DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration.

BACKGROUND: Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood. METHODS: Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression. RESULTS: Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration. CONCLUSIONS: Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

The role of ST3GAL4 in glioma malignancy, macrophage infiltration, and prognostic outcomes.

Background: Glioma, a prevalent malignancy of the brain and spinal cord, poses a considerable threat to human health. The association between aberrant sialic acid modification and glioma progression has been suggested, but the precise mechanism is still elusive. ST3GAL4, a sialoglycosyltransferase, is implicated in increased metastatic potential and poor prognosis in various cancers; however, its specific role in glioma requires further elucidation. Methods: We evaluated ST3GAL4 expression levels and their clinical relevance using the TCGA database, and we assessed immune infiltration via the Tumor Immune Evaluation Resource (TIMER) database. In vitro experiments were performed to determine the effects of ST3GAL4 knockdown on glioma cell malignancy, with additional co-culture assays to assess its impact on macrophage phenotype. Results: ST3GAL4 expression was markedly elevated in glioma tissues compared to normal brain tissues, with a strong correlation to glioma patient clinical characteristics. Survival analyses and receiver operating characteristic (ROC) curves suggested that ST3GAL4 is a feasible diagnostic and prognostic biomarker for glioma. Knockdown studies revealed that ST3GAL4 inhibition reduces glioma cell line proliferation, migration, and invasion, while causing G1 phase cell cycle arrest. ST3GAL4 appears to mediate glioma progression through extracellular matrix reorganization and EMT signaling pathway activation, further contributing to M2 macrophage polarization and infiltration within the tumor microenvironment. Conclusion: Our research highlights the critical role of ST3GAL4 in glioma development, positioning it as a promising candidate for diagnostic and therapeutic interventions.

PLEKHA4 promotes glioblastoma progression through apoptosis inhibition, tumor cell migration, and macrophage infiltration.

BACKGROUND: Glioblastoma(GBM) has a profound impact on human health, making the identification of reliable prognostic biomarkers pivotal. While PLEKHA4 has been associated with tumor genesis and development, its role in gliomas is still uncertain. METHODS: We analyzed PLEKHA4 expression in tumor tissues using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we utilized TCGA data to investigate its impact on prognosis, pathway enrichment, and immune infiltration. In vitro loss-of-function experiments were conducted to elucidate the effect of PLEKHA4 silencing on GBM cell behavior. RESULTS: TCGA and GEO data sets revealed increased levels of PLEKHA4 expression in glioma tissues. Furthermore, we identified a correlation between PLEKHA4 expression and higher disease classification, pathological grading, and poorer prognosis. Silencing PLEKHA4 in vitro resulted in decreased glioma cell migration and increased apoptosis. It also reduced macrophage infiltration and hindered M2 polarization of macrophages. CONCLUSION: Our findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.

In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection.

The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1ß. Protein-protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.

Treatment of patients with metastatic epidural spinal cord compression using an enhanced recovery after surgery program.

Purpose: The aims of this study were to introduce a new medical, pathway based on the concept of "enhanced recovery after surgery" (ERAS) for patients with metastatic epidural spinal cord compression (MESCC), and to test whether the ERAS program could improve clinical metrics among such patients. Methods: Data from patients with MESCC (n = 98), collected between December 2016 and December 2019 (Non-ERAS cohort), and from 86 patients with metastatic epidural spinal cord compression collected between January 2020 and December 2022 (ERAS cohort), were retrospectively analyzed. Patients were treated by decompressive surgery combined with transpedicular screw implantation and internal fixation. Patient baseline clinical characteristics were collected and compared between the two cohorts. Surgical outcomes analyzed included operation time; intraoperative blood loss; postoperative length of hospital stay; time to ambulation, regular diet, urinary catheter removal, and radiation therapy; perioperative complications; anxiety; depression; and satisfaction with treatment. Results: No significant differences in clinical characteristics were found between the non-ERAS and enhanced recovery after surgery cohorts (all p > 0.050), indicating that the two cohorts were comparable. Regarding surgical outcomes, the enhanced recovery after surgery cohort had significantly less intraoperative blood loss (p < 0.001); shorter length of postoperative hospital stay (p < 0.001); shorter time to ambulation (p < 0.001), regular diet (p < 0.001), urinary catheter removal (p < 0.001), radiation administration (p < 0.001), and systemic internal therapy (p < 0.001); lower perioperative complication rate (p = 0.024); less postoperative anxiety (p = 0.041); and higher score for satisfaction with treatment (p < 0.001); whereas operation time (p = 0.524) and postoperative depression (p = 0.415) were similar between the two cohorts. Compliance analysis demonstrated that ERAS interventions were successfully conducted in the vast majority of patients. Conclusion: The enhanced recovery after surgery intervention is beneficial to patients with metastatic epidural spinal cord compression, according to data on intraoperative blood loss; length of hospital stay; time to ambulation, regular diet, urinary catheter removal, radiation exposure, and systemic internal therapy; perioperative complication; alleviation of anxiety; and improvement of satisfaction. However, clinical trials to investigate the effect of enhanced recovery after surgery are needed in the future.

