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Exposure to microgravity can adversely affect the fitness of astronauts. The integrity of the skin plays a crucial role in protecting against mechanical forces and infections, fluid imbalance, and thermal dysregulation. In brief, the skin wound may cause unknown challenges to the implementation of space missions. Wound healing is a physiological process that relies on the synergistic action of inflammatory cells, extracellular matrix (ECM), and various growth factors to maintain the integrity of skin after trauma. Fibroblasts are present almost throughout the entire process of wound repair, especially in the scar formation at the endpoint of wound healing. However, there is limited knowledge about the extent to which fibroblasts are affected by the lack of gravity during wound healing. In this study, we utilized the rotary cell culture system, a ground-based facility that mimics the weightless condition, to study the alterations of L929 fibroblast cells under simulated microgravity (SMG). Our results demonstrated that the SM condition exerted negative influences on the proliferation and ECM formation of the L929 fibroblast. Whereas, the apoptosis of fibroblast was significantly upregulated upon exposure to SMG conditions. Moreover, the transforming growth factor-ß1/Smad3 (TGF-ß1/smad3) signaling pathway of L929 fibroblast related to wound repair was also altered significantly under a weightless environment. Overall, our study provided evidence that fibroblasts are strongly sensitive to SMG and elucidated the potential value of the TGF-ß1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.
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Fator de Crescimento Transformador beta1 , Ausência de Peso , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Transdução de Sinais , Matriz Extracelular , Apoptose , Proliferação de Células , Fibroblastos/metabolismo , Proteína Smad3/metabolismoRESUMO
Objectives: Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study is a meta-analysis undertaken to estimate the prognosis and survival associated with CTNNB1/ß-catenin, APC, Wnt, SMAD3/4, TP53, and Cyclin D1 genes among CRC patients. Methods: The authors searched PubMed, EMBASE, and Science Direct for relevant reports published between 2000 and 2020 and analyzed them to determine any relationship between the (immunohistochemically/sequencing-detected) gene expression and variants of the selected genes and the survival of CRC patients. Results: The analysis included 34,074 patients from 64 studies. To evaluate association, hazard ratios (HRs) were estimated for overall survival (OS) or disease-free survival (DFS), with a 95% confidence interval (CIs). Pooled results showed that ß-catenin overexpression, APC mutation, SMAD-3 or 4 loss of expression, TP53 mutations, and Cyclin D1 expression were associated with shorter OS. ß-Catenin overexpression (HR: 0.137 (95% CI: 0.131-0.406)), loss of expression of SMAD3 or 4 (HR: 0.449 (95% CI: 0.146-0.753)), the mutations of TP53 (HR: 0.179 (95% CI: 0.126-0.485)), and Cyclin D1 expression (HR: 0.485 (95% CI: 0.772-0.198)) also presented risk for shorter DFS. Conclusions: The present meta-analysis indicates that overexpression or underexpression and variants of CTNNB1/ß-catenin, APC, SMAD3/4, TP53, and Cyclin D1 genes potentially acted as unfavorable biomarkers for the prognosis of CRC. The Wnt gene was not associated with prognosis.
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Neoplasias Colorretais , beta Catenina , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Genes bcl-1 , Humanos , Prognóstico , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteína Supressora de Tumor p53/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Macroautophagy/autophagy plays an important role in regulating cellular homeostasis and influences the pathogenesis of degenerative diseases. Tendinopathy is characterized by tendon degeneration and inflammation. However, little is known about the role of selective autophagy in tendinopathy. Here, we find that pristimerin (PM), a quinone methide triterpenoid, is more effective in treating tendinopathy than the first-line drug indomethacin. PM inhibits the AIM2 inflammasome and alleviates inflammation during tendinopathy by promoting the autophagic degradation of AIM2 through a PYCARD/ASC-dependent manner. A mechanistic study shows that PM enhances the K63-linked ubiquitin chains of PYCARD/ASC at K158/161, which serves as a recognition signal for SQSTM1/p62-mediated autophagic degradation of the AIM2-PYCARD/ASC complex. We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC. Finally, PM treatment in vivo generates an effect comparable to inflammasome deficiency in alleviating tendinopathy. Taken together, these findings demonstrate that PM alleviates the progression of tendinopathy by modulating AIM2-PYCARD/ASC stability via SQSTM1/p62-mediated selective autophagic degradation, thus providing a promising autophagy-based therapeutic for tendinopathy.Abbreviations: 3-MA: 3-methyladenine; AIM2: absent in melanoma 2; AT: Achilles tenotomy; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CHX: cycloheximide; Col3a1: collagen, type III, alpha 1; CQ: chloroquine; Cys: cysteine; DARTS: drug affinity responsive target stability; DTT: dithiothreitol; DUB: deubiquitinase; gDNA: genomic DNA; GSH: glutathione; His: histidine; IL1B/IL-1ß: interleukin 1 beta; IND: indomethacin; IP: immunoprecipitation; LPS: lipopolysaccharide; MMP: mitochondrial membrane potential; NLRP3: NLR family, pyrin domain containing 3; PM: pristimerin; PYCARD/ASC: PYD and CARD domain containing; SN: supernatants; SOX9: SRY (sex determining region Y)-box 9; SQSTM1: sequestosome 1; Tgfb: transforming growth factor, beta; TIMP3: tissue inhibitor of metalloproteinase 3; TNMD: tenomodulin; TRAF6: TNF receptor-associated factor 6; Ub: ubiquitin; USP50: ubiquitin specific peptidase 50; WCL: whole cell lysates.
