Abnormal expression of LCA and CD43 in SCLC: a rare case report and brief literature review.

BACKGROUND: To present an unusual case of abnormal LCA expression and CD43 in SCLC and to review the reported literature to avoid potential diagnostic pitfalls. CASE PRESENTATION: A 73-year-old male patient suffered from persistent back pain for more than one month. MRI revealed a compression fracture of the L1-L5 vertebra. A CT scan revealed multiple nodules and masses at the left root of the neck, lung hilum and mediastinum, and multiple areas of bony destruction of the ribs. Histology of the tumor revealed that small and round cells were arranged in nests with areas of necrosis. The tumor cells were round to ovoid with scant cytoplasm and indistinct cell borders. The nuclear chromatin was finely granular, and the nucleoli were absent or inconspicuous. Immunohistochemically, the tumor cells were positive for cytokeratin, TTF-1, POU2F3, LCA, and CD43. CONCLUSION: This report highlights a potential diagnostic pitfall in the diagnosis of SCLC, urges pathologists to exercise caution in cases of LCA and CD43 positivity and illustrates the need for further immunohistochemical studies to avoid misdiagnosis.

Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC.

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Association of composite dietary antioxidant index with prevalence of stroke: insights from NHANES 1999-2018.

Background: There is a growing acknowledgment of the potential influence of antioxidative effects resulting from dietary decisions on the occurrence of stroke. The objective of this study was to elucidate the correlation between the composite dietary antioxidant index (CDAI) and the incidence of stroke in the general population of the United States. Methods: We gathered cross-sectional data encompassing 40,320 participants from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Employing weighted multivariate logistic regression, we assessed the correlation between CDAI and stroke, while also investigating potential nonlinear relationships through restricted cubic spline (RCS) regression. Further, the intake of CDAI components were then incorporated into a predictive nomogram model, subsequently evaluated for its discriminatory prowess in stroke risk assessment using the receiver operating characteristic (ROC) curve. Results: Post-adjustment for confounding variables, we found that higher CDAI score were associated with a decreased risk of stroke, the odds ratio (OR) [95% CI] of CDAI associating with prevalence was 0.96 [0.94-0.98] (P< 0.001). Moreover, the adjusted OR [95% CI] for stroke across ascending CDAI quartiles stood at 0.90 [0.74-1.09], 0.74 [0.60-0.91], and 0.61 [0.50-0.76] compared to the reference quartile, respectively. The RCS analysis indicated a nonlinear yet negative correlation between CDAI and stroke. The nomogram model, constructed based the intake of antioxidants, exhibited a significant predictive capacity for stroke risk, boasting an area under the curve (AUC) of 77.4% (76.3%-78.5%). Conclusion: Our investigation ascertained a nonlinear negative relationship between CDAI and stroke within the broader American population. However, given the inherent limitations of the cross-sectional design, further comprehensive research is imperative to establish the causative nature of this association.

Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis.

OBJECTIVES: This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms. METHODS: Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy (TEM), Nanosight (NTA), and western blot. A mouse AS model was established, and exosomes were injected into the tail vein. Total cholesterol (TC) and triglycerides (TG) were detected using their corresponding assay kits. The contents of IL-1ß and IL-18 in serum were detected by ELISA. The mRNA and protein expression levels of GSDMD, Caspase1, and NLRP3 were detected by qRT-PCR and Western blot. Finally, aortic tissues in the Model and BMSC-EXO groups were sent for sequencing. RESULTS: TEM, NTA, and western blot indicated successful isolation of exosomes. Compared with the control group, the TC, TG contents, IL-1ß and IL-18 concentrations of the mice in the Model group were significantly increased; nonetheless, were significantly lower after injected with BMSC-EXO than those in the Model group (p < 0.05). Compared with the control group, the expressions of NLRP3, caspase-1 and GSDMD were significantly up-regulated in the Model group (p < 0.05), while the expressions of NLRP3, caspase-1, and GSDMD were significantly down-regulated by BMSC-EXO. By sequencing, a total of 3852 DEGs were identified between the Model and BMSC-EXO group and were significantly enriched in various biological processes and pathways related to mitochondrial function, metabolism, inflammation, and immune response. CONCLUSION: AS can induce pyroptosis, and BMSC-EXO can reduce inflammation and alleviate the progression of AS by inhibiting NLRP3/Caspase-1/GSDMD in the pyroptosis pathway.

