Diversity and Functionality of Bacteria Associated with Different Tissues of Spider Heteropoda venatoria Revealed through Integration of High-Throughput Sequencing and Culturomics Approaches.

Spiders host a diverse range of bacteria in their guts and other tissues, which have been found to play a significant role in their fitness. This study aimed to investigate the community diversity and functional characteristics of spider-associated bacteria in four tissues of Heteropoda venatoria using HTS of the 16S rRNA gene and culturomics technologies, as well as the functional verification of the isolated strains. The results of HTS showed that the spider-associated bacteria in different tissues belonged to 34 phyla, 72 classes, 170 orders, 277 families, and 458 genera. Bacillus was found to be the most abundant bacteria in the venom gland, silk gland, and ovary, while Stenotrophomonas, Acinetobacter, and Sphingomonas were dominant in the gut microbiota. Based on the amplicon sequencing results, 21 distinct cultivation conditions were developed using culturomics to isolate bacteria from the ovary, gut, venom gland, and silk gland. A total of 119 bacterial strains, representing 4 phyla and 25 genera, with Bacillus and Serratia as the dominant genera, were isolated. Five strains exhibited high efficiency in degrading pesticides in the in vitro experiments. Out of the 119 isolates, 28 exhibited antibacterial activity against at least one of the tested bacterial strains, including the pathogenic bacteria Staphylococcus aureus, Acinetobacter baumanii, and Enterococcus faecalis. The study also identified three strains, GL312, PL211, and PL316, which exhibited significant cytotoxicity against MGC-803. The crude extract from the fermentation broth of strain PL316 was found to effectively induce apoptosis in MGC-803 cells. Overall, this study offers a comprehensive understanding of the bacterial community structure associated with H. venatoria. It also provides valuable insights into discovering novel antitumor natural products for gastric cancer and xenobiotic-degrading bacteria of spiders.

Environmental specificity of karst cave habitats evidenced by diverse symbiotic bacteria in Opiliones.

BACKGROUND: Karst caves serve as natural laboratories, providing organisms with extreme and constant conditions that promote isolation, resulting in a genetic relationship and living environment that is significantly different from those outside the cave. However, research on cave creatures, especially Opiliones, remains scarce, with most studies focused on water, soil, and cave sediments. RESULTS: The structure of symbiotic bacteria in different caves were compared, revealing significant differences. Based on the alpha and beta diversity, symbiotic bacteria abundance and diversity in the cave were similar, but the structure of symbiotic bacteria differed inside and outside the cave. Microorganisms in the cave play an important role in material cycling and energy flow, particularly in the nitrogen cycle. Although microbial diversity varies inside and outside the cave, Opiliones in Beijing caves and Hainan Island exhibited a strong similarity, indicating that the two environments share commonalities. CONCLUSIONS: The karst cave environment possesses high microbial diversity and there are noticeable differences among different caves. Different habitats lead to significant differences in the symbiotic bacteria in Opiliones inside and outside the cave, and cave microorganisms have made efforts to adapt to extreme environments. The similarity in symbiotic bacteria community structure suggests a potential similarity in host environments, providing an explanation for the appearance of Sinonychia martensi in caves in the north.

Therapeutic potential of esculetin in various cancer types (Review).

Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.

Experience in applied veno-arterial extracorporeal membrane oxygenation to support catheter ablation of malignant ventricular tachycardia.