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Inflamassomos , Tendinopatia , Humanos , Inflamassomos/metabolismo , Proteína Sequestossoma-1/metabolismo , Autofagia/genética , Macroautofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação , Ubiquitina/metabolismo , Indometacina/farmacologia , Enzimas Desubiquitinantes/metabolismo , Interleucina-1beta/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
Conventional two-dimensional (2D) cell culture techniques may undergo modifications in the future, as life scientists have widely acknowledged the ability of three-dimensional (3D) in vitro culture systems to accurately simulate in vivo biology. In recent years, researchers have discovered that microgravity devices can address many challenges associated with 3D cell culture. Stem cells, being pluripotent cells, are regarded as a promising resource for regenerative medicine. Recent studies have demonstrated that 3D culture in microgravity devices can effectively guide stem cells towards differentiation and facilitate the formation of functional tissue, thereby exhibiting advantages within the field of tissue engineering and regenerative medicine. Furthermore, We delineate the impact of microgravity on the biological behavior of various types of stem cells, while elucidating the underlying mechanisms governing these alterations. These findings offer exciting prospects for diverse applications.
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Medicina Regenerativa , Células-Tronco , Engenharia Tecidual , Ausência de Peso , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Humanos , Células-Tronco/citologia , Células-Tronco/fisiologia , Diferenciação Celular , Animais , Técnicas de Cultura de Células em Três Dimensões/métodos , Técnicas de Cultura de Células/métodosRESUMO
Microgravity is a primary challenge that need to overcome, when human travel to space. Our study provided evidence that Kupffer cells (KCs) are sensitive to simulated microgravity (SMG), and no similar research report has been found in the literature. Using transcriptome sequencing technology, it was showed that 631 genes were upregulated and 801 genes were downregulated in KCs after treatment under SMG for 3 days. The GO analysis indicated that the proliferation of KCs was affected when exposed to SMG for 3 days. CCK-8 assay confirmed that the proliferation of KCs was inhibited in the third day under the environment of SMG. Furthermore, we identified 8 key genes that affect the proliferation of KCs and predicted 2 transcription factors (TFs) that regulate the 8 key genes. Significantly, we found that microgravity could affect the expression of LMO2 and EZH2 to reduce the transcription of Racgap1, Ccna2, Nek2, Aurka, Plk1, Haus4, Cdc20, Bub1b, which resulting in the reduction in KCs proliferation. These finding suggested that the inhibition of KCs proliferation under microgravity may influence the homeostasis of liver, and LMO2 and EZH2 can be the targets in management of KCs' disturbance in the future practice of space medicine.
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Transcriptoma , Ausência de Peso , Humanos , Células de Kupffer , Proliferação de Células , Simulação de Ausência de Peso , Proteína Potenciadora do Homólogo 2 de Zeste , Proteínas Proto-Oncogênicas , Proteínas Adaptadoras de Transdução de Sinal , Proteínas com Domínio LIM/genéticaRESUMO
Toxoplasma gondii (T. gondii)-associated polymorphic effector proteins are crucial in parasite development and regulating host anti-T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN-I activation. Infection with Δgra4 mutant T. gondii strain induces stronger IFN-I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27-catalyzed K48-ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent Δgra4 strain (ME49Δompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN-I production. Earlier vaccination with ME49Δompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49Δompdc treatment. Notably, ME49Δompdc/gra4 vaccination induces a specific CD64+MAR-1+CD11b+ dendritic cell subset, thereby enhancing T cell anti-tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN-I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.