Association of Tumor Cell Metabolic Subtype and Immune Response With the Clinical Course of Hepatocellular Carcinoma.

AIM: Tumor metabolism plays an important role in tumorigenesis and tumor progression. This study evaluated the potential association of tumor cell metabolism and immune cell tumor infiltration with the clinical course of hepatocellular carcinoma (HCC). METHODS: Gene-wise normalization and principal component analysis were performed to evaluate the metabolic system. A tumor microenvironment score system of tumor immune cell infiltration was constructed to evaluate its association with metabolic subtypes. Finally, we analyzed the impact of metabolism and immune cell infiltration on the clinical course of HCC. RESULTS: A total of 673 HCC patients were categorized into cholesterogenic (25.3%), glycolytic (14.6%), mixed (10.4%), and quiescent (49.8%) types based on glycolysis and cholesterol biosynthesis gene expression. The subgroups including the glycolytic genotyping expression (glycolytic and mixed types) showed a higher mortality rate. The glycolytic, cholesterogenic, and mixed types were positively correlated with M0 macrophage, resting mast cell, and naïve B-cell infiltration (P = .013, P = .019, and P = .006, respectively). In TCGA database, high CD8+ T cell and low M0 macrophage infiltration were associated with prolonged overall survival (OS, P = .0017 and P < .0001, respectively). Furthermore, in glycolytic and mixed types, patients with high M0 macrophage infiltration had a shorter OS (P = .03 and P = .013, respectively), and in quiescent type, patients with low naïve B-cell infiltration had a longer OS (P = .007). CONCLUSIONS: Tumor metabolism plays a prognostic role and correlates with immune cell infiltration in HCC. M0 macrophage and CD8+ T cell appear to be promising prognostic biomarker for HCC. Finally, M0 macrophages may represent a useful immunotherapeutic target in patients with HCC.

Association of mental health status between self-poisoning suicide patients and their family members: a matched-pair analysis.

BACKGROUND: The objective of this study was to examine the relationship of mental health status between self-poisoning suicide patients and their family members, and it also sought to identify potential patient's risk and parental factors for the prediction of suicide attempt, anxiety, and depression. METHODS: In this study, 151 poisoned patients were prospectively included, and they were matched 1:1 with 151 family members. We gathered information on patient's and their matched family member's demographics, lifestyle choices, mental health status, level of intimacy, and history of psychiatry disease. The relationship of patient's and their family member's mental health state was investigated using a correlation matrix. Multivariable analyses (multiple logistic regression) were conducted among patients and their matched family members, to identify potential risk factors for self-poisoning suicide, anxiety, and depression. RESULTS: Of the total patients, 67.55% (102/151) attempted self-poisoning suicide. Poisoned patients had more severe anxiety and depression symptoms than their matched family members, and this difference was even more pronounced among patients with self-poisoning suicide. Generalized anxiety disorder-7 (GAD-7) score for family members was significantly and favorably correlated with patient's GAD-7 score after eliminating non-suicide patients and their matched family members. The patient health questionnaire-9 (PHQ-9) score showed a similar pattern, and the family member's PHQ-9 score was strongly and favorably associated with patient's PHQ-9 and Beck hopelessness scale-20 (BHS-20) score. Multivariable analysis showed that married marital status (P = 0.038), quitting smoking (P = 0.003), sedentary time of 1 to 6 h (P = 0.013), and participation in a sports more than five times per week (P = 0.046) were all significantly associated with a lower risk of suicide by self-poisoning, while a more serious anxiety state (P = 0.001) was significantly associated with a higher risk of self-poisoning suicide. Multivariable analysis demonstrated that, specifically among self-poisoning suicide patients, married marital status (P = 0.011) and no history of psychiatry disease (P < 0.001) were protective factors for anxiety, while divorced or widowed marital status (P = 0.004), a sedentary time of 1 to 3 h (P = 0.022), and a higher monthly income (P = 0.027) were significant contributors to anxiety. The propensity of additional family-matched characteristics to predict patient's suicidality, anxiety, and depression was also examined. CONCLUSIONS: Self-poisoning suicide patients have severe mental health issues. Patients who self-poison have a close connection to their family member's mental health, particularly their levels of anxiety and depression. According to the findings, being married and adopting healthy lifestyle habits, such as quitting smoking and drinking, increasing their physical activity levels, and managing their idle time, are able to help patients with mental health concerns and even suicidal thoughts.

