JAM2 is a prognostic biomarker and inhibits proliferation, metastasis and epithelial-mesenchymal transition in lung adenocarcinoma.

BACKGROUND: Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear. METHODS: In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real-time quantitative PCR, western blot and immunohistochemistry. Additionally, in vitro experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial-mesenchymal transition. Furthermore, we established a xenograft model to investigate the in vivo effects of JAM2 on tumorigenesis. RESULTS: Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial-mesenchymal transition. Additionally, in vivo experiments confirmed that JAM2 overexpression led to a reduction in tumor growth. CONCLUSION: Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients.

[Transurethral enucleation plus pneumo-cystostomy rotary cut for large benign prostatic hyperplasia].

OBJECTIVE: To investigate the feasibility, effectiveness and practicability of transurethral enucleation plus pneumocystostomy rotary cut (TUE + PCRC) for large benign prostatic hyperplasia (BPH). METHODS: We performed TUE + PCRC for 26 BPH patients aged 62 - 85 years with the prostate volume of 80 - 165 ml. We conducted transurethral enucleation of the hyperplastic prostate glands and pushed them into the bladder, followed by bladder puncture for pneumo-cystostomy rotary cut. RESULTS: All the surgical procedures were successfully accomplished, with the mean surgical time of 41 (32 - 54) minutes and intraoperative blood loss < 60 ml in all the cases. Twenty-three of the patients were followed up for 2 - 8 months, which revealed no stricture of the urethra or any other severe complications. Compared with the preoperative baseline, significant improvement was achieved in the IPSS (6.5 +/- 2.2 vs 26.2 +/- 2.4), QOL (1.4 +/- 0.9 vs 4.6 +/- 1.2) and Qmax ([5.8 +/- 1.0 ] vs [19.6 +/- 2.8] ml/s) of the patients after surgery (P < 0.01). CONCLUSION: TUE + PCRC, with its advantages of short operation time and less severe complications, is a safe and effective approach to the management of large BPH.

TESC acts as a prognostic factor and promotes epithelial-mesenchymal transition progression in esophageal squamous carcinoma.

BACKGROUND: Tescalcin (TESC) is a critical regulator of cell differentiation and growth, promoting malignant progression in various tumors. However, the role of TESC in esophageal squamous carcinoma (ESCC) remains unclear. METHODS: Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were utilized to identify the difference in TESC expression between ESCC tissues and normal tissues adjacent to the carcinoma. The relationship between TESC and several clinicopathological features was shown by the chi-square test. Log-rank analysis and Cox regression were used to detect the relationship between TESC and the prognosis in ESCC. Clone formation and cell count kit-8 (CCK-8) were applied to detect the impact of TESC on ESCC proliferation. Wound healing assay and transwell assay were used to confirm the influence of TESC on the invasion and migration. Spearman correlation coefficient was used to describe the correlation between TESC and epithelial-mesenchymal transition (EMT)-related protein expression in ESCC. Western blot was used to detect the effect of TESC on the expression of E-cadherin, N-cadherin, and Vimentin as well as AKT signaling pathway. Xenograft tumors were developed to test the pro-tumorigenic impacts of TESC in vivo. RESULTS: TESC was upregulated expression in ESCC tissues and was linked to poorer prognosis and worse tumor infiltration, TNM stage, and lymph node metastasis. Meanwhile, TESC was able to act as an independent prognostic factor in ESCC. TESC promoted tumor cell proliferation, invasion, migration, EMT progression, and activated the phosphorylation of the AKT pathway. Furthermore, TESC knockdown inhibited the growth of carcinoma in vivo. CONCLUSION: TESC is a predictive factor for poor prognosis in ESCC and may provide a new strategy for ESCC treatment.

Monoclonal Antibody Targeting CGRP Relieves Cisplatin-Induced Neuropathic Pain by Attenuating Neuroinflammation.