Photocatalytic Ag/AgBr-MBG for Rapid Antibacterial and Wound Repair.

In daily life and during surgery, the skin, as the outermost organ of the human body, is easily damaged to form wounds. If the wound was infected by the bacteria, especially the drug-resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), it was difficult to recover. Therefore, it was important to develop the safe antimicrobial strategy to inhibit bacterial growth in the wound site, in particular, to overcome the problem of bacterial drug resistance. Here, the Ag/AgBr-loaded mesoporous bioactive glass (Ag/AgBr-MBG) was prepared, which had excellent photocatalytic properties under simulated daylight for rapid antibacterial activity within 15 min by generating reactive oxygen species (ROS). Meanwhile, the killing rate of Ag/AgBr-MBG against MRSA was 99.19% within 15 min, which further reduced the generation of drug-resistant bacteria. In addition, Ag/AgBr-MBG particles could disrupt bacterial cell membranes, showing the broad-spectrum antibacterial properties and promoting tissue regeneration and infected wound healing. Ag/AgBr-MBG particles might have potential applications as a light-driven antimicrobial agent in the field of biomaterials.

Head-to-head comparison of genotyping of human papillomavirus by real-time multiplex PCR assay using type-specific primers and SPF10-PCR-based line probe assay.

The SPF10-polymerase chain reaction (PCR)-based line probe assay (LiPA-25) with high analytical sensitivity and specificity for human papillomavirus (HPV) genotyping in clinical samples has been widely used in vaccine and epidemiologic studies. A real-time multiplex PCR assay using type-specific primers (Hybribio-23) with low workload and cost has been developed recently. The study aimed to compare the performance of LiPA-25 and Hybribio-23 in selected 1731 cervical swab and 117 tissue samples, with a focus on 20 common HPV types (14 high-risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68/73; 6 low-risk: 6, 11, 42, 43, 44, and 53). The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 1296 (74.9%) swab samples were identified as HPV-positive by Hybribio-23 or LiPA-25, of which 814 (62.8%) samples exhibited concordant, 358 (27.6%) showed additional or fewer types (compatible), and 124 (9.6%) were discordant. In addition, the two assays showed a perfect agreement for 20 HPV-combined detection (κ = 0.838) and 17 individual HPV types (all κ > 0.800), a good agreement for HPV31 (κ = 0.792) and 43 (κ = 0.696), and a moderate agreement for HPV42 (κ = 0.504). Hybribio-23 was significantly more sensitive for HPV58, 59, 68/73, 42, 43, and 44, and less sensitive for HPV35 and 66 than LiPA-25 (McNemar's test: all p < 0.05). For 117 HPV-positive tissue specimens, the identification of genotypes was 85.2% identical, 12.2% compatible, and only 2.6% discordant. The agreement for HPV31 (κ = 0.786), 68/73 (κ = 0.742), and HPV53 (κ = 0.742) was good, while for other types (all κ > 0.853) and 20 HPV-combined detection (κ = 0.936) was perfect (all p > 0.05). In conclusion, Hybribio-23 and LiPA-25 are comparable. Hybribio-23 could be used for the detection and genotyping of HPV in cervical samples for epidemiological and vaccine studies worldwide.

ß2-Microglobulin exacerbates neuroinflammation, brain damage, and cognitive impairment after stroke in rats.