M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors.

BACKGROUND: Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. METHODS: In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. RESULTS: After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. CONCLUSIONS: We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.

Identification of risk factors for attempted suicide by self-poisoning and a nomogram to predict self-poisoning suicide.

Purpose: Suicide is a global concern, especially among young people. Suicide prediction models have the potential to make it easier to identify patients who are at a high risk of suicide, but they have very little predictive power when there is a positive value for suicide mortality. Therefore, the aim of the study is to uncover potential risk factors associated with suicide by self-poisoning and further to provide a trustworthy nomogram to predict self-poisoning suicide among poisoned patients. Methods: This study prospectively enrolled 237 patients who were treated for poisoning at the Fifth Medical Center of PLA General Hospital (Beijing) between May 2021 and May 2022. Patient's basic characteristics, daily activities, mental health status, and history of psychological illnesses were gathered to examine their predictive power for self-poisoning suicide. On developing a prediction model, patients were split 8:2 into a training (n = 196) group and a validation (n = 41) group at random via computer. The training group worked on model development, while the validation group worked on model validation. In this study, the Hosmer and Lemeshow test, accuracy, and area under the curve were the primary evaluation criteria. Shapley Additive exPlanations (SHAP) was determined to evaluate feature importance. To make the prediction model easy for researchers to utilize, it was presented in nomogram format. Two risk groups of patients were identified based on the ideal cut-off value. Results: Of all poisoned patients, 64.6% committed suicide by self-poisoning. With regard to self-poisoning attempted suicide, multivariate analysis demonstrated that female gender, smoking, generalized anxiety disorder-7 (GAD-7), and beck hopelessness scale-20 (BHS-20) were significant risk factors, whereas married status, relatively higher education level, a sedentary time of 1-3 h per day, higher sport frequency per week, higher monthly income were significant protective features. The nomogram contained each of the aforementioned nine features. In the training group, the area under curve (AUC) of the nomogram was up to 0.938 (0.904-0.972), whereas in the validation group, it reached a maximum of 0.974 (0.937-1.000). Corresponding accuracy rates were up to 0.883 and 0.927, respectively, and the P-values for the Hosmer and Lemeshow test were 0.178 and 0.346, respectively. SHAP demonstrated that the top three most important features were BHS-20, GAD-7, and marital status. Based on the best cut-off value of the nomogram (40%), patients in the high-risk group had a nearly six-time larger likelihood of committing suicide by self-poisoning than patients in the low-risk group (88.68 vs. 15.38%, P < 0.001). The dynamic nomogram was made available at the following address: https://xiaobo.shinyapps.io/Nomogramselfpoisoningsuicide/. Conclusions: This study proposes a prediction model to stratify patients at a high risk of suicide by self-poisoning and to guide individual preventive strategies. Patients in the high-risk group require further mental health counseling to alleviate anxiety and hopelessness, healthy lifestyle like quitting smoking and exercising more, and restriction of access to poison and psychiatric drugs.

Efficient optimization and development of two methods for the determination of acrylamide in deep-frying oil by liquid chromatography-tandem mass spectrometry: Application of multifactor analysis assessment strategy.

