Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer. METHODS: The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis. RESULTS: Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%). CONCLUSION: In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.

Probing the Alcoholysis Degree of Polyvinyl Alcohol by Synergistic Coordination-Regulated Fluorescence.

Polyvinyl alcohol (PVA) with abundant hydroxyl groups (-OH) has been widely used for membranes, hydrogels, and films, and its function is largely affected by the alcoholysis degree. Therefore, the development of rapid and accurate methods for alcoholysis degree determination in PVAs is important. In this contribution, we have proposed a novel fluorescence-based platform for probing the alcoholysis degree of PVA by using the (E)-N-(4-methoxyphenyl)-1-(quinolin-2-yl)methanimine (QPM)-Zn2+ complex as the reporter. The mechanism study disclosed that the strong coordination between -OH and Zn2+ induced the capture of the QPM-Zn2+ complex and promoted its subsequent immobilization into the noncrystalline area. The immobilization of the QPM-Zn2+ complex restricted its molecular rotation and reduced the nonirradiative transition, thus yielding bright emissions. In addition, the practical applications of this proposed method were further validated by the accurate alcoholysis degree determination of blind PVA samples with the confirmation of the National Standard protocol. It is expected that the developed fluorescence approach in this work might become an admissive strategy for screening the alcoholysis degree of PVA.

Genetics of High-Altitude Pulmonary Edema.

High-altitude pulmonary edema (HAPE) is the main cause of nontraumatic death at high altitude. HAPE development is not only related to the mode and speed of ascent and the maximum altitude reached, but also individual susceptibility plays an important role. In susceptible individuals, hypoxic pulmonary vasoconstriction leads to exaggerated elevated pulmonary arterial pressures and capillary leakage in the lungs. Thus, this review provides an overview of studies investigating the genetic background in HAPE susceptibles by focusing on specific variants, entire genes, genome-wide signatures, or family studies.

Reduced surface accumulation of swimming bacteria in viscoelastic polymer fluids.

Surface-associated bacterial communities flourish in nature and in the body of animal hosts with abundant macromolecular polymers. It is unclear how the endowed viscoelasticity of polymeric fluids influences bacterial motile behavior in such environments. Here, we combined experiment and theory to study near-surface swimming of flagellated bacteria in viscoelastic polymer fluids. In contrast to the swimming behavior in Newtonian fluids, we discovered that cells swim in less curved trajectories and display reduced near-surface accumulation. Using a theoretical analysis of the non-Newtonian hydrodynamic forces, we demonstrated the existence of a generic lift force acting on a rotating filament near a rigid surface, which arises from the elastic tension generated along curved flow streamlines. This viscoelastic lift force weakens the hydrodynamic interaction between flagellated swimmers and solid surfaces and contributes to a decrease in surface accumulation. Our findings reveal previously unrecognized facets of bacterial transport and surface exploration in polymer-rich environments that are pertinent to diverse microbial processes and may inform the design of artificial microswimmers capable of navigating through complex geometries.

Clinicopathological features, prognostic significance, and associated tumor cell functions of family with sequence similarity 111 member B in pancreatic adenocarcinoma.