ß2-Microglobulin (ß2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of ß2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of ß2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that ß2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit ß2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased ß2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by ß2M silencing. These findings suggest that ß2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Head-to-head comparison of genotyping of human papillomavirus by GP5+/6+-PCR-based reverse dot blot hybridization assay and SPF10-PCR-based line probe assay.

The SPF10-PCR-based line probe assay (LiPA-25) for human papillomavirus (HPV) genotyping with high analytical sensitivity and specificity was widely used in HPV vaccine clinical trials and epidemiologic studies. In the study, we aimed to compare a novel GP5+/6+-PCR-based reverse dot blot hybridization assay (Yaneng-23) with LiPA-25. The performance of two assays was evaluated in 1735 cervical swab and 117 tissue samples, with a focus on 19 common HPV types (14 high-risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68/73; 5 low-risk: 6, 11, 42, 43, and 53). A total of 1197 (69.0%) swab samples were identified as HPV-positive by two assays. Of these, 878 (73.4%) samples displayed absolute agreement (concordant), 255 (21.3%) showed additional or fewer types (compatible), and the remaining 64 (5.3%) samples were discordant. Additionally, the two assays showed an excellent strength of agreement for 19 HPV-combined detection (κ = 0.886) and 17 individual HPV types (all κ > 0.800), and displayed a good agreement for HPV39 (κ = 0.780) and 42 (κ = 0.699). Yaneng-23 was more sensitive than LiPA-25 for HPV58, 59, 68/73, 42, 43 and 53 (McNemar's test: all p < 0.05), while LiPA-25 was more sensitive for HPV31, 39, 52, and 66 than Yaneng-23 (all p < 0.05). In 113 HPV-positive tissue specimens, the identification of genotypes was 82.3% identical and 17.7% compatible. The agreement between the tests for HPV45 (κ = 0.796) and 51 (κ = 0.742) was good, and for other types (all κ > 0.843) and 19 HPV-combined detection (κ = 0.929) was perfect (all p > 0.05). In conclusion, Yaneng-23 and LiPA-25 are comparable. Yaneng-23 could be used for the detection and genotyping of HPV in cervical samples for epidemiological and vaccine studies worldwide.

Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer.

Integrin subunit alpha 3 (ITGA3) expression correlates with the development and prognosis of human cancers. This study aimed to investigate the association of ITGA3 expression with pancreatic cancer (PCa) prognosis. The ITGA3 gene expression data were extracted from The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) cohort and 14 Gene Expression Omnibus microarray datasets. The differences in ITGA3 expression levels between tumor and non-tumor tissues were compared using the Mann-Whitney U test. Cox regression analysis and meta-analysis were performed to detect the association of ITGA3 expression with PCa prognosis. ITGA3 expression was higher in tumors than in controls. Tumors with advanced grades (3/4) had higher ITGA3 levels compared with early-grade tumors (1/2). The meta-analysis of the TCGA PAAD cohort and seven microarray datasets (GSE28735, GSE62452, GSE79668, GSE71729, GSE57495, GSE78229, and GSE21501) showed that ITGA3 was a prognostic biomarker in PCa (hazard ratio (HR) = 1.38, 95% confidence interval (CI) 1.26-1.51, p < 0.00001). Five ITGA3-related genes, including ITGB1 (HR = 1.6), ITGB5 (HR = 1.6), ITGB6 (HR = 1.6), LAMA3 (HR = 2.1), and CD9 (HR = 2.3), correlated with PCa prognosis significantly (p < 0.05). Functional enrichment analysis showed that ITGA3 was related to "hsa04151: PI3K-Akt signaling pathway" and "hsa04510: Focal adhesion." We concluded that high ITGA3 expression was a potential prognostic biomarker in PCa.

Reoxygenation Modulates the Adverse Effects of Hypoxia on Wound Repair.

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Recent molecular design strategies for efficient photodynamic therapy and its synergistic therapy based on AIE photosensitizers.

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

ANTXR1 Regulates Erythroid Cell Proliferation and Differentiation through wnt/ß-Catenin Signaling Pathway In Vitro and in Hematopoietic Stem Cell.

