IL-38 promotes the development of prostate cancer.

Introduction: Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment. Materials and methods: The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics. Results: There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients. Conclusion: These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

Exploring the clinical significance of IL-38 correlation with PD-1, CTLA-4, and FOXP3 in colorectal cancer draining lymph nodes.

Introduction: Colorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation. Results: Our investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients' nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations. Discussion: Our findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

CD64 plays a key role in diabetic wound healing.

Introduction: Wound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear. Objectives: We aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice. Methods: First, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry. Results: CD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators. Conclusion: CD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8.

Background: Colorectal cancer (CRC) is characterized by its aggressiveness and high fatality rate. Long noncoding RNAs (lncRNAs) as molecular scaffolding in CRC have received little attention. Methods: The TCGA database was used to find putative anti-oncogenic lncRNAs in CRC. The effect of FENDRR on CRC was evaluated using the colony formation assay, transwell assays, and wound healing assays, and FENDRR expression was validated by qRT-PCR. The location of the FENDRR binding proteins was determined by an RNA pull-down experiment, and the retrieved proteins were recognized by mass spectrometry. RNA immunoprecipitation (RIP) studies were used to demonstrate the interaction of GSTP1, FBX8, and FENDRR. Co-IP and immunofluorescence were utilized to confirm the connection between GSTP1 and FBX8. To determine the precise signaling pathways implicated in the action of FENDRR in CRC, we performed next-generation sequencing (NGS) on CRC cells transfected with a vector overexpressing FENDRR. Results: The expression of FENDRR was significantly downregulated in CRC tissue and cells. The results of the function experiments showed that overexpression of FENDRR reduced CRC cells' ability to proliferation, invasion, migration and tube formation. In terms of mechanism, FENDRR could bind both GSTP1 and FBX8, act as a molecular scaffold, and utilize FBX8 to regulate the stability of GSTP1's protein. Additionally, the outcomes of NGS and qRT-PCR demonstrated that the expression of genes linked to the HIF-1 pathway was down-regulated following FENDRR overexpression. Lastly, rescue tests demonstrated that overexpression of GSTP1 in CRC cells could completely restore the inhibition induced by FENDRR. Conclusion: In this study, we found that the molecular scaffolding protein FENDRR regulates the ubiquitination of GSTP1 and the suppression of the HIF-1 signaling pathway in the development of CRC. Our research provides more evidence of FENDRR's crucial role in the emergence of CRC and identifies it as a potential therapeutic target for CRC patients.

Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer.

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

Effects of acupuncture on Luteinized Unruptured Follicle Syndrome: A meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis aimed to evaluate the comprehensive efficiency and safety of acupuncture on Luteinized Unruptured Follicle Syndrome based on Randomized Controlled Trials (RCTs). METHODS: Six electronic databases (i.e. Wanfang, VIP, China National Knowledge Infrastructure, Pubmed, Cochrane, and Embase) were searched from inception to July 2019. Randomized controlled trials were eligible to evaluate the effects of acupuncture alone or acupuncture as an adjunct. The primary outcomes were the ovulation rate and pregnancy rate. Two reviewers proceeded study selection and quality assessment of included trials and performed heterogeneity of included studies before meta-analysis.Trial Sequential Analysis was used to assess the risk of random error and estimate required information size. The Grading of Recommendations Assessment, Development and Evaluation was applied for assessing level of evidence. RESULTS: 10 studies involving 715 participants were included Meta-analysis showed acupuncture alone and acupuncture as an adjunct both could significantly improve ovulation, which were confirmed by Trial Sequential Analysis. The evidence of acupuncture improving pregnancy rate was insufficient. Improved serum luteinizing hormone and estradiol levels, and decreased pulsatility index and resistance index of ovary artery were shown in both two subgroups. Level of evidence of most outcomes was "low" or "very low", so the results should be cautiously interpreted. CONCLUSIONS: Acupuncture alone or be combined with drugs are effective on Luteinized Unruptured Follicle Syndrome especially for improving ovulation . While concurrent evidence is insufficient, and further studies of high quality are needed to strengthen the conclusion.

IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß and IL-36γ in the prognosis of CRC is unclear. METHODS: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.

Interleukin-38 in colorectal cancer: a potential role in precision medicine.

Colorectal cancer (CRC) is a leading cause of cancer-related death, partly due to a lack of reliable biomarkers for early diagnosis. To improve the outcome of CRC, it is critical to provide diagnosis at an early stage using promising sensitive/specific marker(s). Using immunohistochemistry and histopathology, IL-38 expression was determined in tissue arrays of CRC with different TNM status and depth of tumour invasion. Data were compared to IL-38 in adjacent non-cancer tissue and correlated with demographic information, including survival. A substantial reduction of IL-38 was detected in the CRC tissue compared to adjacent non-cancer colonic tissue. IL-38 correlated with the extent of tumour differentiation (P < 0.0001); CRC location in the left side of the colon (P < 0.05), and smaller tumour size (≤ 5 cm; P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated both high specificity and high sensitivity of IL-38 for the diagnosis of CRC [area under the curve (AUC) = 0.89)]. By sub-group analysis, AUC of IL-38 for the diagnosis of CRC was higher in poorly differentiated, right-sided CRC or tumour size > 5 cm (all AUC > 0.9). Significantly, longer survival was observed for the IL-38high versus the IL-38low groups in CRC patients (P = 0.04). Survival was also longer for IL-38high patients with lymph node metastasis (P = 0.01) and TNM stage III-IV (P = 0.02). Multivariate analysis demonstrated that IL-38 (P = 0.05) and tumour invasion depth (P = 0.04) were independent factors for survival. High IL38 in CRC is an independent prognostic factor for the longer survival of CRC patients. IL-38 signalling may constitute a therapeutic target in CRC.

