Pro-inflammatory cytokines and CXC chemokines as game-changer in age-associated prostate cancer and ovarian cancer: Insights from preclinical and clinical studies' outcomes.

Prostate cancer (PC) and Ovarian cancer (OC) are two of the most common types of cancer that affect the reproductive systems of older men and women. These cancers are associated with a poor quality of life among the aged population. Therefore, finding new and innovative ways to detect, treat, and prevent these cancers in older patients is essential. Finding biomarkers for these malignancies will increase the chance of early detection and effective treatment, subsequently improving the survival rate. Studies have shown that the prevalence and health of some illnesses are linked to an impaired immune system. However, the age-associated changes in the immune system during malignancies such as PC and OC are poorly understood. Recent research has suggested that the excessive production of inflammatory immune mediators, such as interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor (TGF), tumor necrosis factor (TNF), CXC motif chemokine ligand 1 (CXCL1), CXC motif chemokine ligand 12 (CXCL12), and CXC motif chemokine ligand 13 (CXCL13), etc., significantly impact the development of PC and OC in elderly patients. Our review focuses on the latest functional studies of pro-inflammatory cytokines (interleukins) and CXC chemokines, which serve as biomarkers in elderly patients with PC and OC. Thus, we aim to shed light on how these biomarkers affect the development of PC and OC in elderly patients. We also examine the current status and future perspective of cytokines (interleukins) and CXC chemokines-based therapeutic targets in OC and PC treatment for elderly patients.

An EMT-related genes signature as a prognostic biomarker for patients with endometrial cancer.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC. METHODS: RNA sequencing profiles of EC patients obtained from The Cancer Genome Atlas (TCGA) database were used to screen differential expression genes (DEGs) between tumors and normal tissues. The Cox regression model with the LASSO method was utilized to identify survival-related DEGs and to establish a prognostic signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC) and calibration curve. Eventually, functional enrichment analysis and cellular experiments were performed to reveal the roles of prognosis-related genes in EC progression. RESULTS: A total of 540 EMT-related DEGs in EC were screened, and subsequently a four-gene risk signature comprising SIRT2, SIX1, CDKN2A and PGR was established to predict overall survival of EC. This risk signature could serve as a meaningfully independent indicator for EC prognosis via multivariate Cox regression (HR = 2.002, 95%CI = 1.433-2.798; P < 0.001). The nomogram integrating the risk signature and clinical characteristics exhibited robust validity and performance at predicting EC overall survival indicated by ROC and calibration curve. Functional enrichment analysis revealed that the EMT-related genes risk signature was associated with extracellular matrix organization, mesenchymal development and cellular component morphogenesis, suggesting its possible relevance to epithelial-mesenchymal transition and cancer progression. Functionally, we demonstrated that the silencing of SIX1, SIRT2 and CDKN2A expression could accelerate the migratory and invasive capacities of tumor cells, whereas the downregulation of PGR dramatically inhibited cancer cells migration and invasion. CONCLUSIONS: Altogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients.

Exploring cytokines dynamics: Uncovering therapeutic concepts for metabolic disorders in postmenopausal women- diabetes, metabolic bone diseases, and non-alcohol fatty liver disease.

Menopause is an age-related change that persists for around one-third of a woman's life. Menopause increases the risk of metabolic illnesses such as diabetes, osteoporosis (OP), and nonalcoholic fatty liver disease (NAFLD). Immune mediators (pro-inflammatory cytokines), such as interleukin-1 (IL-1), IL-6, IL-17, transforming growth factor (TGF), and tumor necrosis factor (TNF), exacerbate the challenges of a woman undergoing menopause by causing inflammation and contributing to the development of these metabolic diseases in postmenopausal women. Furthermore, studies have shown that anti-inflammatory cytokines such as interleukin-1 receptor antagonists (IL-1Ra), IL-2, and IL-10 have a double-edged effect on diabetes and OP. Likewise, several interferon (IFN) members are double-edged swords in the OP. Therefore, addressing these immune mediators precisely may be an approach to improving the health of postmenopausal women. Hence, considering the significant changes in these cytokines, the present review focuses on the latest findings concerning the molecular mechanisms by which pro- and anti-inflammatory cytokines (interleukins) impact postmenopausal women with diabetes, OP, and NAFLD. Furthermore, we comprehensively discuss the therapeutic approaches that identify cytokines as therapeutic targets, such as hormonal therapy, physical activities, natural inhibitors (drugs), and others. Finally, this review aims to provide valuable insights into the role of cytokines in postmenopausal women's diabetes, OP, and NAFLD. Deeply investigating the mechanisms and therapeutic interventions involved will address the characteristics of immune mediators (cytokines) and improve the management of these illnesses, thereby enhancing the general quality of life and health of the corresponding populations of women.

ZFHX2-AS1 interacts with DKC1 to regulate ARHGAP5 pseudouridylation and suppress ovarian cancer progression.