Chemotherapy-induced neuropathic pain (CIPN) is a common side effect of antitumor chemotherapeutic agents. It describes a pathological state of pain related to the cumulative dosage of the drug, significantly limiting the efficacy of antitumor treatment. Sofas strategies alleviating CIPN still lack. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in many pathologic pains. In this study, we explored the effects of CGRP blocking on CIPN and potential mechanisms. Total dose of 20.7 mg/kg cisplatin was used to establish a CIPN mouse model. Mechanical and thermal hypersensitivity was measured using von Frey hairs and tail flick test. Western blot and immunofluorescence were utilized to evaluate the levels of CGRP and activated astrocytes in mouse spinal cord, respectively. In addition, real-time quantitative PCR (RT-qPCR) was used to detect the level of inflammatory cytokines such as IL-6, IL-1ß, and NLRP3 in vitro and in vivo. There are markedly increased CGRP expression and astrocyte activation in the spinal cord of mice following cisplatin treatment. Pretreatment with a monoclonal antibody targeting CGRP (ZR8 mAb) effectively reduced cisplatin-induced mechanical hypersensitivity and thermal nociceptive sensitization and attenuated neuroinflammation as marked by downregulated expression of IL-6, IL-1ß, and NLRP3 in the mice spinal cord and spleen. Lastly, ZR8 mAb does not interfere with the antitumor effects of cisplatin in tumor-bearing mice. Our findings indicate that neutralizing CGRP with monoclonal antibody could effectively alleviate CIPN by attenuating neuroinflammation. CGRP is a promising therapeutic target for CIPN.

Modulating Electron Transfer between Pt and MOF Support through Pd Doping Promotes Nanozyme Catalytic Efficiency.

Electron transfer is considered to be a typical parameter that affects the catalytic activity of nanozymes. However, there is still controversy regarding whether higher or lower electron transfer numbers are beneficial for improving the catalytic activity of nanozymes. To address this issue, we propose the introduction of Pd doping as an important electron regulation strategy to tune electron transfer between Pt and ZIF-8 carriers (PtxPd1@ZIF-8). We observe a volcano-shaped relationship between the electron transfer number and catalytic activity, reaching its peak at Pt4Pd1@ZIF-8. Mechanism studies indicate that as the electron transfer number from Pt to ZIF-8 carriers increases, the d-band center of the active site Pt increases, reducing the occupancy of antibonding states and enhancing the adsorption capacity of the key intermediate (*O). However, a further increase in the adsorption of *O energy makes it difficult to desorb and participate in the next reaction, thus exhibiting volcanic activity. The optimized Pt4Pd1@ZIF-8 nanozyme is applied to develop an immunoassay for the detection of zearalenone, achieving a detection limit of 0.01 µg/L, which is 6 times higher than that of the traditional enzyme-linked immunosorbent assay. This work not only reveals the potential regulatory mechanism of electron transfer on the catalytic activity of nanozymes but also improves the performance of nanozyme-based biosensors.

Tumor associated macrophages in esophageal squamous carcinoma: Promising therapeutic implications.

Esophageal squamous carcinoma (ESCC) is a prevalent and highly lethal malignant tumor, with a five-year survival rate of approximately 20 %. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising over 50 % of the tumor volume. TAMs can be polarized into two distinct phenotypes, M1-type and M2-type, through interactions with cancer cells. M2-type TAMs are more abundant than M1-type TAMs in the TME, contributing to tumor progression, such as tumor cell survival and the construction of an immunosuppressive environment. This review focuses on the role of TAMs in ESCC, including their polarization, impact on tumor proliferation, angiogenesis, invasion, migration, therapy resistance, and immunosuppression. In addition, we discuss the potential of targeting TAMs for clinical therapy in ESCC. A thorough comprehension of the molecular biology about TAMs is essential for the development of innovative therapeutic strategies to treat ESCC.

Identification and experimental verification of an anoikis and immune related signature in prognosis for lung adenocarcinoma.