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Stringent control of type I interferon (IFN-I) signaling is critical to potent innate immune responses against viral infection, yet the underlying molecular mechanisms are still elusive. Here, we found that Van Gogh-like 2 (VANGL2) acts as an IFN-inducible negative feedback regulator to suppress IFN-I signaling during vesicular stomatitis virus (VSV) infection. Mechanistically, VANGL2 interacted with TBK1 and promoted the selective autophagic degradation of TBK1 via K48-linked polyubiquitination at Lys372 by the E3 ligase TRIP, which serves as a recognition signal for the cargo receptor OPTN. Furthermore, myeloid-specific deletion of VANGL2 in mice showed enhanced IFN-I production against VSV infection and improved survival. In general, these findings revealed a negative feedback loop of IFN-I signaling through the VANGL2-TRIP-TBK1-OPTN axis and highlighted the cross-talk between IFN-I and autophagy in preventing viral infection. VANGL2 could be a potential clinical therapeutic target for viral infectious diseases, including COVID-19.
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Interferon Tipo I , Proteínas Serina-Treonina Quinases , Viroses , Animais , Camundongos , Autofagia , Polaridade Celular , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição , Viroses/imunologia , Interferon Tipo I/imunologiaRESUMO
Stringent control of the type I interferon (IFN-I) signaling is critical for host immune defense against infectious diseases, yet the molecular mechanisms that regulate this pathway remain elusive. Here, we show that Src homology 2 containing inositol phosphatase 1 (SHIP1) suppresses IFN-I signaling by promoting IRF3 degradation during malaria infection. Genetic ablation of Ship1 in mice leads to high levels of IFN-I and confers resistance to Plasmodium yoelii nigeriensis (P.y.) N67 infection. Mechanistically, SHIP1 promotes the selective autophagic degradation of IRF3 by enhancing K63-linked ubiquitination of IRF3 at lysine 313, which serves as a recognition signal for NDP52-mediated selective autophagic degradation. In addition, SHIP1 is downregulated by IFN-I-induced miR-155-5p upon P.y. N67 infection and severs as a feedback loop of the signaling crosstalk. This study reveals a regulatory mechanism between IFN-I signaling and autophagy, and verifies SHIP1 can be a potential target for therapeutic intervention against malaria and other infectious diseases. IMPORTANCE Malaria remains a serious disease affecting millions of people worldwide. Malaria parasite infection triggers tightly controlled type I interferon (IFN-I) signaling that plays a critical role in host innate immunity; however, the molecular mechanisms underlying the immune responses are still elusive. Here, we discover a host gene [Src homology 2-containing inositol phosphatase 1 (SHIP1)] that can regulate IFN-I signaling by modulating NDP52-mediated selective autophagic degradation of IRF3 and significantly affect parasitemia and resistance of Plasmodium-infected mice. This study identifies SHIP1 as a potential target for immunotherapies in malaria and highlights the crosstalk between IFN-I signaling and autophagy in preventing related infectious diseases. SHIP1 functions as a negative regulator during malaria infection by targeting IRF3 for autophagic degradation.
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Hepatic macrophages are a complex population of cells that play an important role in the normal functioning of the liver and in liver diseases. Autophagy, as a maintainer of cellular homeostasis, is closely connected to many liver diseases. And its roles are not always beneficial, but manifesting as a double-edged sword. The polarization of macrophages and the activation of inflammasomes are mediated by intracellular and extracellular signals, respectively, and are important ways for macrophages to take part in a variety of liver diseases. More attention should be paid to autophagy of hepatic macrophages in liver diseases. In this review, we focus on the regulatory role of hepatic macrophages' autophagy in a variety of liver diseases; especially on the upstream regulator of polarization and inflammasomes activation of the hepatic macrophages. We believe that the autophagy of hepatic macrophages can become a potential therapeutic target for management of liver diseases.