A new multifactor analysis assessment strategy was developed for evaluating, optimizing, and comparing analytical techniques for acrylamide in frying oils. Based on five indices (absolute recovery, absolute matrix effect, the intensity of the full ion scan, and the precursor ion scan to m/z 184 and m/z 241), the proposed strategy was performed with radar analysis, relative contribution analysis, and the entropy-weighted technique for order performance by similarity to ideal solution analysis. Two novel methods based on quick, easy, cheap, effective, rugged, and safe extraction methodology and gel permeation chromatography-liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry have been developed for the analysis of acrylamide in frying oils. Two methods were suitable for rapid and sensitive analysis of acrylamide in oils in different laboratories, with a limit of quantitation at 2 µg/kg, and the average recovery ranging from 92.5% to 107.8%, with relative standard deviations below 10%. When considering automation efficiency and matrix effects, gel permeation chromatography is the most efficient method, whereas the other method has an advantage when analyzing large samples. The developed methods were used in a pilot study to analyze frying oils with acrylamide content below 9.82 µg/kg, showing that the repeated frying process did not produce significant content of acrylamide in oils.

Uncovering the Heterogeneity and Clinical Relevance of Circulating Tumor-Initiating Cells in Hepatocellular Carcinoma Using an Integrated Immunomagnetic-Microfluidic Platform.

Circulating tumor-initiating cells (CTICs) with stem cell-like properties play pivotal roles in tumor metastasis and recurrence. However, little is known about the biology and clinical relevance of CTICs in hepatocellular carcinoma (HCC). Here, we investigated the molecular heterogeneity and clinical relevance of CTICs in HCC using a novel integrated immunomagnetic-microfluidic platform (iMAC). We constructed the iMAC and evaluated its ability to detect CTICs using a series of spiked cell experiments. A four-channel microfluidic chip was applied to investigate the composition of CTICs in patients with primary and recurrent HCC utilizing microbeads labeled with one of four stem-related markers: epithelial cell adhesion molecule (EpCAM), CD133, CD90, and CD24. The dynamic changes of these four CTIC subsets were serially monitored during treatment courses. Finally, single-cell RNA profiling was used to reveal the molecular characteristics of the four CTIC subsets. The iMAC platform detected significantly more EpCAM+ CTICs in the blood samples from 33 HCC patients than the FDA-approved CellSearch system (0.92 ± 0.94 vs 0.23 ± 0.36, P < 0.001). The number of EpCAM+ CTICs (≥0.75/mL) detected by iMAC was a predictor of early recurrence (P = 0.007). The distinct stem-related markers' expression of CTICs could distinguish primary HCC, recurrent HCC, and TACE-resistant HCC. Single-cell transcriptional profiling proved the heterogeneity among individual CTICs and separated the four CTIC subsets into distinct phenotypes. Dissecting the heterogeneity of CTICs using the iMAC represents a novel and informative method for accurate CTIC detection and characterization. This innovative technology will enable more indepth cancer biology research and clinical cancer management than is currently available.

Surgical treatment and muscle protein analysis of V-pattern exotropia in craniosynostosis.

The purpose of this study was to compare the differences of V-pattern exotropia in craniosynostosis and normal children. 39 children were included in this study, 19 craniosynostosis and 20 children in control group. They underwent comprehensive ocular examinations and received strabismus surgery. The extraocular muscle samples were analysed. Compared with the control group, craniosynostosis group had larger deviation in primary and up gaze, larger V pattern, and more severe inferior oblique overaction. For 20-40, and 50-60 prism diopter exotropia, the lateral recession in the craniosynostosis group was larger than that in the control group, 7.13 ± 0.44 mm vs 6.71 ± 0.47 mm, 8.90 ± 0.21 mm vs 7.75 ± 0.46 mm (p = 0.025, 0.000). The anterior transposition of craniosynostosis group was more anterior than that of control group, posterior 1.03 ± 1.24 vs 2.68 ± 0.94 mm (p = 0.000). Compared with the control group, the extraocular muscle abnormality in craniosynostosis was significant, 32% vs 5% (p = 0.031). There were 40 proteins in craniosynostosis group, which were different from those in control group. A larger V pattern and larger deviation is common in craniosynostosis children. For the same PD of deviation, it usually needs more recession in craniosynostosis because of the thinner and weaker extraocular muscles. Collagen related proteins were increased in craniosynostosis, and decreased contraction related protein tropomodulin might play key role for the weakness of EOMs.

