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Macrophages play a crucial role in malignant pleural effusion (MPE), a frequent complication of advanced cancer. While C1q + macrophages have been identified as a pro-tumoral cluster, direct evidence supporting the role of C1q-mediated macrophages remains to be elucidated. This study employed global and macrophage-specific knockout mice to investigate the role of C1q in MPE. The data demonstrated that C1q deficiency in macrophages suppressed MPE and prolonged mouse survival. scRNA-seq analysis of the C1qa -/- mouse MPE model revealed that C1q deficiency significantly decreased the proportion of M2 macrophages in MPE. In vitro experiments suggested that C1q expression was gradually upregulated during M2 polarization, which was C1q-dependent, as was antigen presentation. Deficiency of C1q in macrophages rescued the exhausted status of CD8 + T cells and enhanced the immune activity of CD8 + T cells and NK cells in both MPE and pleural tumors. Cell-to-cell interaction analysis demonstrated that C1q deficiency attenuated the immunoinhibitory effects of macrophages on NK cells by downregulating the CCR2-CCL2 signaling axis. Metabolomic analysis revealed significantly elevated hippuric acid levels in C1q-deficient mouse MPE. Treatment with either hippuric acid or a CCR2 antagonist inhibited MPE and tumor growth, with an even more pronounced effect observed when both treatments were combined., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Interleukin-10 (IL-10) promotes the formation and development of malignant pleural effusion (MPE). Previous studies have elucidated the pathogenesis from the view of the immune-regulation function of CD4 + T-cells. However, the underlying mechanism is still not fully understood. In this study, our results showed that IL-10 deficiency reduced the percentage of macrophages in mouse MPE and regulated M1/M2 polarization in vivo and in vitro . The migration capacity of tumor cells was suppressed, and apoptosis was promoted when tumor cells were cocultured with MPE macrophages in the absence of IL-10. Messenger RNA sequencing of MPE macrophages showed that S100A9 was downregulated in IL-10 -/- mice. Bone marrow-derived macrophages obtained from wild-type mice transfected with S100A9-specific small interfering RNAs (siRNAs) also showed less M2 and more M1 polarization than those from the siRNA control group. Furthermore, downregulation of S100A9 using S100A9-specific siRNA suppressed MPE development, decreased macrophages, and modulated macrophage polarization in MPE in vivo . In conclusion, S100A9 plays a vital role in the process of IL-10 deficiency-mediated MPE suppression by regulating M1/M2 polarization, thus influencing the tumor-migration capacity and apoptosis. This could result in clinically applicable strategies to inhibit the formation of MPE by regulating the polarization of MPE macrophages., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Xue-Bin Pei et al.)