Background: An electrical storm due to malignant ventricular tachycardia (VT) is a life-threatening condition that requires catheter ablation (CA). Most VT arrhythmias evolve over time after acute myocardial infarction, coronary artery bypass grafting, or chronic heart failure. Clinically, only radiofrequency ablation can identify and block all arrhythmia origin points. The procedure necessitates continuous VT induction in patients, resulting in hemodynamic instability; therefore, extracorporeal membrane oxygenation (ECMO) support is required. Earlier studies have reported substantial mortality rates; however, our results are significantly more favorable. In this study, we combined the minimally invasive extracorporeal circulation (MiECC) approach with ECMO to preserve an appropriate ECMO flow rate, thus reducing intraoperative left heart afterload. We report 21 cases illustrating the usefulness of modified veno-arterial (VA)-ECMO in this scenario. Methods: Data of 21 patients supported by the modified VA-ECMO system (MiECC approach combined with the ECMO system) during VT CA in the Wuhan Asia Heart Hospital between June 2020 and July 2021 were reviewed retrospectively. Results: Successful ablation was achieved in 20 out of 21 patients (95%). The median time for ECMO implantation was 206 min. Only two patients experienced complications post-treatment. All patients made complete recovery and were discharged. All patients were alive at the 1-year-follow-up. Conclusions: Our modified VA-ECMO system helped restore systemic circulation in patients experiencing an electrical storm, thus achieving greater electrical stability during VT CA. Pre-insertion of VA-ECMO can achieve even better results.

Factors associated with adaptation level in the older adult residential care facilities: a path analysis.

Background: It has become very common for older adults to relocate to residential care facilities. Yet whether older adults adapt to life in a long-term care residential facility through perception, reflection, and conscious behavioral choices is a challenging social issue. Previous research has shown that adaptation is influenced by physical, mental, psychological, social systems, and other debris factors. However, existing knowledge is often based on unidirectional relationships between these factors and adaptation. Few studies have formally examined bivariate relationships between these factors, and the influence of adaptation between these factors internally remains unclear. Therefore, there is a need to examine the structural causality of adaptation in residential care facilities influenced by a combination of physical, emotional, social and psychological factors, life satisfaction, and social support. Methods: The present cross-sectional study recruited older adults from three residential care facilities in Henan province, China, through convenience sampling. The Chinese Nursing Home Adjustment Scale (NHAS), Geriatric Depression Scale-15 (GDS-15) and Social Support Scale (SSRS), Satisfaction with Life Scale (SWLS), and Barthel Index were employed to measure the older adult' adjustment level, depression level, social support, satisfaction with life, and self-care ability of the BMC, respectively. The relationships between depression, social support, self-care, satisfaction with life, and adaptation were analyzed and a structural equation model was developed. Results: A total of 210 participants completed the questionnaire. The model demonstrated an acceptable fit of the data. The results showed that the difference between life satisfaction and depression on the level of adaptation was 60 and 23%, respectively. Social support and life satisfaction had a positive direct effect on the level of adaptation, both showing a positive correlation with the level of adaptation. Depression, on the other hand, have a direct effect on the level of adaptation and showed a negative correlation with the level of adaptation. Self-care ability indirectly influenced adaptation mediated by social support. Conclusion: Social support has a positive impact on both life satisfaction and depression, which in turn promotes adaptation. As a major source of social support, family members and nursing home staff in residential care facilities can enhance social support for older people through improved interaction, which can have a meaningful and positive impact on levels of adjustment. The model demonstrates the strengthening and weakening of social support, self-care, life satisfaction, and depression levels, which can help inform the development of relevant care health strategies for older people to promote levels of adjustment and improve quality of life.

Three-dimensional printing of cell-laden bioink for blood vessel tissue engineering: influence of process parameters and components on cell viability.

Three-dimensional (3D) bioprinting is a potential therapeutic method for tissue engineering owing to its ability to prepare cell-laden tissue constructs. The properties of bioink are crucial to accurately control the printing structure. Meanwhile, the effect of process parameters on the precise structure is not nonsignificant. We investigated the correlation between process parameters of 3D bioprinting and the structural response of κ-carrageenan-based hydrogels to explore the controllable structure, printing resolution, and cell survival rate. Small-diameter (<6 mm) gel filaments with different structures were printed by varying the shear stress of the extrusion bioprinter to simulate the natural blood vessel structure. The cell viability of the scaffold was evaluated. The in vitro culture of human umbilical vein endothelium cells (HUVECs) on the κ-carrageenan (kc) and composite gels (carrageenan/carbon nanotube and carrageenan/sodium alginate) demonstrated that the cell attachment and proliferation on composite gels were better than those on pure kc. Our results revealed that the carrageenan-based composite bioinks offer better printability, sufficient mechanical stiffness, interconnectivity, and biocompatibility. This process can facilitate precise adjustment of the pore size, porosity, and pore distribution of the hydrogel structure by optimising the printing parameters as well as realise the precise preparation of the internal structure of the 3D hydrogel-based tissue engineering scaffold. Moreover, we obtained perfused tubular filament by 3D printing at optimal process parameters.

