Global overview of anterior cruciate ligament reconstruction in children and adolescents over the past 20 years: a bibliometric analysis.

OBJECTIVES: The objectives of this paper is to conduct a bibliometric analysis to examine the research status and development trend of anterior cruciate ligament injury and reconstruction in children and adolescents over the past 20 years. DESIGN: Descriptive Research. METHODS: This study obtained information regarding studies on Anterior Cruciate Ligament Reconstruction in Children and Adolescents from the Web of Science Core Collection database. Visual and bibliometric analysis were conducted using VOSviewer, Origin 2022, Pajek64 5.18and Excel 2019. These analytic tools facilitated the analysis of various aspects, including countries/regions, institutions, authors, journals and keywords related to the research. RESULTS: From 2003 to 2023, a total of 1328 articles were retrieved in WOS, and 637 articles were selected by two authors. The most productive institutions are Childrens Hosp Philadelphia, Kocher, ms. Their articles have the highest number of publications and citations. The American journal of sports medicine is the most frequently cited journal for articles on anterior cruciate ligament reconstruction in children and adolescents. The most common keywords used in these articles were "anterior cruciate ligament reconstruction", "injury, children, adolescent", and "skeletally immature patients". CONCLUSIONS: This study provides valuable insights into the research focus of anterior cruciate ligament reconstruction in children and adolescents. In recent years, there has been significant attention paid to areas of "the return to sport, re-repture rate and functional recovery after anterior cruciate ligament reconstruction" in this specific population. These aspects have emerged as key directions for future research in this field.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-ß1/Smad3 Signaling Pathway.

OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells†.

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers, and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals. Summary Sentence  The present study investigated the effect of NGF on testosterone synthesis in porcine theca cells. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells.

Exosomal long non-coding RNA AU020206 alleviates macrophage pyroptosis in atherosclerosis by suppressing CEBPB-mediated NLRP3 transcription.

Recent studies have suggested exosomes (EXO) as potential therapeutic tools for cardiovascular diseases, including atherosclerosis (AS). This study investigates the function of bone marrow stem cell (BMSC)-derived exosomes (EXO) on macrophage pyroptosis in AS and explores the associated mechanism. BMSC-EXO were isolated from healthy mice and identified. RAW264.7 cells (mouse macrophages) were exposed to oxLDL to simulate an AS condition. BMSC-EXO treatment enhanced viability and reduced lactate dehydrogenase release of macrophages. An animal model of AS was established using ApoE-/- mice. BMSC-EXO treatment suppressed plaque formation as well as macrophage and lipid infiltration in mouse aortic tissues. Moreover, BMSC-EXO decreased concentrations of pyroptosis-related markers interleukin (IL)-1ß, IL-18, cleaved-caspase-1 and gasdermin D in vitro and in vivo. Long non-coding RNA AU020206 was carried by the BMSC-EXO, and it bound to CCAAT enhancer binding protein beta (CEBPB) to block CEBPB-mediated transcriptional activation of NLR family pyrin domain containing 3 (NLRP3). Functional assays revealed that silencing of AU020206 aggravated macrophage pyroptosis and exacerbated AS symptoms in mice. These exacerbations were blocked upon CEBPB silencing but then restored after NLRP3 overexpression. In conclusion, this study demonstrates that AU020206 delivered by BMSC-EXO alleviates macrophage pyroptosis in AS by blocking CEBPB-mediated transcriptional activation of NLRP3.

TL1A promotes metastasis and EMT process of colorectal cancer.