Tilapia Skin Peptides Ameliorate Cyclophosphamide-Induced Anxiety- and Depression-Like Behavior via Improving Oxidative Stress, Neuroinflammation, Neuron Apoptosis, and Neurogenesis in Mice.

Anxiety- and depression-like behavior following chemotherapy treatment occurs in cancer patients with high probability and no specific therapeutics are available for treatment and prevention of this complication. Here, tilapia skin peptides (TSP), a novel enzymatically hydrolyzed bioactive peptide mixture, obtained from tilapia (Oreochromis mossambicus) scraps, were studied on cyclophosphamide (CP)-induced anxiety- and depression-like behavior in mice. Mice were received intraperitoneal injection of CP for 2 weeks, while TSP was administered for 4 weeks. After the end of the animal experiment, behavioral, biochemical, and molecular tests were carried out. The mice decreased preference for sugar water, increased immobility time in the forced swimming and tail suspension test, and decreased travel distance in the open field test in the Model group, compared with the Control group. Abnormal changes in behavioral tests were significantly improved after the TSP treatment. Additionally, abnormalities on superoxide dismutase, malondialdehyde, glutathione peroxidase were rescued by administration of 1000 mg/kg/d TSP in mice than that of the Model group. TSP has normalized the expression of Iba-1 and the levels of TNF-α and IL-1ß in the hippocampus of mice, which indicated that TSP could observably ameliorate neuroinflammatory response in the hippocampus of mice. TSP ameliorated the apoptosis of hippocampal neurons of CA1 and CA3 regions in the TSP group vs. the Model group. The number of doublecortin positive cells was drastically increased by administering 1000 mg/kg/d TSP in mice vs. the Model group. Furthermore, TSP reversed the Nrf2/HO-1 signaling pathway, BDNF/TrkB/CREB signaling pathway, and reduced the Bcl-2/Bax/caspase-3 apoptosis pathway. In conclusion, TSP could restore CP-induced anxiety- and depression-like behavior via improving oxidative stress, neuroinflammation, neuron apoptosis, and neurogenesis in mice hippocampus.

CD155/SRC complex promotes hepatocellular carcinoma progression via inhibiting the p38 MAPK signalling pathway and correlates with poor prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. As a cell adhesion molecule, poliovirus receptor (PVR/CD155) is abnormally overexpressed in tumour cells, and related to tumour proliferation and invasion. However, the potential role and mechanism of CD155 have not yet been elucidated in HCC. METHODS: Immunohistochemistry, RT-PCR and Western blot assays were used to determine CD155 expression in HCC cell lines and tissues. Cell Counting Kit-8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration and invasion. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cox regression and Kaplan-Meier analyses were performed to explore the clinical significance of CD155. The role of CD155 in vivo was evaluated by establishing liver orthotropic xenograft mice model. RNA sequencing, bioinformatics analysis and co-immunoprecipitation assay were used to explore the downstream signalling pathway of CD155. RESULTS: CD155 was upregulated in HCC tissues and represented a promising prognostic indicator for HCC patients (n = 189) undergoing curative resection. High CD155 expression enhanced cell proliferation, migration and invasion, and contributed to cell survival in HCC. CD155 overexpression also induced epithelial-mesenchymal transition in HCC cells. CD155 function in HCC involved SRC/p38 MAPK signalling pathway. CD155 interacted with SRC homology-2 domain of SRC and promoted SRC activation, further inhibiting the downstream p38 MAPK signalling pathway in HCC. CONCLUSIONS: CD155 promotes HCC progression via the SRC/p38 MAPK signalling pathway. CD155 may represent a predictor for poor postsurgery prognosis in HCC patients.

Tilapia skin peptides restore cyclophosphamide-induced premature ovarian failure via inhibiting oxidative stress and apoptosis in mice.