Hsa_circ_0046534 accelerates esophageal squamous cell carcinoma proliferation and metastasis via regulating MMP2 expression by sponging miR-339-5p.

Esophageal cancer is one of the most malignant gastrointestinal malignancies. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. In recent years, with developments in basic medicine, it has been demonstrated that the abnormal expression of circular RNA (circRNA) plays an important role in the progression and prognosis of ESCC. This study explored the role and downstream molecular mechanisms of circ_0046534 in ESCC. We identified circ_0046534, which was found to be highly expressed in ESCC tissues and cells. Moreover, the downregulation of circ_0046534 inhibited the proliferation, migration and invasion of ESCC cells and the growth and metastasis of ESCC tumours in vivo. Dual-luciferase reporter assays showed that circ_0046534 sponged miR-339-5p and inhibited the expression of miR-339-5p. Furthermore, MMP2 was identified to be a direct target of miR-339-5p through bioinformatics analysis. In addition, the knockdown of circ_0046534 inhibited the expression of the downstream target gene matrix metalloproteinase 2 (MMP2) by releasing the adsorption of miR-339-5p. Taken together, this study demonstrated that silencing circ_0046534 inhibited the growth and metastasis of ESCC through the miR-339-5p/MMP2 pathway. Circ_0046534 is expected to serve as a new biomarker and target for ESCC and provide a new direction for its diagnosis and treatment.

A qualitative study of the interaction experiences between family caregivers and community nurses for disabled elderly people at home.

BACKGROUND: Family members are currently the main caregivers of the disabled elderly people at home. With declining health and increasing frailty, caregiving of disabled elderly people becomes a task of family caregivers in conjunction with community nurses. Interaction between family caregivers and community nurses can effectively improve the quality of home care for the disabled elderly people. This study aimed to investigate the interaction experiences between family caregivers and community nurses for disabled elderly people at home. METHODS: This research was a study of qualitative descriptions based on semi-structured face-to-face interviews. This study was to purposefully select family caregivers of the disabled elderly and community nurses in Zhengzhou city, Henan Province and explore the interaction patterns between them. Directed content analysis method was used to generate qualitative codes and identify themes. RESULTS: A total of 12 interviews were completed, including 7 family caregivers and 5 community nurses. Four themes were identified: 1) Information interaction; 2) Emotional interaction; 3) Practical interaction; 4) Factors that promote and hinder the interaction. CONCLUSIONS: It was found that the interaction between family caregivers and community nurses was not optimistic. Lack of communication and collaboration between community nurses and caregivers. Providing a new perspective that we can develop and implement intervention to facilitate positive interactions, which will reduce the burden of family caregivers, bring the highest quality of care to older adults with disabilities and improve the quality of care for disabled elderly people. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry on April 19, 2021, number ChiCTR2100045584.

Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Reliability and validity of the Chinese version of the Family Resilience Questionnaire (FaRE Questionnaire) in patients with breast cancer: a cross-sectional study.