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Inflamassomos , Hepatopatias , Humanos , Hepatopatias/terapia , Fígado , Macrófagos , AutofagiaRESUMO
Introduction: Recent studies have revealed that several deubiquitinating enzymes (DUBs) play important roles in hepatocellular carcinoma (HCC) progression, but the roles of Otubain 2 (OTUB2) in HCC remain obscure. Methods: In this study, we investigated the expression of OTUB2 in HCC based on clinical samples and a public online database (ENCORI), and its roles and working mechanisms were further explored by in vitro experiments. Results: It was found that the expression of OTUB2 was significantly up-regulated in HCC tissues, and correlated with poor prognosis of HCC patients. Functionally, the overexpression of OTUB2 could promote malignant proliferation and metastasis of HCC cells, while knockdown of OTUB2 exerted the opposite results. Using two bioinformatics tools, PJA1 was identified as a potential gene regulated by OTUB2. Mechanistically, it was found that OTUB2 promoted the stabilization of PJA1 by deubiquitylation, based on immunoprecipitation (IP) and cycloheximide (CHX) assays. Moreover, the suppressive effects of OTUB2 depletion on the malignant phenotypes of HCC cells could be reversed by overexpressing PJA1. Conclusion: In conclusion, our study indicated that OTUB2 could promote the malignant proliferation and migration of HCC cells by increasing the stability of PJA1 via deubiquitylation.
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BACKGROUND: Stomach adenocarcinomas (STAD) are the most common malignancy of the human digestive system and represent the fourth leading cause of cancer-related deaths. As early-stage STAD are generally mild or asymptomatic, patients with advanced STAD have short overall survival. Early diagnosis of STAD has a considerable influence on clinical outcomes. METHODS: The mRNA expression data and clinical indicators of STAD and normal tissues were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The gene expression differences were analyzed by R packages, and gene function enrichment analysis was performed. Kaplan-Meier method and univariate Cox proportional risk regression analysis were used to screen differential expressed genes (DEGs) related to survival of STAD patients. Multivariate Cox proportional risk regression analysis was used to further screen and determine the prognostic DEGs in STAD patients, and to construct a multigene prognostic prediction signature. The accuracy of predictive signature was tested by receiver operating characteristic (ROC) curve software package, and the nomogram of patients with STAD was drawn. Cox regression was used to investigate the correlation between multigene prognostic signature and clinical factors. The predictive performance of this model was compared with two other models proposed in previous studies using KM survival analysis, ROC curve analysis, Harrell consistency index and decision curve analysis (DCA). qRT-PCR and Western blot were used to verify the expression levels of prognostic genes. The pathways and functions of possible involvement of features were predicted using the GSEA method. RESULTS: A total of 569 early-stage specific DEGs were retrieved from TCGA-STAD dataset, including 229 up-regulated genes and 340 down-regulated genes. Enrichment analysis showed that the early-stage specific DEGs were associated with cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium signaling pathway. Multiple Cox regression algorithm was used to identify 10 early-stage specific DEGs associated with overall survival (P < 0.01) of STAD patients, and a multi-mRNA prognosis signature was established. The patients were divided into high-risk group and low-risk group according to the risk score. In the training set, the prognostic signature was positively correlated with tumor size and stage (P < 0.05), survival curve (P < 0.001) and time-dependent ROC (AUC = 0.625). In the training dataset and test dataset, the both signatures had good predictive efficiencies. Cox regression and DCA analysis revealed that the prognostic signature was an independent factor and had a better predict effect than the conventional TNM stage classification method and the earlier published biomarkers on the prognosis of STAD patients. CONCLUSION: In this study, based on the early-stage specifically expressed genes, the prognostic signature constructed through TCGA and GEO datasets may become an indicator for clinical prognosis assessment of STAD and a new strategy for targeted therapy in the future.
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Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Humanos , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Citocinas , Ligantes , Prognóstico , Receptores de Citocinas , RNA Mensageiro/genética , Estômago/patologia , Neoplasias Gástricas/genéticaRESUMO
Background: Intussusception is a rare clinical condition in adults. The majority of patients present with symptoms of bowel obstruction. Intussusception is often misdiagnosed and the majority of cases are diagnosed intraoperatively. In this paper, we present a rare case of adult jejunojejunal intussusception with chronic bleeding caused by a gastrointestinal stromal tumor (GIST). We emphasize the role of contrast-enhanced computed tomography (CT) and enteroscopy in the presurgical diagnosis and the good prognosis in the high-risk GIST patient after surgery and targeted therapy. Case Description: Herein, we present the case of a 63-year-old female patient with small bowel intussusception with chronic bleeding caused by a GIST. Her main symptoms were intermittent melena and progressive anemia. She had a 20-year history of hypertension and had never undergone previous abdominal surgery. After failure of an esophagogastroduodenoscopy and colonoscopy to locate the hemorrhagic foci in the gastrointestinal tract, contrast-enhanced CT and enteroscopy were used and a small bowel intussusception and an intraluminal mass with a bleeding ulcer was identified. The patient underwent laparoscopic partial small bowel resection, and postoperative pathological examinations showed a small intestinal GIST with a high risk of recurrence. It was suggested that the patient take imatinib regularly for at least 3 years. At the time of writing, she has remained in good health without relapse for 24 months after discharge. We also review 20 published cases of intussusception caused by small bowel GIST in the PubMed database. Conclusions: Obscure gastrointestinal hemorrhage needs meticulous examinations to promptly determine the cause and location of bleeding. This case and literature review revealed that comprehensive surgical resection-centered treatment was the standard treatment for primary localized GISTs in patients at significant risk of relapse.