BACKGROUD: Among digestive tract tumors, pancreatic adenocarcinoma (PAAD) has a high degree of malignancy. Therefore, it is important to search for pancreatic adenocarcinoma-related differential genes and new oncogene therapeutic targets for early diagnosis, treatment, and prognosis of pancreatic adenocarcinoma. AIMS: This study aims to investigate the expression and clinical significance of Family with sequence similarity 111 member B (FAM111B) in PAAD. MATERIALS & METHODS: Bioinformatics was used to analyze the relationship between FAM111B expression and pancreatic adenocarcinoma and to predict its role in related pathways. Tissue microarrays were used to assess the levels of FAM111B in pancreatic cancer tissues by immunohistochemical staining, and the effects of FAM111B expression levels on apoptosis, proliferation, invasion and migration of tumor cells were observed and verified by in vitro cellular assays. RESULTS: FAM111B expression was higher in PAAD tissue than in matched normal tissues (p < 0.05). The expression level of FAM111B, the metastatic status of lymph nodes was an independent prognostic factor for PAAD survival (p < 0.05). Meanwhile, overexpression of FAM111B promoted PAAD cell proliferation, migration, invasion and inhibited PAAD cell apoptosis (p < 0.05). In contrast, knockdown of FAM111B triggered the opposite result (p < 0.05). In the results of GSEA, it was shown that FAM111B may be involved in PAAD progression through p53 signaling pathway, cell cycle, and other signaling pathways (p < 0.05 and FDR q-val <0.25). FAM111B is highly expressed in PAAD tissues and is closely associated with poor prognosis of PAAD. CONCLUSION: FAM111B significantly promotes the proliferation, invasion, and migration of pancreatic adenocarcinoma cells while it inhibits their apoptosis. FAM111B may be a new biomarker for PAAD. It may provide a new direction for the treatment and diagnosis of PAAD.

Identification of Gene Coexpression Modules and Prognostic Genes Associated with Papillary Thyroid Cancer.

Thyroid cancer is a great part of the endocrine tumor with an increasing incidence. Papillary thyroid carcinoma (PTC) is the most common subtype. With the enormous pace taken in the microarray technology, bioinformatics is applied in data mining more frequently. Weighted gene coexpression network analysis (WGCNA) can perform analysis combining clinic information. We performed WGCNA for prognostic genes associated with PTC. From the GEO profile, we got ten modules. We identified a key module that was closest to patients' survival time. Then, we screened five hub genes (ATRX, BOD1L1, CEP290, DCAF16, and NEK1) from the key module based on the clinical information from TCGA. These five genes not only significantly differ between the normal and tumor groups but have prognostic value. The receiver operating characteristic (ROC) curve indicated that they had the potential to serve as prognostic genes. We performed next-generation sequencing using the PTC tissue to get more convincing evidence. Besides, we established a new signature and verified it through K-M plots and ROC. The signature could be an independent factor for the prognosis of PTC, and we built a nomogram to carry out a quantitative study. In a word, the hub genes we explored in the study deserved more basic and clinical research.

Visualization of Polymer-Surfactant Interaction by Dual-Emissive Gold Nanocluster Labeling.

Polymer-surfactant interaction decides the performance of corresponding complexes, making its rapid and intuitionistic visualization important for enhancing the performance of products and/or processing in related fields. In this study, the fluorescence visualization of the interaction between cationic hyperbranched polyethyleneimine and anionic sodium dodecyl sulfonate surfactant was realized by dual-emissive gold nanocluster labeling. The sensing mechanism was due to the interaction-induced polymer conformation change, which regulated the molecular structure and subsequent photoradiation process of the gold nanoclusters. All three inflection points of the interactions between the polymers and the surfactants were obtained by the change in fluorescence emission ratio of the designed dual-emissive gold nanoclusters. Moreover, these inflection points are verified by the hydrodynamic diameter and zeta potential measurements.

Transcriptome Analysis Reveals Molecular Underpinnings of Common Carp (Cyprinus carpio) Under Hypoxia Stress.

As an essential environmental factor that affects the economic benefits of aquaculture, hypoxia is one of the urgent problems to be solved in the aquaculture fish breeding industry. Common carp (Cyprinus carpio) is a critical economic fish in China, and at present, there are many breeding strains of common carp with different character advantages in China, including Hebao red carp (C. carpio var wuyuanesis) and Songpu mirror carp (C. carpio var specularis). Even if the environmental adaptation of common carp is generally strong, the genetic background of hypoxia tolerance in different strains of common carp is unclear yet. This study tested the hypoxia tolerance of Songpu minor carp, Hebao red carp, and their hybrid F1 population by an acute hypoxia treatment. Muscle and liver tissues were used for transcriptome sequencing analysis to identify the key factors for hypoxia tolerance and explore the potential genetic mechanism for breeding high hypoxia tolerance in common carp. The comparative transcriptomic analysis revealed abundant hypoxia response-related genes and their differential regulation mechanism in these two tissues of different common carp strains under acute hypoxia, including immune response, cellular stress response, HIFs (hypoxia-inducible factors), MAP kinase, iron ion binding, and heme binding. Our findings will facilitate future investigation on the hypoxia response mechanism and provide a solid theoretical basis for breeding projects in common carp.

Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension.

BACKGROUND: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years. METHODS: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes' discovery. RESULTS: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH. CONCLUSIONS: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes.

High platelet count predicts poor prognosis in HCC patients undergoing TACE: a propensity score-matched analysis.

BACKGROUND: The aim of this study was to retrospectively evaluate the prognostic value of the pretreatment platelet (PLT) count in patients with hepatitis B virus (HBV)-related intermediate-advanced hepatocellular carcinoma (HCC) complicated with cirrhosis undergoing transcatheter arterial chemoembolization (TACE). RESEARCH DESIGN AND METHODS: We assessed 362 patients with HBV-related intermediate-advanced HCC complicated with cirrhosis undergoing TACE. Patients were divided into low (≤96 × 109/L) and high (>96 × 109/L) PLT groups. Propensity score matching (PSM) was performed to eliminate the imbalance in potential confounding factors. The endpoint was time to progression (TTP). RESULTS: After PSM, the high and low PLT groups had 97 patients each. The TTP was significantly longer in the low PLT group than in the high PLT group (log-rank test, p < 0.001). A high pretreatment PLT count was an independent predictor of poor tumor response (OR 4.724; 95% CI 1.889-11.815; P = 0.001) and short TTP (HR = 3.598; 95% CI: 2.570-5.036; P < 0.001). Subgroup analysis showed that a high PLT count increased the risk of progression across almost all subgroups. CONCLUSIONS: The pretreatment PLT count has potential value in predicting the prognosis of patients with intermediate-advanced HCC undergoing TACE.

Unravelling the role of surface modification in the dermocompatibility of silver nanoparticles in vitro and in vivo.

A clearer picture of interactions between differently coated silver nanoparticles (AgNPs) and biological interfaces that are confronted with by the dermal exposure route is of utmost importance for the risk assessment of various AgNPs-based formulations utilized in the medical and dermocosmetic fields. This work sought to understand how surface modification of AgNPs, especially those produced by green synthesis strategy, affects the surface chemistry and dermocompatibility. Phytosynthetized AgNPs diverse in bio-reducing/capping agents i.e. chlorogenic acid, glycyrrhizic acid and gallic acid, were prepared by a bioinspired green approach and characterized in terms of size, shape, crystal phase, surface charge, structure and antioxidant activity. Chemically synthetized AgNPs stabilized by trisodium citrate or polyvinylpyrrolidone were also analyzed for comparison. The biological test results illustrate that varying coating material for AgNP stabilization results in differential toxicity against dermal microbes and HaCaT keratinocytes in vitro and affects dermal absorption through intact/compromised skin in vivo. Among all test samples, the citrate-stabilized AgNPs displayed the maximum cytotoxicity and dermal absorption. It is also of interest to note that the phytosynthetized AgNPs with chlorogenic acid exhibited superior antioxidant activity, attenuated cytotoxicity and minimal skin deposition, while those modified with glycyrrhizic acid demonstrated a preferentially antibacterial activity against the pathogenic (Escherichia coli and Staphylococcus aureus) over the beneficial strains (Staphylococcus epidermidis) inhabiting human skin. Furthermore, percutaneous absorption of AgNPs into live epidermis was observed on all 7-13 nm sized AgNPs, irrespective of surface coating, with more pronounced skin deposition of silver species occurring for the chemically-synthetized AgNPs within compromised skin. Given all these results, it is concluded that surface modification with particular phytochemicals may render AgNPs with enhanced dermocompatibility or antimicrobial activity. This study provides a basis for risk assessments of phytosynthetized AgNPs in consumer products and suggests the possibility of tailoring AgNPs applicability via green chemistry approach.