Background: Metastasis is the major problem of colorectal cancer (CRC) and is correlated with the high mortality. Tumor necrosis factor-like cytokine 1A (TL1A) is a novel regulatory factor for inflammatory diseases. This work aimed to investigate the role of TL1A in CRC metastasis. Method: AOM/DSS-induced mouse model, xenograft tumor model and metastasis murine model were established to mimic the colitis-associated CRC and investigate CRC growth and metastasis in vivo. Colon tissues were assessed by hematoxylin/eosin (HE) staining and immunohistochemistry (IHC). CRC cell metastasis in vivo was observed using in vivo imaging system (IVIS). Cell viability and proliferation were examined using cell counting kit 8 (CCK-8) and EdU experiments. The expression of tumor growth factor ß (TGFß) and metastatic biomarkers were detected using western blotting experiment. The in vitro cell metastasis was measured by Transwell. Results: Knockdown of TL1A notably suppressed the generation of colonic tumors in azoxymethane/dextran sodium sulfate (AOM/DSS) model, suppressed in vivo CRC cell growth, as well as lung and liver metastasis. The inflammation response and inflammatory cell infiltration in tumor sites were decreased by TL1A depletion. The in vitro CRC cell growth and metastasis was also suppressed by shTL1A, along with altered expression of epithelial mesenchymal transition (EMT) biomarkers. TL1A depletion suppressed the level of the TGF-ß1 receptor (TßRI) and phosphorylation of Smad3 in CRC cells. Stimulation with TGF-ß recovered the CRC cell migration and invasion that suppressed by shTL1A. Conclusion: Our work implicated TL1A as a promoter of CRC generation and metastasis and defines TGF-ß/Smad3 signaling as mediator of TL1A-regualated CRC cell metastasis.

Follicular fluid exosomes inhibit expression of BTG2 and promote glucose uptake in granulosa cells by delivering miR-21-5p.

Glucose metabolism in granulosa cells (GCs) is essential for follicle development and oocyte maturation. Porcine follicular fluid exosomes promote the proliferation of porcine GCs and the synthesis of steroid hormones. However, their role in regulating glucose uptake in GCs is unclear. The objective of this study was to elucidate the effects of porcine follicular fluid exosomes on glucose uptake in porcine GCs and the intrinsic mechanisms involved. First, transcriptome sequencing revealed that glucose metabolism-related pathways were altered in GCs treated with follicular fluid exosomes. Next, in vitro culture experiments showed that glucose uptake was increased and the IRS1/AKT signaling pathway was activated in GCs after treatment with follicular fluid exosomes. Finally, miRNA sequencing of follicular fluid exosomes revealed that miR-21-5p was the most abundant miRNA. Subsequent investigations indicated that miR-21-5p promoted glucose uptake in GCs by targeting BTG2, which activated the IRS1/AKT signaling pathway. In conclusion, the findings of this study indicate that porcine follicular fluid exosomes promote glucose uptake in porcine GCs by delivering miR-21-5p, which inhibits the expression of BTG2, activating the IRS1/AKT signaling pathway.

lnc RNA LOC102163816 Promotes Proliferation of Porcine Follicular Granulosa Cells Via miR-455-3p/PTK2B/PI3K/AKT Pathway.

The proliferation and differentiation of granulosa cells (GCs) is a crucial process in follicular development. However, the molecular regulatory mechanism of follicular proliferation and differentiation of GCs needs further research. Studies have reported that follicular fluid exosomes are involved in regulation of proliferation of GCs, but the specific mechanism is unclear. This study demonstrated that LOC102163816 is upregulated in porcine GCs treated with follicular fluid exosomes. Further study defined LOC102163816 to be a novel long noncoding RNA that is highly homologous to human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and enriched in porcine follicular fluid exosomes. We have speculated that LOC102163816 might have a cell-proliferative effect similar to that of MALAT1. We found that overexpression of LOC102163816 promoted transition from the G1 phase to the S phase of the cell cycle, thereby promoting proliferation of GCs. To explore the specific mechanism underlying this promotion of proliferation, miRNA sequencing was performed after overexpression of LOC102163816. Our results showed that LOC102163816 sponged miR-455-3p, promoting expression of protein tyrosine kinase 2 beta (PTK2B), thereby activating the PI3K/AKT signaling pathway to regulate proliferation of porcine follicular GCs. These findings provide useful insights into follicular development.

