence and expression of circKRT7. The targeting relationship between circKRT7/miR-29a-3p and miR-29a-3p/COL1A1 was verified by fluorescence reporter assay. In vitro, colony formation, transwell and wound healing assay were used to detect the effects of circKRT7 and miR-29a-3p on the proliferation, migration and invasion ability of ovarian cancer cells. In vivo, xenograft tumor model was performed to validate the role of circKRT7 and miR-29a-3p in tumor growth. RESULTS: We found that circKRT7 can promote the proliferation and metastasis of ovarian cancer cells by absorbing miR-29a-3p, which leads to the up-regulation of COL1A1. In vitro, knock-down of circKRT7 can inhibit the migration and invasion of ovarian cancer cells. This effect of circKRT7 is achieved by adsorbing miR-29a-3p and subsequently COL1A1 release. In vivo experiments, the reduction of circKRT7 expression can also slow tumor growth, and this inhibition was partly counteracted after miR-29a-3p repression. CONCLUSION: Overall, circKRT7 promotes EMT-related cell progression by absorbing miR-29a-3p in ovarian cancer. This suggests the crucial role of circular RNA in the malignant evolution in cancer.

Genome-Wide DNA Methylation Signatures of Sea Cucumber Apostichopus japonicus during Environmental Induced Aestivation.

Organisms respond to severe environmental changes by entering into hypometabolic states, minimizing their metabolic rates, suspending development and reproduction, and surviving critical ecological changes. They come back to an active lifestyle once the environmental conditions are conducive. Marine invertebrates live in the aquatic environment and adapt to environmental changes in their whole life. Sea cucumbers and sponges are only two recently known types of marine organisms that aestivate in response to temperature change. Sea cucumber has become an excellent model organism for studies of environmentally-induced aestivation by marine invertebrates. DNA methylation, the most widely considered epigenetic marks, has been reported to contribute to phenotypic plasticity in response to environmental stress in aquatic organisms. Most of methylation-related enzymes, including DNA methyltransferases, Methyl-CpG binding domain proteins, and DNA demethylases, were up-regulated during aestivation. We conducted high-resolution whole-genome bisulfite sequencing of the intestine from sea cucumber at non-aestivation and deep-aestivation stages. Further DNA methylation profile analysis was also conducted across the distinct genomic features and entire transcriptional units. A different elevation in methylation level at internal exons was observed with clear demarcation of intron/exon boundaries during transcriptional unit scanning. The lowest methylation level occurs in the first exons, followed by the last exons and the internal exons. A significant increase in non-CpG methylation (CHG and CHH) was observed within the intron and mRNA regions in aestivation groups. A total of 1393 genes were annotated within hypermethylated DMRs (differentially methylated regions), and 749 genes were annotated within hypomethylated DMRs. Differentially methylated genes were enriched in the mRNA surveillance pathway, metabolic pathway, and RNA transport. Then, 24 hypermethylated genes and 15 hypomethylated genes were Retrovirus-related Pol polyprotein from transposon (RPPT) genes. This study provides further understanding of epigenetic control on environmental induced hypometabolism in aquatic organisms.

Preoperative fibrinogen-to-albumin ratio, a potential prognostic factor for patients with stage IB-IIA cervical cancer.

BACKGROUND: Previous studies have shown that fibrinogen-to-albumin ratio (FAR) is a novel prognostic immune biomarker in various diseases. In this study, we investigated the role of FAR in the prognosis of patients with stage IB-IIA cervical cancer (CC). METHODS: A total of 278 eligible participants with newly diagnosed CC (stage IB-IIA) who had undergone radical hysterectomy followed by adjuvant chemotherapy were enrolled in this study. Demographics, clinicopathological variables, and laboratory tests were obtained from the medical records. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were evaluated by univariate and multivariate Cox proportional regression analyses. The association between OS, RFS, and FAR was assessed by the Kaplan-Meier method using log-rank test. RESULTS: FAR was associated with age, International Federation of Gynecology and Obstetrics (FIGO) stage, depth of the invasion, and C-reactive protein (CRP) level (P < 0.05). Preoperative FAR was an effective predictor for OS in CC patients with a cut-off value of 7.75 and an area under the curve (AUC) of 0.707 (P < 0.001). The univariate and multivariate Cox analyses indicated that FIGO stage and FAR were two independent risk factors for both OS and RFS (P < 0.05). Kaplan-Meier analysis confirmed that patients with high FAR levels showed significantly lower RFS (P = 0.004) and OS (P = 0.003) than those with low FAR levels. CONCLUSIONS: This study indicated that elevated preoperative FAR might be a novel prognostic factor for CC patients with stage IB-IIA.