YBX has functional roles in CpG-ODN against cold stress and bacterial infection of Misgurnus anguillicaudatus.

Misgurnus anguillicaudatus (M. anguillicaudatus) is a widely cultivated fish. However, in M. anguillicaudatus breeding, the frequent cold stress during daily breeding could induce immune suppression and increase the risk of infection, causing serious economic loss. Based on existing findings, CpG Oligonucleotides (CpG-ODNs) may be an ideal protective agent for low temperature fish breeding, performing anti-infective when faced with cold stress with cold shock proteins Y box binding proteins (YBX). Although YBX has pleiotropic functions, its roles in CpG-ODNs-mediated immunity (especially under cold situations) remain largely unexplored. To clarify the relationship among them, we identified the YBX1/YBX2 in M. anguillicaudatus and analyzed using a series of bioinformatics methods. After that, we immunized the fish with 3 types of CpG-ODNs and challenged with Aeromonas hydrophila (A. hydrophila). Here we showed that the best anti-bacterial effect of CpG-B was accompanied by the significant upregulation of YBX1. And the detection of the YBX1 downstream effectors confirmed that CpG-B induced the YBX1-mediated Th1 oriented responses to A. hydrophila by regulation of the NLRP3 (Caspase-A/-B), IL-1ß, IL-12 and IFN-γ. Afterwards, we found that under cold stress, CpG-B can activate the NLRP3 and NF-κB pathways through YBX1, a key mediator of anti-A. hydrophila in CpG-B immunization. In this study, we demonstrated CpG-B protection against infection in low temperature, and its interaction with YBX1, expanded the research of CpG-ODN under cold stress, and provided a new CpG-ODN application for low temperature fish farming.

Overexpression of pEGF improved the gut protective function of Clostridium butyricum partly through STAT3 signal pathway.

Clostridium butyricum (C. butyricum) is a probiotic that could promote animal growth and protect gut health. So far, current studies mainly keep up with the basic biological functions of C. butyricum, missing the effective strategy to further improve its protective efficiency. A recent report about C. butyricum alleviating intestinal injury through epidermal growth factor receptor (EGFR) inspired us to bridge this gap by porcine epidermal growth factor (EGF) overexpression. Lacking a secretory overexpression system, we constructed the recombinant strains overexpressing pEGF in C. butyricum for the first time and obtained 4 recombinant strains for highly efficient secretion of pEGF (BC/pPD1, BC/pSPP, BC/pGHF, and BC/pDBD). Compared to the wild-type strain, we confirmed that the expression level ranges of the intestinal development-related genes (Claudin-1, GLUT-2, SUC, GLP2R, and EGFR) and anti-inflammation-related gene (IL-10) in IPECs were upregulated under recombinant strain stimulation, and the growth of Staphylococcus aureus and Salmonella typhimurium was significantly inhibited as well. Furthermore, a particular inhibitor (stattic) was used to block STAT3 tyrosine phosphorylation, resulting in the downregulation on antibacterial effect of recombinant strains. This study demonstrated that the secretory overexpression of pEGF in C. butyricum could upregulate the expression level of EGFR, consequently improving the intestinal protective functions of C. butyricum partly following STAT3 signal activation in IPECs and making it a positive loop. These findings on the overexpression strains pointed out a new direction for further development and utilization of C. butyricum. KEY POINTS: • By 12 signal peptide screening in silico, 4 pEGF overexpression strains of C. butyricum/pMTL82151-pEGF for highly efficient secretion of pEGF were generated for the first time. • The secretory overexpression of pEGF promoted the intestinal development, antimicrobial action, and anti-inflammatory function of C. butyricum. • The overexpressed pEGF upregulated the expression level of EGFR and further magnified the gut protective function of recombinant strains which in turn partly depended on STAT3 signal pathway in IPECs.

Pseudomonas aeruginosa outer membrane vesicles ameliorates lung ischemia-reperfusion injury by regulating the balance of regulatory T cells and Th17 cells through Tim-3 and TLR4/NF-κB pathway.