CCN6 improves hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: CCN6 is a secretory protein with functions of maintaining mitochondrial homeostasis and anti-oxidative stress; and yet, whether it is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH) is still obscure. We investigated the role and mechanism of CCN6 in the development of NASH. METHODS: Human liver tissue samples were collected to detect the expression profile of CCN6. High-fat-high-cholesterol (HFHC) and methionine choline-deficient (MCD) diet were applied to mice to establish NASH animal models. Liver-specific overexpression of CCN6 was induced in mice by tail vein injection of adeno-associated virus (AAV), and then the effect of CCN6 on the course of NASH was observed. Free fatty acid (FFA) was applied to HepG2 cells to construct the cell model of steatosis, and the effect of CCN6 was investigated by knocking down the expression of CCN6 through small interfering RNA (siRNA) transfection. RESULTS: We found that CCN6 expression was significantly downregulated in the liver of NASH. We confirmed that liver-specific overexpression of CCN6 significantly attenuated hepatic steatosis, inflammation response and fibrosis in NASH mice. Based on RNA-seq analysis, we revealed that CCN6 significantly affected the MAPK pathway. Then, by interfering with apoptosis signal-regulating kinase 1 (ASK1), we identified the ASK1/MAPK pathway pairs as the targets of CCN6 action. CONCLUSIONS: CCN6 protects against hepatic steatosis, inflammation response and fibrosis by inhibiting the activation of ASK1 along with its downstream MAPK signalling. CCN6 may be a potential therapeutic target for the treatment of NASH.

Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate experimental non-alcoholic steatohepatitis via Nrf2/NQO-1 pathway.

BACKGROUND: No approved effective therapy for non-alcoholic steatohepatitis (NASH) is currently available. Exosomes derived from mesenchymal stem cells (MSCs) perform the functions such as inhibiting inflammation, anti-oxidative stress, regulating immunity, but it is not clear whether human umbilical cord mesenchymal stem cells (hUC-MSCs) exosomes protect against NASH through Nrf2/NQO-1 pathway. Therefore, this study was conducted to investigate the effects of hUC-MSCs exosomes on NASH through Nrf2/NQO-1 pathway in vivo and in vitro. METHODS: C57BL/6J male mice were fed with high fat and high cholesterol diet (HFHC) and methionine choline deficiency diet (MCD). Mice were treated with or without hUC-MSCs exosomes by tail intravenous injection. The liver histology, lipid metabolism and oxidative stress were evaluated. HepG2 and AML12 cells were incubated with palmitic acid (PA) and MCD conditioned medium, respectively. Then the therapeutic effect of hUC-MSCs exosomes in steatotic cells was evaluated. To elucidate the signaling pathways, the Nrf2-specific blocker ML385 was applied to intervene in vitro. RESULTS: In NASH models, hUC-MSCs exosomes attenuated steatosis in hepatocytes, altered the abnormal expression of lipid-related genes including SREBP-1c, PPAR-α, Fabp5, CPT1α, ACOX and FAS, suppressed the hepatic inflammatory responses by decreasing the expression of F4/80+ macrophages, CD11c+ macrophages as well as the content of TNF-α and IL-6. hUC-MSCs exosomes also inhibited oxidative stress by reducing the level of MDA, CYP2E1 and ROS, increasing the activity of SOD and GSH in hepatocytes. Notably, hUC-MSCs exosomes enhanced the protein ratio of p-Nrf2/Nrf2 and the protein expression of NQO-1. Moreover, in vitro, the therapeutic effects of hUC-MSCs exosomes on lipid deposition and ROS were reversed by ML385. Also, ML385 reduced the protein expression of p-Nrf2 and NQO-1 in vitro. CONCLUSION: Nrf2/NQO-1 antioxidant signaling pathway may play a key role in the treatment of NASH by hUC-MSCs exosomes.

miRNA-320 inhibits colitis-associated colorectal cancer by regulating the IL-6R/STAT3 pathway in mice.

Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice. Methods: CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR. Results: miRNA-320 was downregulated in CAC mice (0.57±0.13 vs. 1.00±0.12, t=-5.95, P<0.001). miRNA-320 decreased the disease activity index (DAI) scores, improved colonic inflammation, and inhibited tumor formation (tumor number: 8.00±2.90 vs. 13.67±2.73, t=-3.49, P<0.01) in mice with CAC. miRNA-320 suppressed the expression of BCL-xl, PCNA, and Ki-67 (0.38±0.07 vs. 0.69±0.08, t=-7.30, P<0.001). miRNA-320 inhibited colon cancer cell proliferation, migration, and invasion. miRNA-320 significantly inhibited the levels of IL-6R [colon tissue messenger RNA (mRNA): 4.06±1.44 vs. 10.05±1.55, t=-6.94, P<0.001], STAT3, and p-STAT3 in vivo and in vitro. Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320. Conclusions: miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.

Regulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma.

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre-miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl-prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55ß subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55ß-containing PP2A in miRNA expression and may shed light on HCC pathogenesis.

Exosomes Derived from Mesenchymal Stem Cells Ameliorate the Progression of Atherosclerosis in ApoE-/- Mice via FENDRR.

Exosomes (EXO) are extracellular vesicles with lipid bilayer membrane structure containing noncoding RNA, DNA, and other molecules which mediate biological functions. The importance of EXO derived from mesenchymal stem cells (MSCs) has been underlined in cardiovascular diseases. However, the functional role of long non-coding RNA (lncRNA) released by MSCs-EXO on atherosclerosis (AS) was unknown. We aimed to investigate the effects of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) released from MSC-derived EXO on AS. The accumulation of oxidized low-density lipoprotein (oxLDL) caused AS in mice and damage to human vascular endothelial cells (HUV-EC-C). MSC-EXO restored HUV-EC-C activity and alleviated arterial injury. LncRNA microarrays revealed that FENDRR was delivered to cells and tissues by MSC-EXO. FENDRR bound to microRNA (miR)-28 to regulate TEA domain transcription factor 1 (TEAD1) expression. Moreover, FENDRR knockdown exacerbated cell injury and arterial injury in mice. miR-28 inhibitor reversed the effects of FENDRR silencing and reduced atherosclerotic plaque formation. While loss of TEAD1 mitigated the effect of miR-28 inhibitor and accentuated HUV-EC-C injury in vitro and AS symptoms in vivo. Our results demonstrated that MSC-EXO secreted FENDRR to treat AS. FENDRR competed with TEAD1 to bind to miR-28, thereby reducing HUV-EC-C injury and atherosclerotic plaque formation.

Traditional Chinese Medicine in Cancer Care: An Overview of 5834 Randomized Controlled Trials Published in Chinese.

BACKGROUND: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care. METHODS: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study. RESULTS: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment. CONCLUSION: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.

A novel therapeutic approach for inflammatory bowel disease by exosomes derived from human umbilical cord mesenchymal stem cells to repair intestinal barrier via TSG-6.

BACKGROUND: Exosomes as the main therapeutic vectors of mesenchymal stem cells (MSC) for inflammatory bowel disease (IBD) treatment and its mechanism remain unexplored. Tumor necrosis factor-α stimulated gene 6 (TSG-6) is a glycoprotein secreted by MSC with the capacities of tissue repair and immune regulation. This study aimed to explore whether TSG-6 is a potential molecular target of exosomes derived from MSCs (MSCs-Exo) exerting its therapeutic effect against colon inflammation and repairing mucosal tissue. METHODS: Two separate dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD mouse models were intraperitoneally administered MSCs-Exo extracted from human umbilical cord MSC (hUC-MSC) culture supernatant. Effects of MSCs-Exo on intestinal inflammation, colon barrier function, and proportion of T cells were investigated. We explored the effects of MSCs-Exo on the intestinal barrier and immune response with TSG-6 knockdown. Moreover, recombinant human TSG-6 (rhTSG-6) was administered exogenously and colon inflammation severity in mice was evaluated. RESULTS: Intraperitoneal injection of MSCs-Exo significantly ameliorated IBD symptoms and reduced mortality rate. The protective effect of MSCs-Exo on intestinal barrier was demonstrated evidenced by the loss of goblet cells and intestinal mucosa permeability, thereby improving the destruction of tight junctions (TJ) structures and microvilli, as well as increasing the expression of TJ proteins. Microarray analysis revealed that MSCs-Exo administration downregulated the level of pro-inflammatory cytokines and upregulated the anti-inflammatory cytokine in colon tissue. MSCs-Exo also modulated the response of Th2 and Th17 cells in the mesenteric lymph nodes (MLN). Reversely, knockdown of TSG-6 abrogated the therapeutic effect of MSCs-Exo on mucosal barrier maintenance and immune regulation, whereas rhTSG-6 administration showed similar efficacy to that of MSCs-Exo. CONCLUSIONS: Our findings suggested that MSCs-Exo protected against IBD through restoring mucosal barrier repair and intestinal immune homeostasis via TSG-6 in mice.