Erythropoiesis is a highly complex and sophisticated multistage process regulated by many transcription factors, as well as noncoding RNAs. Anthrax toxin receptor 1 (ANTXR1) is a type I transmembrane protein that binds the anthrax toxin ligands and mediates the entry of its toxic part into cells. It also functions as a receptor for the Protective antigen (PA) of anthrax toxin, and mediates the entry of Edema factor (EF) and Lethal factor (LF) into the cytoplasm of target cells and exerts their toxicity. Previous research has shown that ANTXR1 inhibits the expression of γ-globin during the differentiation of erythroid cells. However, the effect on erythropoiesis from a cellular perspective has not been fully determined. This study examined the role of ANTXR1 on erythropoiesis using K562 and HUDEP-2 cell lines as well as cord blood CD34+ cells. Our study has shown that overexpression of ANTXR1 can positively regulate erythrocyte proliferation, as well as inhibit GATA1 and ALAS2 expression, differentiation, and apoptosis in K562 cells and hematopoietic stem cells. ANTXR1 knockdown inhibited proliferation, promoted GATA1 and ALAS2 expression, accelerated erythrocyte differentiation and apoptosis, and promoted erythrocyte maturation. Our study also showed that ANTXR1 may regulate the proliferation and differentiation of hematopoietic cells, though the Wnt/ß-catenin pathway, which may help to establish a possible therapeutic target for the treatment of blood disorders.

Bioinformatics analysis of KLF2 as a potential prognostic factor in ccRCC and association with epithelial-mesenchymal transition.

Clear cell renal cell carcinoma (ccRCC) is a primary pathological subtype of RCC and has poor clinical outcome. Krüppel-like factors (KLFs), which are zinc-finger proteins, may be involved in ccRCC development and progression. KLFs belong to the zinc-finger family of DNA-binding transcription factors and regulate transcription of downstream target genes. KLFs are involved in cancer development. The present study aimed to investigate the role of KLFs in ccRCC prognosis. The Cancer Genome Atlas database and multifactorial analysis showed that KLFs were widely expressed in pan-cancers and KLF2 was an independent protective factor for ccRCC prognosis. Patients with low KLF2 expression had a low survival probability and expression of KLF2 was downregulated in patients with ccRCC with high pathological grade (II + III vs. I). In addition, western blot and reverse transcription-quantitative PCR revealed that KLF2 was expressed at low levels in ccRCC cell lines and overexpression of KLF2 inhibited cell migration. In addition, KLF2 expression was negatively correlated with methylation. KLF2 expression was elevated following treatment of ccRCC cells with DNA methyltransferase inhibitor. A prognostic risk index prediction model was constructed based on multiple Cox regression. The receiver operating characteristic curve was 0.780 (area under curve >0.5). Furthermore, Gene Ontology enrichment analysis showed that 'cell adhesion' and 'junction' were negatively correlated with KLF2 and that high-risk group exhibited significantly activated 'epithelial-mesenchymal transition'. Western blot analysis showed that overexpression of KLF2 increased expression of E-cadherin, while decreasing levels of N-cadherin and vimentin. The present study highlighted the role of KLFs in ccRCC prognosis prediction and provides a research base for the search of validated prognostic biological markers for ccRCC.

Engineered Macrophage-Membrane-Coated Nanoparticles with Enhanced PD-1 Expression Induce Immunomodulation for a Synergistic and Targeted Antiglioblastoma Activity.

Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood-brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression (PD-1-MM@PLGA/RAPA). Using both in vitro and in vivo GBM models, we demonstrate that PD-1-MM@PLGA/RAPA can efficiently traverse across the BBB in response to the tumor microenvironment (TME) recruitment with nanoparticles accumulating at the tumor site. Furthermore, we show a boosted immune response as a result of enhancing CD8+ cytotoxic T-lymphocyte (CTL) infiltration. Together we provide a new nanoplatform for enhancing ICB in combination with conventional chemotherapy for GBM and many other cancers.