Background: Both metastasis and immune resistance are huge obstacle in lung adenocarcinoma (LUAD) treatment. Multiple studies have shown that the ability of tumor cells to resist anoikis is closely related to the metastasis of tumor cells. Methods: In this study, the risk prognosis signature related to anoikis and immune related genes (AIRGs) was constructed by cluster analysis and the least absolute shrinkage and selection operator (LASSO) regression by using The Cancer Genome Atlas (TCGA) Program and the Gene Expression Omnibus (GEO) database. Kaplan-Meier (K-M) curve described the prognosis in the different groups. Receiver operating characteristic (ROC) was applied to evaluate the sensitivity of this signature. Principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), independent prognostic analysis, and nomogram were utilized to assess the validity of the signature. In addition, we used multiple bioinformatic tools to analyze the function between different groups. Finally, mRNA levels were analyzed by quantitative real-time PCR (qRT-PCR). Results: The K-M curve showed a worse prognosis for the high-risk group compared to that for the low-risk group. ROC, PCA, t-SNE, independent prognostic analysis and nomogram showed well predictive capabilities. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that differential genes were mainly enriched in immunity, metabolism, and cell cycle. In addition, multiple immune cells and targeted drugs differed in the two risk groups. Finally, we found that the mRNA levels of AIRGs were remarkably different in normal versus cancer cells. Conclusions: In short, we established a new model about anoikis and immune, which can well predict prognosis and immune response.

The biology of VSIG4: Implications for the treatment of immune-mediated inflammatory diseases and cancer.

V-set and immunoglobulin domain containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. VSIG4 maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation, thereby inhibiting the development of immune-mediated inflammatory diseases but enhancing cancer progression. Consequently, VSIG4 exhibits a potential therapeutic effect for immune-mediated inflammatory diseases, but also is regarded as a novel target of immune checkpoint inhibition in cancer therapy. Recently, soluble VSIG4, the extracellular domain of VSIG4, shed from the surface of macrophages, has been found to be a biomarker to define macrophage activation-related diseases. This review mainly summarizes recent new findings of VSIG4 in macrophage phagocytosis and immune homeostasis, and discusses its potential diagnostic and therapeutic usage in infection, inflammation, and cancer.

FAM107A as a tumor suppressor in esophageal squamous carcinoma inhibits growth and metastasis.

BACKGROUND: Sequence similarity Family 107 member A (FAM107A) has been recognized as a tumor suppressor of various malignancies, which suppresses tumor proliferation and metastasis. Its specific role in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: Public datasets including Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO), quantitative real-time PCR (qRT-PCR), and Western blot were utilized for comparative analysis of FAM107A expression between ESCC and normal tissues. The link between FAM107A and clinicopathological features, as well as prognosis determined through χ2-test, log-rank analysis, and univariate and multivariate analyses, respectively. The impact of FAM107A on ESCC cell malignant behavior was confirmed through in vitro assays, including cell counting using the Cell Counting Kit-8 (CCK-8), clonal formation, wound healing, and transwell assays. Western blot analysis was employed to assess the effects of FAM107A on tumor epithelial-mesenchymal transition (EMT) and cell cycle-related proteins. Finally, xenograft tumors were developed to investigate the influence of FAM107A on ESCC growth in vivo. RESULTS: FAM107A exhibited low expression in ESCC tissues. Reduced FAM107A expression was associated with a poorer prognosis and unfavorable clinicopathological characteristics, such as degree of differentiation, T-stage, and N-stage. Overexpression of FAM107A suppressed ESCC cell proliferation, invasion, migration, the EMT process, and cell cycle progression. Finally, FAM107A overexpression inhibited tumor development in vivo. CONCLUSION: The decreased expression of FAM107A is indicative of a worse prognosis for ESCC patients. FAM107A exerts inhibitory impacts on malignant behavior and may hold promise as a therapeutic target for ESCC.

[Transcriptional Modification and Potential Intracellular Signaling Mechanisms in Human Macrophages Primed by Interferon-γ].

OBJECTIVE: To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms. METHODS: RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms. RESULTS: RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene. CONCLUSION: Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.

Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress.