2-Methyl Nonyl Ketone From Houttuynia Cordata Thunb Alleviates LPS-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells.

Mastitis is one of the most common diseases in dairy cows, causing huge economic losses to the dairy industry every year. Houttuynia Cordata Thunb ( H.cordata ) is a traditional Chinese herbal medicine that is widely used in clinical treatment. However, the therapeutic effect of 2-methyl nonyl ketone (MNK), the main volatile oil component in the aqueous vapor extract of H. cordata, on mastitis has been less studied. The purpose of this study was to investigate the protective effect and mechanism of MNK against lipopolysaccharide (LPS)-induced mastitis in vitro. The results showed that MNK pretreatment of the bovine mammary epithelial cell line (MAC-T) enhanced cell viability and inhibited LPS-induced reactive oxygen species (ROS) production and inflammatory response. MNK reduced the production of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor-α (TNF-α) by repressing LPS-induced activation of Toll-like receptor 4-nuclear factor-κB (TLR4-NF-κB) signaling pathway. In addition, MNK protected cells from inflammatory responses by blocking the downstream signaling of inflammatory factors. MNK also induced Heme Oxygenase-1 ( HO-1 ) production by Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through AKT and extracellular signal-regulated kinase (ERK) pathways, thereby reducing LPS-induced oxidative damage for MAC-T cells. In conclusion, MNK played a protective role against LPS-induced cell injury. This provides a theoretical basis for the research and development of MNK as a novel therapeutic agent for mastitis.

TNF-Like Ligand 1 Aberrance Aggravates Nonalcoholic Steatohepatitis via M1 Macrophage Polarization.

Nonalcoholic steatohepatitis (NASH) is a progressive, chronic liver disease worldwide which imposes a large economic burden on society. M1/M2 macrophage balance destruction and recruitment of mononuclear immune cells to the liver play critical roles in NASH. Several studies have shown that the expression of TNF-like ligand 1 aberrance (TL1A) increased in macrophages associated with many inflammatory diseases, for example, inflammatory bowel disease, primary biliary cholangitis, and liver fibrosis. One recent research showed that weight, abdominal adipose, and liver leptin, one of the critical fat cytokines, were reduced in TL1A knockout mice. However, the functional and molecular regulatory mechanisms of TL1A on macrophage polarization and recruitment in NASH have yet to be clarified. The authors found that high fructose high fat diet and methionine-choline deficiency diet induced the expression of TL1A in macrophages of liver tissue from murine NASH models. Myeloid-specific TL1A overexpressed mice showed exacerbated steatohepatitis with increased hepatic lipid accumulation, inflammation, liver injury, and apoptosis. M1 macrophages' infiltration and the production of proinflammatory and chemotactic cytokines increased in liver of NASH mouse models with myeloid-specific TL1A overexpressed. Furthermore, this paper revealed that bone marrow-derived macrophages and Kupffer cells with overexpression of TL1A exacerbated the lipid accumulation and expression of proinflammatory factors in the murine primary hepatocytes after free fatty acid treatment in vitro. In conclusion, TL1A-mediated M1-type macrophage polarization and recruitment into the liver promoted steatohepatitis in murine NASH.

A Survey on HIV/AIDS-Related Knowledge, Attitudes, Risk Behaviors, and Characteristics of Men Who Have Sex with Men among University Students in Guangxi, China.

In recent years, the prevalence of human immunodeficiency virus (HIV) infection among Chinese university students has increased significantly, and HIV transmission among men who have sex with men (MSM) comprises more than half of the new cases. There is still a lack of research investigating the incidence of male-to-male sex, the attitudes towards MSM, and the awareness of HIV/AIDS among university students in Guangxi, one of the HIV high-risk areas in China. Therefore, we performed a cross-sectional investigation among 578 male students, recruited by stratified sampling, in universities in Nanning, Guangxi, between January 2016 and March 2017. Researcher-administered anonymous questionnaires were completed. Self-recognition as MSM was found in 8.48% of the subjects. Compared with non-MSM, university student MSM included more people over the age of 20 (OR = 4.95), had less migration from other districts of Guangxi (OR = 0.26), and the majority were nonmedical students (OR = 8.99). In total, 63.25% of the male student participants reported a lack of acceptance of MSM, while 35.47% acknowledged barriers between themselves and acquaintances who were MSM. Overall, 67.30% of the subjects correctly answered questions related to AIDS knowledge. The proportion of MSM subjects who answered the AIDS-related questions completely correctly was significantly lower than that of non-MSM subjects (42.86% vs. 69. 57%, respectively, OR: 0.33), but the self-recognition risk of MSM was significantly higher than that of non-MSM (OR = 2.59). Risky behaviors associated with HIV infections, including smoking, alcohol consumption, drug abuse, and inconsistent condom use, were significantly higher among the MSM participants. The percentages of student's willingness to accept MC and PrEP were 70.93% and 77.51%, respectively. These results raise the alarm that university student MSM in Guangxi, China, require urgent public attention and more effective health education, including the education on MC and PrEP.

Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression.

OBJECTIVES: To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis. METHODS: Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4+ T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry. RESULTS: DSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-ß+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-ß+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-ß+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-ß+IL-4 group. CONCLUSIONS: TL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.

A smartphone-based platform for point-of-use determination of alkaline phosphatase as an indicator of water eutrophication.

A smartphone-based detection platform for the determination of alkaline phosphatase (ALP) is described. The method is based on the rational design of the stimulus-response of 7-methoxycoumarin-3-carboxylic acid (7-MC-3-COOH)-functionalized Eu-AMP infinite coordination polymer (ICP) nanoparticles. The blue fluorescence of 7-MC-3-COOH at 403 nm was suppressed, while the red fluorescence of Eu3+ at 615 nm was sensitized after the formation of 7-MC-3-COOH@Eu-AMP ICP. Upon exposure to ALP, the dephosphorylation of AMP resulted in the destruction of 7-MC-3-COOH@Eu-AMP ICP, and thereby, the blue fluorescence of 7-MC-3-COOH recovered; in the meantime, the sensitized red fluorescence was quenched. With the fluorescence intensity ratio F615/F430 as the signal readout, ALP can be detected within a concentration range 0.001 to 0.15 U mL-1, and the limit of detection (LOD) was 0.00035 U mL-1. Moreover, fluorescence color changes from red to blue could also be recognized by a portable device with the smartphone as a signal reader, and direct point-of-use testing (POUT) for ALP within a concentration range 0.005 to 0.7 U mL-1 could be realized, with LOD of 0.0015 U mL-1. Endowed with high sensitivity and superior reliability, the assay enabled direct monitoring of P-related water eutrophication in a freshwater lake with ALP as an indicator. Graphical abstract A smartphone-based platform for point-of-use determination of alkaline phosphatase.

TL1A modulates the severity of colitis by promoting Th9 differentiation and IL-9 secretion.

AIMS: TL1A was reported to contribute to the susceptibility to ulcerative colitis (UC). However, the molecular mechanisms of TL1A in UC development are poorly understood. We aimed to investigate the role of TL1A in colitis, and reveal the regulatory mechanism of TL1A in chronic colitis development. MAIN METHODS: Wild-type mice and transgenic mice with overexpressing TL1A in lymphocytes were used to construct chronic DSS colitis models. To investigate the molecular mechanism in vitro, CD4+ T cells were sorted from spleens and mesenteric lymph node cells to induce Th9 cells. Biopsy specimens from ulcerative colitis patients were collected for in vivo validation. KEY FINDINGS: The elevated TL1A expression in chronic DSS colitis models exacerbated intestinal inflammation. The differentiation of Th9 cells, IL-9 secretion and production of TGF-ß, IL-4 and PU.1 was significantly enhanced in transgenic mice with TL1A overexpression. In vitro results showed that TL1A enhanced the Th9 cells, IL-9 and PU.1 production, while TL1A antibodies inhibited their production. In human translational studies, patients with ulcerative colitis with elevated TL1A expression also exhibited more serious inflammation with higher levels of Th9 cells, IL-9 and PU.1 expression. SIGNIFICANCE: We presented a possible mechanism of TL1A in UC development that TL1A may promote the differentiation of Th9 cells and enhanced IL-9 secretion by up-regulating the expression of TGF-ß, IL-4 and PU.1, which provided a novel perspective to study the UC pathogenesis, and indicated that targeting of TL1A signal pathway may by a likely strategy for the treatment of chronic colitis.