Ovarian cancer (OCa) remains a highly lethal disease, largely due to late-stage diagnosis and limited treatment options for recurrent metastatic tumors. Long non-coding RNAs (lncRNAs) have been recognized as key regulators of cancer hallmarks, yet their specific roles in driving OCa progression are not fully understood. In this study, we employed an integrated approach combining clinical correlation, functional assays, and mechanistic investigations to reveal that lncRNA ZFHX2-AS1 is significantly downregulated in OCa tissues and cells, with its reduced expression associated with poor clinical outcomes. Using in vitro and in vivo models, we demonstrated that overexpression of ZFHX2-AS1 suppresses OCa cell proliferation, migration and invasion, whereas ZFHX2-AS1 knockdown enhances these malignant phenotypes. Mechanistically, we defined that ZFHX2-AS1 interacts with and attenuates the enzymatic activity of the pseudouridine synthase DKC1, thereby reducing pseudouridylation and stabilizing the oncogenic ARHGAP5 mRNA. Re-expression of ARHGAP5 could partially reverse the tumor-suppressive effects of ZFHX2-AS1. Further, we found that ARHGAP5 promotes epithelial-mesenchymal transition (EMT) by regulating Rho GTPases activities, and that ZFHX2-AS1 inhibits EMT in OCa by downregulating ARHGAP5 expression and suppressing the Rho GTPase signaling pathway. Taken together, our findings identify ZFHX2-AS1 as a potent tumor suppressor in OCa, acting through the modulation of DKC1-mediated pseudouridylation of ARHGAP5 and the inhibition of the Rho GTPase pathway, thus offering a potential therapeutic target for combating OCa progression.

China's sustainable carbon neutral supply chain management: a reference to global emission reduction.

Carbon emissions are a critical concern in the realm of energy consumption, with many nations committed to curbing them and striving for carbon neutrality. This research addresses a specific gap in the literature by focusing on carbon emission reduction in the industrial sector through the application of supply chain management (SCM) principles under a monopolistic competition context and by utilizing carbon neutral indicators. Specifically, we develop a mathematical model integrated into an agent-based simulation framework and employ experimental design methods to determine the most optimal decision-making processes for incorporating supply chain carbon neutral indicators. Our findings highlight the effectiveness of two specific carbon neutral indicators within SCM: green-credit policies and the promotion of green products. These measures contribute significantly toward reducing global carbon emissions. This paper offers insights for government decision-makers regarding ideal implementation levels and strategies for green credit policies and the promotion of green products within supply chain environments. It also provides guidance to manufacturers on how to achieve profit maximization while progressing towards carbon neutrality.

A novel LINC00478 serves as a tumor suppressor in endometrial carcinoma progression.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and progression of various cancers, but their roles in endometrial cancer (EC) are largely unknown. METHODS: The expressions of LINC00478 and PTBP1 in EC tissues were determined by RT-qPCR. Cell counting kit-8, flow cytometry and Transwell assays were executed for detecting the roles of LINC00478 in EC cells proliferation, migration and invasion. The mouse-xenograft models were established by subcutaneous injection in vivo. The interaction between LINC00478 and PTBP1 was confirmed by RNA pull-down assay and RNA-binding protein immunoprecipitation assay. RESULTS: LINC00478 was significantly down-regulated in EC tissues while compared to that in their paracancerous samples, and a higher expression level of LINC00478 was negatively correlated with clinical progress of EC patients. Functional experiments in vivo and in vitro revealed that LINC00478 overexpression could dramatically retard the proliferation of EC cells, decrease the rate of colony formation, suppress the migration and invasion abilities of EC cells in vitro and inhibit tumor growth in vivo. Mechanistically, LINC00478 regulated the expression of PTBP1, a key factor in the Warburg effect, and affected the metabolic process of EC cells. CONCLUSIONS: LINC00478 acts as a tumor suppressor in EC by negatively controlling PTBP1 expression and influencing the Warburg effect, providing a potential biomarker and therapeutic target for patients with EC.

Ribonuclease A Family Member 2 Promotes the Malignant Progression of Glioma Through the PI3K/Akt Signaling Pathway.

The treatment of patients with glioma still faces many difficulties. To further optimize treatment, it is necessary to identify more accurate markers as treatment targets and predict prognostic indicators. RNASE2 was identified as a differentially expressed gene (DEG) in glioma tissues using bioinformatics analysis. In glioma microarrays, 31.21% (54/173) and 68.79% (119/173) patients showed low and high RNASE2 protein expression levels, respectively. RNASE2 protein levels were considerably correlated with age, WHO grade, relapse, and death. Both mRNA and protein levels were associated with the overall survival of patients with glioma. To investigate the role of RNASE2, it was overexpressed or silenced in glioma cells. RNASE2 overexpression promoted cell proliferation, migration, and invasion. In addition, its overexpression promoted the growth of subcutaneous tumors and lung metastasis of glioma cells. Key protein levels in the PI3K/Akt signaling pathway were upregulated by RNASE2 overexpression. In contrast, RNASE2 knockdown had the opposite effects. Furthermore, LY294002 blocked the effects of RNASE2 on the cell function of glioma cells. In conclusion, RNASE2 is a novel marker associated with the diagnosis and prognosis of patients with glioma, and it promotes the malignant progression of gliomas through the PI3K/Akt signaling pathway.