OBJECTIVE: The aim of this study was to assess the reliability and validity of the Chinese version of the Family Resilience (FaRE) Questionnaire among patients with breast cancer in China. DESIGN: It was a cross-sectional study, which involved translation, back-translation, cultural adjustment and psychometric testing of a 24-item FaRE Questionnaire. SETTING: Three tertiary hospitals in Zhengzhou, China: respectively are the First Affiliated Hospital of Zhengzhou University, Second Hospital Affiliated to Zhengzhou University and Henan Provincial People's hospital. PARTICIPANTS: A total of 559 patients with breast cancer volunteered to participate in the study PRIMARY OUTCOME MEASURES: Data analysis was performed using the IBM SPSS software V.21.0 and AMOS software V.21.0. Cronbach's α coefficient was used to examine the internal consistency. The test-retest reliability was calculated using the intraclass correlation coefficient on 30 participants. The content validity index was calculated based on the values obtained from six expert opinions. Construct validity test was performed using factor analysis including exploratory factor analysis and confirmatory factor analysis. RESULTS: For the Chinese version of FaRE Questionnaire, the Cronbach's α coefficient of the total questionnaire was 0.909, and Cronbach's α coefficients of four factors were 0.902, 0.932, 0.905 and 0.963, respectively. The test-retest reliability index of the total questionnaire was 0.905. The Scale-Content Validity Index was 0.97, and Item-Content Validity Index ranged from 0.83 to 1.00. The questionnaire included 24 items, exploratory factor analysis extracted four factors with loading >0.4, which could explain 72.146% of the total variance. Confirmatory factor analysis showed the Chinese version of FaRE Questionnaire had an excellent four-factor model consistent with the original questionnaire. CONCLUSION: The Chinese version of FaRE Questionnaire has acceptable reliability and validity among patients with breast cancer in China. It can effectively assess family resilience and provide basis for personalised family resilience interventions for patients with breast cancer.

Cyclopeptide-ß-cyclodextrin/γ-glycerol methoxytrimethoxysilane film for potential vascular tissue engineering scaffolds.

The mortality rate of cardiovascular diseases is the highest among all mortality rates worldwide. Allotransplantation and autotransplantation are limited by rejection reaction and availability. Tissue engineering provides new avenues for the treatment of cardiovascular diseases. However, the current small-diameter (<6 mm) vascular tissue-engineered scaffolds have many challenges, including thrombosis, stenosis, and infection. Small-diameter vascular scaffolds have structural and compositional requirements such as biocompatibility, porosity, and appropriate phase separation. We used liquid-crystal cyclopeptide（CYC）to modify ß-cyclodextrin and mixed it with γ-glycerol methoxytrimethoxysilane (GPTMS) to prepare CYC-ß-cyclodextrin (ßCD)/GPTMS film by sol-gel. The chemical structure of CYC-ßCD was confirmed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The chemical characterization of CYC-ßCD/GPTMS film was performed by differential scanning calorimetry, X-ray diffraction, and small-angle X-ray scattering. The surface morphology and phase separation microstructure of the film were determined by scanning electron microscopy and atomic force microscopy, and the image of polarizing microscopy showed the liquid-crystal structure of the film. Cell culture experiments showed that CYC-ßCD/GPTMS film had good cytocompatibility and induced growth and proliferation of cells. These results indicated the potential applications of CYC-ßCD/GPTMS film in tissue engineering scaffolds.

TRIM34 modulates influenza virus-activated programmed cell death by targeting Z-DNA-binding protein 1 for K63-linked polyubiquitination.

Z-DNA-binding protein 1 (ZBP1) is an innate sensor of influenza A virus (IAV) that participates in IAV-induced programmed cell death. Nevertheless, little is known about the upstream signaling pathways regulating ZBP1. We found that a member of the tripartite motif (TRIM) family, TRIM34, interacted with ZBP1 to promote its K63-linked polyubiquitination. Using a series of genetic approaches, we provide in vitro and in vivo evidence indicating that IAV triggered cell death and inflammatory responses via dependent on TRIM34/ZBP1 interaction. TRIM34 and ZBP1 expression and interaction protected mice from death during IAV infection owing to reduced inflammatory responses and epithelial damage. Additionally, analysis of clinical samples revealed that TRIM34 associates with ZBP1 and mediates ZBP1 polyubiquitination in vivo. Higher levels of proinflammatory cytokines correlated with higher levels of ZBP1 in IAV-infected patients. Taken together, we conclude that TRIM34 serves as a critical regulator of IAV-induced programmed cell death by mediating the K63-linked polyubiquitination of ZBP1.