Exocyst controls exosome biogenesis via Rab11a.

Tumor cells actively release large quantities of exosomes, which pivotally participate in the regulation of cancer biology, including head and neck cancer (HNC). Exosome biogenesis and release are complex and elaborate processes that are considered to be similar to the process of exocyst-mediated vesicle delivery. By analyzing the expression of exocyst subunits and their role in patients with HNC, we aimed to identify exocyst and its functions in exosome biogenesis and investigate the molecular mechanisms underlying the regulation of exosome transport in HNC cells. We observed that exocysts were highly expressed in HNC cells and could promote exosome secretion in these cells. In addition, downregulation of exocyst expression inhibited HN4 cell proliferation by reducing exosome secretion. Interestingly, immunofluorescence and electron microscopy revealed the accumulation of multivesicular bodies (MVBs) after the knockdown of exocyst. Autophagy, the major pathway of exosome degradation, is not activated by this intracellular accumulation of MVBs, but these MVBs are consumed when autophagy is activated under the condition of cell starvation. Rab11a, a small GTPase that is involved in MVB fusion, also interacted with the exocyst. These findings suggest that the exocyst can regulate exosome biogenesis and participate in the malignant behavior of tumor cells.

Characteristics of serum metabolites in sporadic amyotrophic lateral sclerosis patients based on gas chromatography-mass spectrometry.

To identify differential metabolites and metabolic pathways and provide guidance for the novel biomarkers for diagnosis and prognosis of amyotrophic lateral sclerosis (ALS). ALS patients and people without nervous diseases were recruited. Metabolomic analysis was performed using gas chromatography-mass spectrometry (GC/MS). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst were used to identify metabolic pathways. 75 metabolites were detected and aligned. The OPLS-DA showed the metabolomic profile of ALS patients and those in the fast-progression and slow-progression ALS groups differed from that of CTRL (p < 0.05). The levels of maltose, glyceric acid, lactic acid, beta-alanine, phosphoric acid, glutamic acid, ethanolamine and glycine in ALS were significantly higher, while 2,4,6-tri-tert-butylbenzenethiol was lower. Glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, alanine, aspartate, and glutamate metabolism, beta-alanine metabolism, and pyruvate metabolism were significantly altered metabolic pathways in ALS. ROC was used to discriminate ALS from CTRL with an AUC of 0.898 (p < 0.001) using 2,4,6-tri-tert-butylbenzenethiol, beta-alanine, glycine, and ethanolamine. The serum metabolites and metabolic pathways in ALS patients are significantly altered compared with CTRL. These findings may contribute to the early diagnosis of ALS.

Prolonged oral ingestion of microplastics induced inflammation in the liver tissues of C57BL/6J mice through polarization of macrophages and increased infiltration of natural killer cells.

Microplastics (< 5 mm diameter) are one of most important environmental pollutants and contaminants worldwide. However, how microplastics affect liver immune microenvironment in not well understood. Microplastics (0.5 µm) were administered orally to C57BL/6J mice for 4 consecutive weeks at the rate of 0.5 mg/day. Non-parenchymal cells were isolated from of the mice through fractionation of fresh hepatic tissues. The immune landscape for four cell populations of B cells, T cells, NK cells and macrophages in the liver tissues was then evaluated using flow cytometry. The secretion level of inflammatory cytokines and associated signaling pathway were investigated using quantitative real-time polymerase chain reaction and western blot. Oral ingestion of microplastics increases liver weight, general liver index as well as expression of serum, liver function-related indicators. Microplastics also increased the infiltration of natural killer cells and macrophages to non-parenchymal liver cells, but reduced that of B cells to the same tissues. However, microplastics had no effect on the infiltration of T cell to non-parenchymal liver cells. Ingestion of MPs also up-regulated the expression of IFN-γ, TNF-α, IL-1ß, IL-6 and IL-33 mRNA, but down-regulated that of IL-4, IL-5, IL-10, IL-18 and TGF-ß1. Overall, the aforementioned processes were regulated via the NF-κB pathway in the hepatic non-parenchymal cells. Microplastics disrupts inflammatory process in liver tissues via the NF-κB signaling pathway. These findings provide a strong foundation on immune processes in hepatic tissues following prolonged ingestion of microplastics.