Tilapia (Oreochromis mossambicus) skin high value-added compounds have not been fully utilized in tilapia processing. Here, the protective effects of tilapia skin peptides (TSP) on primary ovarian failure (POF) and their underlying mechanisms in mice were investigated. Cyclophosphamide (CP) was injected intraperitoneally (ip) for 14 days (10 mg kg-1 d-1) to establish a mouse model of POF. At the same time, the mice were given intragastrically (ig) TSP for 30 days (250 mg kg-1 d-1, 500 mg kg-1 d-1, and 1000 mg kg-1 d-1, respectively). The ovarian index, estrous cycle, hormone level, changes in the number of follicles at various levels, and biochemical tests were carried out at the end of the experiment. The body weight and ovarian index of mice in the POF group were markedly lower than that of the control group. Treatment with TSP reversed these changes significantly. TSP administration significantly restored the estrous cycle disorder of the mice versus that of the POF group. The level changes of progesterone (P), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) induced by CP were significantly reversed by TSP treatment. TSP inhibited oxidative stress in CP-induced mice by enhancing the total superoxide dismutase (T-SOD) activity and reducing malondialdehyde (MDA) levels in the ovaries. TSP improved the apoptosis of ovarian granulosa cells in CP-induced mice compared with the POF group. Furthermore, TSP regulated the Bcl-2/Bax/caspase-3 apoptosis pathway and enhanced the Nrf2/HO-1 signaling pathway. In conclusion, TSP could improve CP-induced POF via alleviating ovarian oxidative stress and granulosa cell apoptosis.

Hydroxytyrosol alleviates oxidative stress and neuroinflammation and enhances hippocampal neurotrophic signaling to improve stress-induced depressive behaviors in mice.

Hydroxytyrosol (HT), the main phenolic compound in olives and olive products, has antioxidative, anti-inflammatory, neuroprotective, and other physiological functions. The effects of HT on depression are unclear. The aim of this study was to explore the effects of HT on chronic unpredictable mild stress (CUMS) induced depressive-like behaviors. Mice were exposed to CUMS for 9 weeks and then treated with HT beginning in the second week and continuing for 7 weeks. Behavioral, biochemical, and molecular tests were conducted at the end of the experiment. The sucrose preference was significantly decreased in the CUMS group versus the healthy control group. Also, immobility times in forced swimming and tail suspension tests were increased in CUMS-induced mice, but treatment with HT significantly reversed this change. HT ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase activity and reducing reactive oxygen species and malondialdehyde levels in the hippocampus. HT administration significantly suppressed microglia activation and inhibited the expression of tumor necrosis factor alpha and interleukin 1 beta in the hippocampus versus the untreated group. The expression level of glial fibrillary acidic protein (GFAP) and the number of GFAP-immunoreactive astrocytes in the hippocampus were significantly augmented by HT. Furthermore, HT treatment increased the expression of hippocampal brain-derived neurotrophic factor (BDNF), phosphorylated tropomyosin receptor kinase B (p-TrkB), and phosphorylated c-AMP response element binding protein (p-CREB) compared with the untreated CUMS group. Overall, HT improved CUMS-induced depressive-like behaviors in mice by alleviating oxidative stress and neuroinflammation and by enhancing the BDNF/TrkB/CREB signaling pathway.

Air particulate matter pollution and circulating surfactant protein: A systemic review and meta-analysis.

OBJECTIVE: Air particulate matter (PM) pollution is associated with the alterations in circulating pulmonary damage proteins. But there are not consistent results among the epidemiological studies. The aim of this study is to investigate the alteration of surfactant protein (SP) from PM exposure. METHODS: We conducted a comprehensive meta-analysis by searching the databases of PubMed, Medline, EMBASE, Web of Science and CNKI before October 2020 which reported PM pollutants and surfactant protein in the population. The sources of heterogeneity were assessed by subgroup (smoking, particulate matter with different aerodynamic diameter, exposure duration) analysis. We also used the publication bias tests for the comprehensive assessment. RESULTS: This meta-analysis consisted of 10 studies with 1985 subjects. The results showed that the combined standardized mean difference (SMD) value was 0.05, 95% confidence interval (CI) was -0.07 to 0.17 for serum SP-A and -0.81 (95% CI: -1.41 to -0.21) for circulating SP-D. Among smokers, the combined SMD value of SP-A were 0.29 (95% CI: 0.05 to 0.52). We did not find the correlation between publication year of SP-A and SP-D and study heterogeneity. CONCLUSIONS: Circulating SP-D was significantly decreased by air particulate matter. Serum SP-A was significantly increased by PM exposure among smokers. Circulating surfactant protein may be considered as a biomarker for respiratory injury caused by air particulate matter.

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes.