OBJECTIVE: Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of CD4 + T cells with opposite effects which play a crucial role in the pathogenesis of lung injury. In this study, we aim to investigate the protective effect of Pseudomonas aeruginosa outer membrane vesicles (OMVs) preconditioning on lung ischemia-reperfusion (I/R) injury and potential mechanisms. METHODS: Pathogen-free C57BL/6 mice were randomly divided into four groups: control, Control + OMVs, I/R and I/R + OMVs groups. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected and analyzed for pathophysiology and immune mechanism. RESULTS: OMVs not only attenuated tissue injury and respiratory physiologic function but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration. The numbers of total cells, macrophages, neutrophils, and lymphocytes were markedly decreased in the I/R mice following OMVs preconditioning. OMVs also decreased inflammatory cytokines associated with CD4 + T cells in both BALF and serum. In addition, the level of Tregs and its transcription factor forkhead box P3 (Foxp3) were significantly increased, while the level of Th17 cells and its transcription factor retinoid-related orphan receptor γ (RORγt) were significantly decreased following OMVs preconditioning. In the process of exploring the underlying protection mechanisms of OMVs, we found that OMVs preconditioning significantly reduced protein expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation factor 88 (MyD88) and Phosphorylated nuclear factor kappa B (p-NF-κB), but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). CONCLUSIONS: These results suggest that OMVs preconditioning may ameliorate lung I/R injury by regulating the balance of Tregs and Th17 cells through Tim-3 and TLR4/NF-κB pathway.

LINC01133 hampers the development of gastric cancer through increasing somatostatin via binding to microRNA-576-5p.

Aim: Our study aimed at investigating how LINC01133 functions in gastric cancer (GC) progression. Materials & methods: Gain-of-function and loss-of-function approaches were applied to analyze the effects of LINC01133, microRNA-576-5p (miR-576-5p) and somatostatin (SST) on the biological behaviors of GC cells and in tumor-bearing nude mice. Results: GC tissues and cells showed low expression of LINC01133, and LINC01133 overexpression decreased malignant phenotypes of GC cells. Moreover, LINC01133 upregulated SST through binding to miR-576-5p. Overexpressing miR-576-5p or suppressing SST reversed the functions of LINC01133 in biological potentials of GC cells and tumor growth. Conclusion: LINC01133 overexpression may inhibit GC development by downregulation of miR-576-5p and upregulation of SST, which suggests new therapeutic targets for GC.

Intestinal guard: Human CXCL17 modulates protective response against mycotoxins and CXCL17-mimetic peptides development.

Mycotoxin contamination is an ongoing and growing issue that can create health risks and even cause death. Unfortunately, there is currently a lack of specific therapy against mycotoxins with few side effects. On the other hand, the strategic expression of CXCL17 in mucosal tissues suggests that it may be involved in immune response when exposed to mycotoxins, but the exact role of CXCL17 remains largely unknown. Using Caco-2 as a cell model of the intestinal epithelial barrier (the first line of defense against mycotoxins), we showed that a strong production of ROS-dependent CXCL17 was triggered by mycotoxins via p38 and JNK pathways. Under the mycotoxins stress, CXCL17 modulated enhanced immuno-protective response with a remission of inflammation and apoptosis through PI3K/AKT/mTOR. Based on our observed feedback of CXCL17 to the mycotoxins, we developed the CXCL17-mimetic peptides in silico (CX1 and CX2) that possessed the safety and the capability to ameliorate mycotoxins-inducible inflammation and apoptosis. In this study, the identification of detoxifying feature of CXCL17 is a prominent addition to the chemokine field, pointing out a new direction for curing the mycotoxins-caused damage.

SCARF1 promotes M2 polarization of Kupffer cells via calcium-dependent PI3K-AKT-STAT3 signalling to improve liver transplantation.