Antimony (Sb) in PM 2.5 has attracted close attention as a new air pollutant due to its extensive use in daily life. The identification of antimony sources in PM 2.5 by scientific methods is important to control its pollution. In this study, the Sb and other elements concentrations and Pb isotopic compositions in PM 2.5 and possible pollution sources (soil, road dust, traffic emission, coal-fired fly ash, local factory emission dust and cement dust) were analyzed. The results showed that the Sb in the PM 2.5 samples had seasonal change. The enrichment factors of Sb in PM 2.5 samples were all above 100 in four seasons, which indicated anthropogenic pollution. The average value of potential ecological risk index was at extremely high-risk level greater than 320. Based on Pearson correlation coefficient and hierarchical cluster analysis results, the pollution sources of antimony and lead in PM 2.5 samples were highly consistent which means that Pb isotopes might be a new and feasible tracer for Sb pollution in air. The sources analysis results based on Pb isotopes indicated that the proportion of Pb and Sb from coal-fired fly ash was the highest in winter (47.7%) and inclined to road dust in spring (34.5%), but it was mainly from traffic emissions in summer and autumn (34.2% and 32.8%). This study showed that Pb isotope tracing can be applied to predict the potential pollution sources, and it was also a feasible substitute for tracing Sb pollution in PM 2.5 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The detection of interleukin 33 (IL-33) in pleural effusion may be more sensitive in diagnosing tuberculous pleural effusion (TPE). The present study aimed to assess the accuracy of pleural IL-33 for the diagnosis of TPE by means of meta-analysis and systematic review of relevant studies., Method: After retrieving the published studies, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and a summary receiver operating characteristic curve were assessed to estimate the usefulness of pleural IL-33 in diagnosing TPE using meta-analysis with a random-effects model. We also performed meta-regression and subgroup analysis., Results: A total of 639 patients from 6 studies were analyzed. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.87 (95% confidence interval [CI], 0.82-0.91), 0.76 (95% CI, 0.72-0.80), 6.54 (95% CI, 2.65-16.15), 0.17 (95% CI, 0.10-1.27), and 45.40 (95% CI, 12.83-160.70) respectively. The area under the curve was 0.94. The composition of the included population was the main cause of heterogeneity and subgroup analysis showed that pleural IL-33 had a higher specificity (0.93, 95% CI 0.87-0.96) when used for differential diagnosis between TPE and malignant pleural effusion., Conclusion: The detection of IL-33 alone in pleural effusion seems to not be an efficient diagnostic marker for TPE but may serve as a novel biomarker to differentiate between TPE and malignant pleural effusion., Competing Interests: No potential conflicts of interest relevant to this article were reported. The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Malignant pleural effusion (MPE) is a common medical problem caused by multiple malignancies, especially lung cancers, and always comes along with a poor outcome. Early detection and diagnosis are important for improving the prognosis in patients with MPE. Salivary microRNAs (miRNAs) may represent a relatively convenient way for diagnosing MPE. We investigated the characteristics of salivary miRNAs of MPE patients, benign pleural effusion (BPE) patients, patients with a malignant tumor but without pleural effusion (MT), and healthy controls (HCs). We believe that they may show potential as a non-invasive and convenient biomarker for diagnosing MPE., Methods: From January 1, 2019, to July 1, 2019, 57 MPE patients, 33 BPE patients, 50 MT patients, and 49 HCs were enrolled. To select candidate biomarkers, in the discovery phase, the salivary miRNA profiles were detected in three MPE patients and three HCs. Then, qPCR was used in the validation phase with 54 MPE patients, 33 BPE patients, 50 MT patients, and 46 HCs to assay the selected miRNAs., Results: hsa- miR-4484 and hsa- miR-3663-3p were identified as potential biomarkers to diagnose MPE patients, with areas under the curve (AUC) of 0.768 and 0.666, respectively. The diagnostic efficacy was higher when the combination of both miRNAs was used, with an AUC of 0.802. No correlation was found between the volume of MPE and the expression of salivary miRNAs., Conclusions: This study reports the characterization of salivary miRNAs collected from MPE patients. A combination of hsa- miR-4484 and hsa- miR-3663-3p showed potential discriminatory power for MPE detection, and it may be helpful for the early diagnosis of MPE, i.e., before the pleural effusion volume is too large., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-530). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN-γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ-induced beta cells destruction remains unclear. In this study, we used the murine beta cell line MIN6 and primary islet cells as models for investigating the underlying cellular mechanisms involved in LIGHT/IFNγ - induced pancreatic beta cell destruction. LIGHT and IFN-γ synergistically reduced MIN6 and primary islet cells viability; decreased cell viability was due to apoptosis, as demonstrated by a significant increase in Annexin V(+) cell percentage, detected by flow cytometry. In addition to marked increases in cytochrome c release and NF-κB activation, the combination of LIGHT and IFN-γ caused an obvious decrease in expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, but an increase in expression of the pro-apoptotic proteins Bak and Bax in MIN6 cells. Accordingly, LIGHT deficiency led to a decrease in NF-κB activation and Bak expression, and peri-insulitis in non-obese diabetes mice. Inhibition of NF-κB activation with the specific NF-κB inhibitor, PDTC (pyrrolidine dithiocarbamate), reversed Bcl-xL down-regulation and Bax up-regulation, and led to a significant increase in LIGHT- and IFN-γ-treated cell viability. Moreover, cleaved caspase-9, -3, and PARP (poly (ADP-ribose) polymerase) were observed after LIGHT and IFN-γ treatment. Pretreatment with caspase inhibitors remarkably attenuated LIGHT- and IFNγ-induced cell apoptosis. Taken together, our results indicate that LIGHT signalling pathway combined with IFN-γ induces beta cells apoptosis via an NF-κB/Bcl2-dependent mitochondrial pathway., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: The objective of this study is to detect HMGA2 expression in renal carcinoma to explore its relationship with clinicopathology and its significance in prognosis., Methods: Expressions of HMGA2 mRNA and protein were detected in 50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples and 40 renal benign tumour specimens via reverse transcription polymerase chain reaction and immunohistochemical assay. Expression analysis was performed along with clinical data analysis., Results: The relative expression levels of HMGA2 mRNA in renal carcinoma, renal benign tumour tissues and adjacent normal renal tissues were 0.84±0.23, 0.19±0.06 and 0.08±0.04, respectively. HMGA2 protein positive rates were 68.0%, 7.5% and 2.0%, with a significant difference ( P <0.05). HMGA2 expression was not significantly correlated with gender, age, tumour size and histological type ( P >0.05), but was significantly correlated with TNM stages and lymph node metastasis ( P <0.05)., Conclusions: The expressions of HMGA2 gene and protein in renal carcinoma were closely correlated with tumour formation, progression and metastasis. HMGA2 may become a powerful new pathological marker and prognostic factor for renal carcinoma.