Clinical significance of urothelial carcinoma associated 1 in colon cancer.

This study aimed to investigate the expression levels of urothelial carcinoma associated 1 (UCA1) in cancer tissues and plasma of colon cancer patients, and evaluate its clinical significance. Quantitative real-time PCR was used to determine the expression levels of UCA1 in 80 pairs of colon cancer and adjacent normal tissues, plasma samples from 20 healthy controls, 20 colon cancer patients before and after tumor removal. The relationships between UCA1 expression and clinical features and overall survival were analyzed. Compared with adjacent normal tissues, UCA1 was significantly upregulated in colon cancer tissues, especially in cases with LNM and advanced TNM stages (P < 0.05). High UCA1 expression was associated with LMN, higher pT category, and advanced TNM stages (P < 0.05). Patients with high UCA1 expression had worse survival time than those with low UCA1 expression (adjusted HR = 2.002, 95% CI 1.007-3.981, P = 0.048). Furthermore, plasma levels of UCA1 in colon cancer patients were significantly higher than those of controls (P = 0.016). There was significant difference in plasma level of UCA1 between samples taken before and after surgery (P = 0.048). In conclusion, tissue expression of UCA1 is related to prognosis in colon cancer. Plasma UCA1 may serve as a potential biomarker for early diagnosis and disease monitoring of colon cancer patients.

Comparative study of the cervista and hybrid capture 2 methods in detecting high-risk human papillomavirus in cervical lesions.

High-risk human papillomavirus (HR HPV) testing is important for the follow-up of patients with cytological abnormalities. This study was undertaken to compare the clinical value of the Cervista and hybrid capture 2 (HC2) tests for detection of HR HPV in cervical lesions. Overall 439 cervical specimens with abnormal cytology and 22 normal cervical specimens were subjected to the Cervista and HC2 tests. HPV positivity and its predictive value for high-grade cervical lesions were assessed. The Cervista and HC2 tests showed comparable HR HPV detection rates in women with all cytological and histological diagnoses, with a positive and negative percent agreement of 90.8% and 64.5%, respectively. The two methods had a same sensitivity of 90% in detecting CIN II or greater cervical lesions, while the specificity for the Cervista test and HC2 assay was 47% and 43%, respectively. The positive rate for the Cervista assay probe set A9 increased with the histological severity, ranging from 25.0% in normal specimens to 69.5% in high-grade lesions. In conclusion, the clinical performance for the Cervista test is as excellent as the HC2 test in detecting HR HPV and predicting high-grade cervical lesions.

[Value of computer-assisted slide-screening system in ThinPrep cervical cytology].

OBJECTIVE: To investigate the value of computer-assisted slide-screening system (ThinPrep imaging system, TIS) in the diagnosis of cervical Thinprep smears. METHODS: A total of 19 600 ThinPrep smears were collected, including 9800 slides by TIS-assisted screening from September 2011 to March 2012 and 9800 slides by manual screening from September 2010 to April 2011 as control. The detection rates of abnormal cells and common microbial infection by the different screening methods were compared. With histopathological diagnosis of colposcopic biopsy as the gold standard, the screening efficiency and correlation of cytologic diagnosis among different screening methods were analyzed. RESULTS: Compared with manual screening, the detection rate of abnormal cells in 9800 cases by TIS-assisted screen was increased from 5.4% (525/9800) to 6.8% (665/9800), mainly in the categories of ASCUS and LSIL (P < 0.05). TIS had a higher accordance rate between cytologic diagnosis and histopathological diagnosis in the NILM and ASCUS than that by manual screening. False-negative rate of finding abnormal cells by TIS decreased from 8.5% (17/200) to 0.7% (2/289, P < 0.01) with an increased sensitivity compared to manual screening, although the specificity was similar. Both TIS and manual screening had advantages and disadvantages respectively in the detection of microbial organisms. TIS improved screening efficiency by 50%. CONCLUSION: TIS improves not only the screening efficiency but also the detection of abnormal cells with a reduced false negativity, and it therefore has a broad application prospect.

Calculations of stopping powers and inelastic mean free paths for 20 eV-20 keV electrons in 11 types of human tissue.

Systematic calculations are performed for determining the stopping powers (SP) and inelastic mean free paths (IMFP) for 20 eV-20 keV electrons in 11 types of human tissue. The calculations are based on a dielectric model, including the Born-Ochkur exchange correction. The optical energy loss functions (OELF) are empirically evaluated, because of the lack of available experimental optical data for the 11 tissues under consideration. The evaluated OELFs are examined by the f-sum rule expected from the dielectric response theory, and by calculation of the mean excitation energy. The calculated SPs are compared with those for PMMA (polymethylmethacrylate, a tissue equivalent material) and liquid water. The SP and IMFP data presented here are the results for the 11 human tissues over the energy range of 20 eV-20 keV, and are of importance in radiotherapy planning and for studies of various radiation effects on human tissues.