OBJECTIVES: Increasing evidence suggest that long non-coding RNAs (lncRNAs) play critical roles in cancers. However, the expression pattern and underlying mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain incompletely understood. This study aimed to elucidate the functions and molecular mechanisms of a certain lncRNA in NSCLC. METHODS: LncRNA microarray was performed to identify differential expressed lncRNAs between pre- and postoperation plasma in NSCLC patients. The expression level of candidate lncRNA in NSCLC tissues, plasma and cells was determined by quantitative real-time PCR (qRT-PCR) and in situ hybridization. The functional roles of lncRNA were assessed in vitro and in vivo. Furthermore, RNA pull-down, RNA immunoprecipitation, microarray, qRT-PCR and rescue assays were conducted to explore the mechanism action of lncRNA in NSCLC cells. RESULTS: We identified a novel lncRNA (BRCAT54), which was significantly upregulated in preoperative plasma, NSCLC tissues and NSCLC cells, and its higher expression was associated with better prognosis in patients with NSCLC. Overexpression of BRCAT54 inhibited proliferation, migration and activated apoptosis in NSCLC cells. Conversely, knockdown of BRCAT54 reversed the suppressive effects of BRCAT54. Moreover, overexpression of BRCAT54 repressed NSCLC cell growth in vivo. Mechanistically, BRCAT54 directly bound to RPS9. Knockdown of RPS9 substantially reversed the promoting effects of si-BRCAT54 on cell proliferation and enhanced the inhibitive effect of si-BRCAT54 on BRCAT54 expression. In addition, silencing of RPS9 activated JAK-STAT pathway and suppressed calcium signaling pathway gene expressions. CONCLUSION: This study identified BRCAT54 as a tumor suppressor in NSCLC. Targeting the BRCAT54 and RPS9 feedback loop might be a novel therapeutic strategy for NSCLC.

Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-ß/Smad signaling pathways.

Pancreatic ductal adenocarcinoma (PDA) is an aggressive type of malignant tumor with a poor prognosis and high mortality. Aberrant activation of hedgehog signaling plays a crucial role in the maintenance and progression of PDA. Here, we report that the dietary bioflavonoid quercetin has therapeutic potential for PDA by targeting sonic hedgehog (SHH) signaling. The effects of quercetin on the proliferation, apoptosis, migration, and invasion of pancreatic cancer cells (PCCs) and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Additionally, SHH signaling activity was determined. Quercetin significantly inhibited PCC proliferation by downregulating c-Myc expression. In addition, quercetin suppressed epithelial-mesenchymal transition (EMT) by reducing TGF-ß1 level, which resulted in inhibition of PCC migration and invasion. Moreover, quercetin induced PCC apoptosis through mitochondrial and death receptor pathways. In nude mouse models, PDA growth and metastasis were reduced by quercetin treatment. Mechanically, quercetin exerts its therapeutic effects on PDA by decreasing SHH activity. Interestingly, quercetin-induced SHH inactivation is mainly dependent on Gli2, but not Gli1. Enhance SHH activity by recombinant Shh protein abolished the quercetin-mediated inhibition of PCC proliferation, migration, and invasion. Furthermore, Shh activated TGF-ß1/Smad2/3 signaling and promoted EMT by inducing the expression of Zeb2 and Snail1 that eventually resulted in a partial reversal of quercetin-mediated inhibition of PCC migration and invasion. We conclude that quercetin inhibited the growth, migration, and invasion and induced apoptosis of PCCs by antagonizing SHH and TGF-ß/Smad signaling pathways. Thus, quercetin may be a potential candidate for PDA treatment.

A novel heterozygous carrier of ATP7B mutation with muscle weakness and tremor: A Chinese Case Report.

Wilson's disease (WD) is an autosomal recessive genetic disease linked to ATP7B, which is located on the chromosome 13q14.3. We presently report a hepatolenticular degeneration carrier whose clinical phenotype mainly included limb weakness and tremor with a novel WD mutation. The mutation in Exon 10 of ATP7B Gene [c.2480G>A p. (Arg827Gln)] was identified after gene sequencing. We have provided diagnostic analyses, such as muscle biopsy and electrophysiology, which would be helpful to deepen the understanding of the pathogenesis underneath nerve damage in WD heterozygote carriers (Hzc).