Background: Altered expression of astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression. The present study aimed to investigate the clinical and prognostic significance of AEG-1 expression in pancreatic ductal adenocarcinoma (PDAC)., Methods: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were employed to assess AEG-1 expression in three pancreatic cancer cell lines and normal pancreatic duct epithelial cells. qRT-PCR and immunohistochemical analyses were performed to detect AEG-1 expression in ten pairs of PDAC and normal pancreas tissues. Immunohistochemistry was then used to examine AEG-1 expression in paraffin-embedded tissues obtained from 105 patients, and its association with clinicopathological parameters including cancer classification was examined. Kaplan-Meier analysis was performed to study the survival rates of patients., Results: Expression of AEG-1 mRNA and protein was markedly higher in pancreatic cancer cell lines than that in the normal pancreatic duct epithelial cells. AEG-1 expression was evidently upregulated in PDAC tissues compared to that of the matched distant normal pancreas tissues. qRT-PCR data revealed that the tumor/non-tumor ratio of AEG-1 expression was >1.5-fold (up to 6.5-fold). Immunohistochemical data showed that AEG-1 protein was detected in 98.09% (103/105) of PDAC tissues; and they were found to be associated with tumor size (P = 0.025), advanced clinical stage (P = 0.004), T classification (P = 0.006), N classification (P = 0.003), and M classification (P = 0.007). Furthermore, Kaplan-Meier analysis showed that patients with high AEG-1-expressed PDAC had shorter overall survival. A multivariate Cox regression analysis revealed that clinical stage, T classification, and AEG-1 expression were the independent prognostic predictors for PDAC., Conclusions: This study suggests that AEG-1 protein was highly expressed in PDAC and associated with poor prognosis of the patients.

Objective: To analyze the trend of the incidence of prostate cancer in urban Tianjin area between 1981 and 2004 so as to provide scientific rationales for the prevention and control of prostate cancer., Methods: The data of prostate cancer cases were provided by the Tianjin Cancer Registry. The SAS system V9 was used to calculate the crude incidence, age-adjusted incidence and age specific incidence of prostate cancer in Tianjin between 1981 and 2004. And the Join point 3.0 software was used to analyze secular trends., Results: Between 1981 and 2004, a total of 1060 prostate cancer cases were diagnosed in Tianjin. And the age-adjusted incidence rate was 2.84/100 000 in 2004. The incidence of prostate cancer showed 3 incremental stages during the 24-year period at an annual average of 4.02%. An aging trend was observed for prostate cancer patients. The elder patients had a faster increment in incidence. Specifically, it increased annually at 4.63% for age group 65 - 74 year versus 5.18% for age group 75 years or more., Conclusion: Despite a low incidence of prostate cancer in Tianjin, it is increasing at a fast rate. The prevention and control of prostate cancer should be strengthened.

Aim: To investigate the immunomodulatory effects of andrographolide on both innate and adaptive immune responses., Methods: Andrographolide (10 microg/mL in vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface antigen expression was evaluated by flow cytometry, whereas phosphorylation level of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg specific IL-4-producing splenocyte was enumerated by ELISPOT., Results: Andrographolide treatment in vitro attenuated either LPS or IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody production and the number of IL-4-producing splenocytes were reduced by in vivo administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and AKT were observed in macrophages treated with andrographolide., Conclusion: Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signaling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization.

The title Cd(II) coordination polymer, catena-poly[[{1,4-bis-[1-(2-pyridylmeth-yl)benzimidazol-2-yl]butane}cadmium(II)]-μ-benzene-1,3-dicarboxyl-ato], [Cd(C(8)H(4)O(4))(C(30)H(28)N(6))](n), was obtained by reaction of CdCO(3), benzene-1,3-dicarboxylic acid (H(2)btc) and 1,4-bis-[1-(2-pyridylmeth-yl)benzimidazol-2-yl]butane (L). The Cd(II) cation is six-coordinated by an N(2)O(4)-donor set. L acts as a bidentate ligand and btc anions link Cd(II) centers into a chain propagating parallel to [010].

Aim: To test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for improving the immune responses induced by hepatitis B virus core gene DNA vaccine., Methods: We used RT-PCR based strategies to develop IL-15 expression constructs. We first confirmed that the gene could be expressed in Escherichia coli due to the poor expression of IL-15. Then the bioactivity of IL-15 plasmid expression product was identified by CTLL-2 proliferation assay. One hundred micrograms of DNA from each of the IL-15 eukaryotic expressed plasmid and the recombinant plasmid harboring DNA encoding the 144 amino acids of the N-terminus of HBV core gene (abbreviated pHBc144) was used to co-immunize C57 BL/6 mice. The titer of anti-HBcIgG was detected by ELISA and the antigen-specific CD8(+) T cells (CD8(+)IFN-gamma(+) T cells) were detected by intracellular cytokine staining at different time points., Results: After co-immunization by pIL-15 and pHBc144 DNA vaccine the antigen-specific CD8(+) cells of mice increased gradually, the first peak of immune response appeared 14 d later, then the number of antigen-specific CD8(+) Ts cells decreased gradually and maintained at a steady level in 3 mo. After boosting, the number of antigen-specific CD8(+) T cells reached the second peak 10 d later with a double of the 1st peak, then the number of antigen-specific CD8(+) T cells decreased slowly. IL-15 as a gene adjuvant had no significant effect on humoral immune responses induced by hepatitis B virus core gene DNA vaccine, but increased the memory antigen-specific CD8(+) T cells induced by hepatitis B virus core gene DNA vaccine., Conclusion: DNA vaccine constructed by HBc Ag 1-144 amino acid induces effective cell immunity, and cytokine plasmid-delivered IL-15 enhances the longevity of CD8(+) T cells.