Silibinin is a flavonoid extracted from the medicinal plant Silybum marianum (milk thistle), traditionally used to treat liver disease. Recent studies have shown that the antioxidative stress and anti-inflammatory effects of milk thistle are used in the treatment of neurological diseases. Silibinin has antioxidative stress and antiapoptotic effects and reduces cognitive impairment in models of Alzheimer's disease (AD). However, the underlying mechanism of silibinin related to improvement of cognition remains poorly understood. In this study, we used the model of lateral ventricle injection of formaldehyde to examine the related mechanism of silibinin in improving cognitive impairment disorders. Oral administration of silibinin for three weeks significantly attenuated the cognitive deficits of formaldehyde-induced mice in a Y-maze test and Morris water maze test. Y-maze results show that silibinin increases the rate of spontaneous response alternation in FA-induced mice. Silibinin increases the target quadrant spending time and decreases escape latency in the Morris water maze test. We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein expression of NRF2 in the hippocampus. Well, silibinin reduces the content of DHE and decreases the levels of apoptosis of mature neuron cells. We investigated the effect of silibinin on the content of formaldehyde degrading enzymes; biochemical analyses revealed that silibinin increased GSH and ALDH2 in formaldehyde-induced mice. In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. Silibinin inhibits the expression of GSK-3ß in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3ß. Based on our findings, we verified that the mechanism of silibinin improving cognitive impairment may be antioxidative stress, and silibinin is one of the potentially promising drugs to prevent formaldehyde-induced cognitive impairment.

H2S Regulation of Metabolism in Cucumber in Response to Salt-Stress Through Transcriptome and Proteome Analysis.

In a previous study, we found that H2S alleviates salinity stress in cucumber by maintaining the Na+/K+ balance and by regulating H2S metabolism and the oxidative stress response. However, little is known about the molecular mechanisms behind H2S-regulated salt-stress tolerance in cucumber. Here, an integrated transcriptomic and proteomic analysis based on RNA-seq and 2-DE was used to investigate the global mechanism underlying H2S-regulated salt-stress tolerance. In total, 11,761 differentially expressed genes (DEGs) and 61 differentially expressed proteins (DEPs) were identified. Analysis of the pathways associated with the DEGs showed that salt stress enriched expression of genes in primary and energy metabolism, such as photosynthesis, carbon metabolism and biosynthesis of amino acids. Application of H2S significantly decreased these DEGs but enriched DEGs related to plant-pathogen interaction, sulfur-containing metabolism, cell defense, and signal transduction pathways. Notably, changes related to sulfur-containing metabolism and cell defense were also observed through proteome analysis, such as Cysteine synthase 1, Glutathione S-transferase U25-like, Protein disulfide-isomerase, and Peroxidase 2. We present the first global analysis of the mechanism underlying H2S regulation of salt-stress tolerance in cucumber through tracking changes in the expression of specific proteins and genes.

[X-ray guided internal urethroplasty with PlasmaKinetic electrodes for urethratresia].

OBJECTIVE: To evaluate endourethral surgery for urethratresia under the X-ray guide. METHODS: We performed transurethral urethroplasty for 11 patients with urethratresia using the PlasmaKinetic electrodes under the guidance of C arm xanthippe. RESULTS: In the 11 cases, operations were all successful, 9 achieved smooth urination and 2 needed regular urethral dilation. CONCLUSION: X-ray guided internal urethroplasty with PlasmaKinetic electrodes is a simple and efficient treatment for urethratresia.

[Progress in Newcastle disease virus against tumor].

Newcastle disease virus is paramyxoviridae, Avian mumps virus genus type I, and infects more than 250 species of birds, causing huge losses on poultry farming worldwide. Numerous experiments have demonstrated that Newcastle disease virus has oncolytic activity on tumor cells and can selectively replicate in cancer cells. Thus, Newcastle disease virus is a potential therapeutic agent for cancer treatment. Some human clinical trials achieved good results. In this review, we summarized research progress of the relationship between the structural protein of Newcastle disease virus and virulence, anti-tumor and autophagy of Newcastle disease.