[Expressions of micro-calpain mRNA and protein in cerebral tissues of neonatal rats after hypoxic-ischemic brain damage].

OBJECTIVE: To identify the expression of micro-calpain mRNA and protein in cerebral tissues of neonatal rats after hypoxic-ischemic brain damage (HIBD) and its role in the pathogenesis of HIBD. METHODS: Seven-day-old Sprague-Dawley rats were randomly divided into seven groups: control group and groups with 0, 6, 12, 24, 48, and 72 hours of exposure to HIDB. Quantitative real-time fluroscent polymerase chain reaction and Western blot technique were employed to detect the expression of micro-calpain mRNA and its protein respectively. RESULTS: The micro-calpain mRNA in the ipsilateral cerebral tissues began to increase 6 hours after the HIDB and reached peak at 24 hours, and then gradually decreased but remained in a higher level than that of the control group until at 72 hours (P < 0.05). The activated micro-calpain protein started to increase 6-12 hours after the HIDB (P < 0.05) and reached peak at 24 hours (P < 0.01). Higher levels of micro-calpain protein were maintained until 48 and 72 hours after the HIBD (P < 0.05). CONCLUSION: The expressions of micro-calpain mRNA and protein increase with the HIBD. The micro-calpain may play a role in the pathogenesis of the HIBD.

[Alternations of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kidney ischemic Injury].

OBJECTIVE: To study the changes of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kindney ischemic injury. To explore the interactions between ADF and G-actin and their relationships with actin cytoskeleton. METHODS: Twenty-four neonatal rats were used to the experiments due to have the weights from 30 to 40 g respectively. Renal ischemia was induced by clamping the left renal pedicle for different periods of time that was in 10 min or 30 min. The kidneys of normal neonatal rats were functioned as the control group. Two kinds of primary antibodies, which one was rabbit anti-chick ADF antiserum and another was mouse monoclonal G-actin antibody, were used on one same section of kidney tissue. FITC-labeled and TRITC-labeled secondary antibodies were used to identify ADF and G-actin respectively. These samples were examined by using a fluorescene microscope. RESULTS: In control group, ADF and G-actin showed to be diffused in cytoplasm of renal tubular epithelial cell. In ischemic injury group, the distributions of ADF and G-actin were changed significantly to apical region of tubular epithelial cells and the renal tubula lumen. Regardless of the ADF expression to not change but G-actin was increased after kidney ischemia. CONCLUSION: Under the physiolgical condition, ADF and G-actin got a diffuse distribution in cytoplasm of renal tubular epitbelial cell. However, when the kidney got in ischemia, the distributions of ADF and G-actin were changed significantly to apica region of tubular epithelial cell or the renal tubular lumen.

WWOX CNV-67048 Functions as a Risk Factor for Epithelial Ovarian Cancer in Chinese Women by Negatively Interacting with Oral Contraceptive Use.

Copy number variations (CNVs) have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC). Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX) was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV-67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (±5 years) matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy) conferred a significantly increased risk of EOC (OR = 1.346, 95% CI = 1.037-1.747) and it determined the risk by means of copy number-dependent dosage effect (P = 0.009). Data from TCGA also confirmed the abovementioned association as the frequency of low copies in EOC group was 3.68 times more than that in healthy group (P = 0.023). The CNV also negatively interacted with oral contraceptive use on EOC risk (P = 0.042). Functional analyses further showed a lower mRNA level of WWOX in tissues with the 0-copy or 1-copy than that in those with the 2-copy (P = 0.045). Our data suggested the CNV-67048 to be a risk factor of EOC in Chinese women.

[The function of integrin beta 1 in the hypoxic cellular damage mechanism of renal tubular epithelial cell of newborn porcine].

OBJECTIVE: To inquire into the mechanism of renal deficiency in neonatal asphyxia. METHODS: The 30, 60, 90, 120 min hypoxic renal cell model was made by use of DMEM/F-12 with antimycine A. ATP content was detected by reversed-phase HPLC. The levels of integrin beta 1 of renal tubular epithelial(RTE) cell of the groups were detected using flow cytometry. RESULTS: ATP deficiency cellular model of newborn porcine RTE cell was successfully set up. The levels of ATP of the newborn porcine RET cell during 30, 60, 90, 120 min hypoxia time significantly decreased as compared with normal control (P < 0.001). The levels of integrin beta 1 of newborn porcine RTE cell decreased as the ATP deficiency time increased and the differences between the groups were statistically significant (P < 0.001). CONCLUSION: The decreased level of integrin beta 1 in the newborn porcine RTE cell during anoxia may play an important role in the newborn renal deficiency during asphyxia.