ECMO combined with prone positioning strategies in COVID-19 respiratory distress syndrome.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already become a global pandemic as a public health emergency of international concern. Previous evidence from similar patient populations proved that carefully selected patients with severe ARDS who did not benefit from conventional treatment might be successfully supported with Veno-Venous extracorporeal membrane oxygenation (V-V ECMO). We now share the case reports of COVID-19 patients with ECMO combined prone position strategies.

Erratum: MicroRNA-183 suppresses the vitality, invasion and migration of human osteosarcoma cells by targeting metastasis-associated protein 1.

[This corrects the article DOI: 10.3892/etm.2018.6068.].

Modulation of neo-endothelialization of vascular graft materials by silk fibroin.

Controlled neo-endothelialization is critical to the patency of vascular grafts. Expanded polyethylene terephthalate (PET) vascular grafts were grafted with polyethylene glycol (PEG), irradiated with ultraviolet light, and subsequently coated with silk fibroin (SF) and EDC in a dip-coating process. Endothelial cells were cultivated on the coated samples for 1, 3, 5, and 7 days, and characterized by fluorescence microscopy and scanning electron microscopy (SEM). The quantitative analyse of CCK-8 method was used to assess ECs proliferation. The results reveal the correlation between grafting components and cell adhesion. We demonstrated that PET with SF grafting facilitated cell adhesion and spreading. Following 7 days of cell culture in vitro, PET-PEG6000-SF (PEG molecular weight 6,000) displayed spreading of cells over a significantly larger area. Rapid endothelialization on a modified PET surface resulted in large tissue pack that can be observed by SEM.

Blocking circ-SCMH1 (hsa_circ_0011946) suppresses acquired DDP resistance of oral squamous cell carcinoma (OSCC) cells both in vitro and in vivo by sponging miR-338-3p and regulating LIN28B.

BACKGROUND: Circular RNAs (circRNAs) could participate in cis-dichlorodiammineplatinum (DDP) resistance of human cancers. However, circRNAs role in DDP resistance of oral squamous cell carcinoma (OSCC) progression remains largely undeveloped. Here, we attempted to explore the role of circ-SCMH1 (ID hsa_circ_0011946) in acquired DDP resistance. METHODS: Expression of circ-SCMH1, microRNA (miR)-338-3p and Lin-28 homolog B (LIN28B) was detected by real-time quantitative PCR and western blotting, and their interactions were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay. DDP resistance was assessed by MTT assay, colony formation assay, flow cytometry, transwell assays, western blotting, and xenograft experiment. Transmission electron microscopic analysis, nanoparticle tracking analysis and western blotting confirmed the characterizations of extracellular vesicles (EVs). RESULTS: Circ-SCMH1 was upregulated in DDP-resistant OSCC tissues and cells (SCC-15/DDP and CAL-27/DDP). Circ-SCMH1 knockdown suppressed the half-maximal inhibitory concentration of DDP, colony formation, and migration/invasion in SCC-15/DDP and CAL-27/DDP cells, but promoted apoptosis rate and apoptotic proteins (Bax and cleaved-caspase-3) expression. However, silencing miR-338-3p abrogated above effects, and overexpressing miR-338-3p mimicked that. Similarly, miR-338-3p overexpression role could be counteracted by restoring LIN28B. Moreover, interfering circ-SCMH1 retarded tumor growth of SCC-15/DDP cells in vivo with DDP treatment or not. Mechanistically, circ-SCMH1 directly sponged miR-338-3p in regulating LIN28B, a target gene for miR-338-3p. Notably, circ-SCMH1 was an EVs cargo, and DDP-resistant OSCC cells-derived EVs could provoke circ-SCMH1 upregulation in parental cells. CONCLUSION: Circ-SCMH1 contributes to chemoresistance of DDP-resistant OSCC cells partially via EVs secretion and circ-SCMH1/miR-338-3p/LIN28B axis.

Long non-coding RNA CASC9/microRNA-590-3p axis participates in lutein-mediated suppression of breast cancer cell proliferation.