Prevalence and relevant factors of positive RF in brucellosis patients with arthralgia.

BACKGROUND: Brucellosis is a critical zoonotic disease in the world, it is the non-specific arthralgia that make brucellosis patients easily misdiagnosed as rheumatoid arthritis (RA) in endemic regions. Elevated rheumatoid factor (RF) is an essential indicator of RA, and the RF in brucellosis patients is significantly higher than healthy people. Therefore, this study further explored the distribution of RF and the relevant factors of the RF positivity in brucellosis patients with arthralgia, in order to strengthen the recognition of physicians for brucellosis patients with RF positivity, especially in brucellosis-endemic areas, so as to avoid misdiagnosis and untimely treatment that may lead to malignant outcomes. METHODOLOGY AND PRINCIPAL FINDINGS: The medical records of all 572 brucellosis inpatients were collected in the Sixth People's Hospital of Shenyang, China from 2015 to 2016. After excluding 106 patients without arthralgia, 5 patients who unwilling to perform RF testing and 16 patients with diseases that may affect RF, 445 brucellosis inpatients with arthralgia were involved in this retrospective cross-sectional study. 143 (32.1%) patients with RF >10 IU/ml were classified into the RF positive group, with an average level of 16.5[12.2, 34.7] IU/ml, of which 45 (10.1%) patients were high-positive with RF >30 IU/ml. Multivariate logistic regression model was used to further analyze the relevant factors of the RF positivity and found that age, wrist joint pain and elevated C-reactive protein (CRP) were positively associated with RF positivity, with OR of 1.02 (P = 0.024), 8.94 (P = 0.008) and 1.79 (P = 0.019), respectively. CONCLUSION: The prevalence of positive RF in brucellosis patients with arthralgia was critical, nearly one-third of patients had RF positive. Elderly men brucellosis patients with arthralgia, wrist joint pain and elevated CRP were at high risk of positive RF. It is reminded that physicians should focus on differential diagnosis during clinical diagnosis and treatment, especially in brucellosis-endemic regions.

Naturally acquired HPV antibodies against subsequent homotypic infection: A large-scale prospective cohort study.

BACKGROUND: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously. METHODS: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model. FINDINGS: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83). INTERPRETATION: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection. FUNDING: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax.

Phagocytosis of polymeric nanoparticles aided activation of macrophages to increase atherosclerotic plaques in ApoE-/- mice.

The unique physiochemical properties of nanomaterials have been widely used in drug delivery systems and diagnostic contrast agents. The safety issues of biomaterials with exceptional biocompatibility and hemo-compatibility have also received extensive attention at the nanoscale, especially in cardiovascular disease. Therefore, we conducted a study of the effects of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) on the development of aortic atherosclerotic plaques in ApoE-/- mice. The particle size of PLGA NPs was 92.69 ± 3.1 nm and the zeta potential were - 31.6 ± 2.8 mV, with good blood compatibility. ApoE-/- mice were continuously injected with PLGA NPs intravenously for 4 and 12 weeks. Examination of oil red O stained aortic sinuses confirmed that the accumulation of PLGA NPs caused a significantly higher extension of atherosclerotic plaques and increasing the expression of associated inflammatory factors, such as TNF-α and IL-6. The combined exposure of ox-LDL and PLGA NPs accelerated the conversion of macrophages to foam cells. Our results highlight further understanding the interaction between PLGA NPs and the atherosclerotic plaques, which we should consider in future nanomaterial design and pay more attention to the process of using nano-medicines on cardiovascular diseases.