OBJECTIVES: This study aimed to investigate the protective effect of SCARF1 on acute rejection (AR), phagocytic clearance of Kupffer cells (KCs), M2 polarization and the exact mechanism underlying these processes. METHODS: AAV was transfected into the portal vein of rats, and AR and immune tolerance (IT) models of liver transplantation were established. Liver tissue and blood samples were collected. The level of SCARF1 was detected via WB and immunohistochemical staining. Pathological changes in liver tissue were detected using HE staining. Apoptotic cells were detected using TUNEL staining. KC polarization was assessed via immunohistochemical staining. Primary KCs were isolated and co-cultured with apoptotic T lymphocytes. Phagocytosis of apoptotic cells and polarization of KCs were both detected using immunofluorescence. Calcium concentration was determined using immunofluorescence and a fluorescence microplate reader. The levels of PI3K, p-AKT and P-STAT3 were assessed via WB and immunofluorescence. RESULTS: Compared to the IT group, the level of SCARF1 was significantly decreased in the AR group. Overexpression of SCARF1 in KCs improved AR and liver function markers. Enhanced phagocytosis mediated by SCARF1 is beneficial for improving the apoptotic clearance of AR and promoting M2 polarization of KCs. SCARF1-mediated enhancement of phagocytosis promotes increased calcium concentration in KCs, thus further activating the PI3K-AKT-STAT3 signalling pathway. CONCLUSIONS: SCARF1 promotes the M2 polarization of KCs by promoting phagocytosis through the calcium-dependent PI3K-AKT-STAT3 signalling pathway.

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways.

Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

XBP1s repression regulates Kupffer cell polarization leading to immune suppressive effects protecting liver allograft in rats.

BACKGROUND: Polarized kupffer cells (KCs) influence the immune response after liver transplantation. We report an undiscovered immune regulatory role of X-box binding protein 1 (XBP1) on immune function of kupffer cells (KCs). METHODS: Acute rejection model using rats. RESULTS: We found that suppression of XBP1s in lipopolysaccharide (LPS) -activated KCs could increase the expression of arginase-1 (Arg-1) and CD204 but also decrease the expression levels of MHC-II and CD40 and shift the phenotype markers of KCs toward M2 via the janus kinase (JAK) 3- Signal Transducer And Activator Of Transcription (STAT) 6 pathway, presenting an immunosuppressive function by enhancing anti-inflammatory cytokine secretion and accelerating apoptosis of activated T cells. XBP1s over-expression in KCs shift the phenotype markers on KCs towards M1 via the JAK1-STAT1 pathway and have shown a strong pro-inflammatory property. Down-regulation of XBP1s in KCs changed the phenotype and cytokine secretion profile towards M2 and markedly protected the function and structure of allograft liver, prolonging the recipient's survival compared with control and normal saline groups in rats. CONCLUSIONS: Our findings reveal a novel regulatory mechanism of XBP1 in an induced immuno-suppressive state to protect rat's liver allograft via JAK-STAT mediated KCs polarization.

Diagnostic accuracy of 14-3-3 η protein in rheumatoid arthritis: A meta-analysis.

AIM: To evaluate the overall diagnostic performance of 14-3-3 η protein in patients with rheumatoid arthritis (RA). METHODS: PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published in English before 20 February 2020 were included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of 14-3-3 η protein for RA was conducted by using a random effects model. Subgroup analysis was used to explore the sources of heterogeneity. Deeks' funnel plot asymmetry test was used to evaluate for the presence of publication bias. RESULTS: A total of 13 studies (1554 positive and 1934 negative participants) were included. The pooled sensitivity and specificity were 0.73 (95% CI 0.71-0.75) and 0.88 (95% CI 0.87-0.90), respectively. The pooled positive/negative likelihood were 5.98 (95% CI 4.39-8.14) and 0.28 (95% CI 0.21-0.37), respectively. In addition, the pooled diagnostic odds ratio was 23.48 (95% CI 13.76-40.08) and the area under curve was 0.9245. The results of subgroup analysis indicated that ethnicity and control group might be the source of heterogeneity. The results of sensitivity analysis were stable. No significant publication bias was found. CONCLUSIONS: The current evidence indicated that 14-3-3 η protein has moderate accuracy for the diagnosis of RA.