Previous studies have shown that lutein can inhibit the proliferation of breast cancer cells. However, the mechanism of lutein inhibiting the proliferation of breast cancer cells remains unclear. The present study aimed to determine whether the long non-coding RNA (lncRNA) Cancer Susceptibility 9 (CASC9)/microRNA (miR)-590-3p axis participates in the antiproliferative effects of lutein via lncRNA microarray hybridization, reverse transcription-quantitative PCR, dual-luciferase reporter and MTT assays. The results demonstrated that CASC9 was the most significantly downregulated lncRNA in MCF7 cells treated with lutein. miR-590-3p was identified as the target of CASC9. In addition, lutein downregulated CASC9 expression and upregulated miR-590-3p expression in dose- and time-dependent manners, respectively. CASC9 knockdown or overexpression of miR-590-3p inhibited the proliferation of breast cancer cells. Notably, simultaneous transfection with miR-590-3p mimics and CASC9 small interfering RNA increased the potency of lutein in inhibiting the proliferation of breast cancer cells. Taken together, these results suggest that the CASC9/miR-590-3p axis participates in the antiproliferative effects of lutein on breast cancer.

Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway.

BACKGROUND: Solute carrier family 6 member 14 (SLC6A14) is a high-capacity amino acid transporter in mammalian cells. It has gained increasing attention for its potential involvement in the progression and metabolic reprogramming of various malignant tumors. However, the role of SLC6A14 in colorectal cancer (CRC) remains unclear. METHODS: Real-time polymerase chain reaction (qRT-PCR), immunoblotting and immunohistochemistry were carried out to detect the expression level of SLC6A14 in human CRC tissues and CRC-derived cell lines. HCT-116 and Caco-2 cell lines were selected to conduct in vitro functional studies. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, cell migration and invasion assays were performed to investigate the role of SLC6A14 in CRC cells. Besides, azoxymethane/dextran sulfate sodium salt (AOM/DSS)-induced CRC and tumor xenograft models were constructed to explore the effects of SLC6A14 blockade or overexpression during tumor progression in vivo. RESULTS: SLC6A14 was substantially increased in human CRC samples and higher levels of SLC6A14 was correlated with advanced tumor stage, lymph node metastasis and dismal survival of CRC patients. SLC6A14 markedly promoted cell growth, inhibited cell apoptosis, and exacerbated migration and invasion of CRC cells in vitro. Mechanistically, SLC6A14 aggravated these malignant phenotypes through activating JAK2/STAT3 signaling pathway, and inhibiting JAK2/STAT3 signaling with specific inhibitors could reverse SLC6A14-mediated tumorigenic effects. Besides, two different animal studies verified the tumor-promoting effect of SLC6A14 in CRC. CONCLUSION: Our data illustrated the crucial function of SLC6A14 during CRC progression, suggesting SLC6A14/JAK2/STAT3 axis may serve as novel therapeutic targets for patients with CRC.

Protective and anti-inflammatory role of REG1A in inflammatory bowel disease induced by JAK/STAT3 signaling axis.

Regenerating islet-derived protein 1-alpha (REG1A) was abnormally upregulated in a series of gastrointestinal inflammatory disorders. However, the potential biological function and underlying regulatory mechanisms of the increased REG1A in inflammatory bowel disease (IBD) pathogenesis remain to be fully elucidated. In this study, we uncovered that REG1A was substantially increased in the inflamed colorectal tissues of IBD patients. And the aberrantly expressed REG1A in intestinal epithelial cells (IEC) prominently inhibited inflammatory responses, promoted cell proliferation and suppressed epithelial apoptosis. Mechanically, IL-6 and IL-22 markedly activated REG1A transcription through triggering JAK/STAT3 signaling pathway. In addition, overexpression of REG1A in mice by systematic delivery of REG1A lentivirus remarkably alleviated DSS-induced inflammatory injury and maintained the integrity of intestinal mucosal barrier. Taken together, our data demonstrated that the novel proliferative factor REG1A controlled by IL-6/IL-22-JAK-STAT3 signaling may provide a promising therapeutic target for patients with IBD.