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Innate immunity acts as the first line of defense against pathogen invasion. During Toxoplasma gondii infection, multiple innate immune sensors are activated by invading microbes or pathogen-associated molecular patterns (PAMPs). However, how inflammasome is activated and its regulatory mechanisms during T. gondii infection remain elusive. Here, we showed that the infection of PRU, a lethal type II T. gondii strain, activates inflammasome at the early stage of infection. PRU tachyzoites, RNA and soluble tachyzoite antigen (STAg) mainly triggered the NLRP3 inflammasome, while PRU genomic DNA (gDNA) specially activated the AIM2 inflammasome. Furthermore, mice deficient in AIM2, NLRP3, or caspase-1/11 were more susceptible to T. gondii PRU infection, and the ablation of inflammasome signaling impaired antitoxoplasmosis immune responses by enhancing type I interferon (IFN-I) production. Blockage of IFN-I receptor fulfilled inflammasome-deficient mice competent immune responses as WT mice. Moreover, we have identified that the suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator induced by inflammasome-activated IL-1ß signaling and inhibits IFN-I production by targeting interferon regulatory factor 3 (IRF3). In general, our study defines a novel protective role of inflammasome activation during toxoplasmosis and identifies a critical regulatory mechanism of the cross talk between inflammasome and IFN-I signaling for understanding infectious diseases. IMPORTANCE As a key component of innate immunity, inflammasome is critical for host antitoxoplasmosis immunity, but the underlying mechanisms are still elusive. In this study, we found that inflammasome signaling was activated by PAMPs of T. gondii, which generated a protective immunity against T. gondii invasion by suppressing type I interferon (IFN-I) production. Mechanically, inflammasome-coupled IL-1ß signaling triggered the expression of negative regulator SOCS1, which bound to IRF3 to inhibit IFN-I production. The role of IFN-I in anti-T. gondii immunity is little studied and controversial, and here we also found IFN-I is harmful to host antitoxoplasmosis immunity by using knockout mice and recombinant proteins. In general, our study identifies a protective role of inflammasomes to the host during T. gondii infection and a novel mechanism by which inflammasome suppresses IFN-I signaling in antitoxoplasmosis immunity, which will likely provide new insights into therapeutic targets for toxoplasmosis and highlight the cross talk between innate immune signaling in infectious diseases prevention.
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Doenças Transmissíveis , Interferon Tipo I , Toxoplasma , Toxoplasmose , Animais , Camundongos , Inflamassomos , Toxoplasma/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Moléculas com Motivos Associados a Patógenos , Imunidade Inata , Camundongos KnockoutRESUMO
Microgravity is an ecological factor that affects the environment of the body. In this study, quantitative isobaric labeling (tandem mass tag) method was used to study the changes in human gastric mucosal cells under simulated microgravity for the first time. Comparative proteomic analysis identified 394 (202 upregulated and 192 downregulated) and 542 (286 upregulated and 256 downregulated) proteins differentially regulated by simulated microgravity after 3 and 7 days, respectively. Then the identified proteins were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for further exploration. The results of the analysis showed that the ribosomes of gastric mucosal cells were significantly impacted after exposure to simulated microgravity for 3 days, and the cells appeared to be in a state of stress and inflammation. Exposure to simulated microgravity for 7 days significantly affected the mitochondria of the cells, oxidative stress became more evident, while inflammation and weakened connections were observed in the cells. The results of this study highlighted the temporal response trend of gastric mucosal cells to the stressor of microgravity at the two time points of 3 and 7 days. These findings will provide insights into the development of methods to protect the gastric mucosa during space flight.
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Voo Espacial , Ausência de Peso , Mucosa Gástrica , Humanos , Proteômica , Simulação de Ausência de PesoRESUMO
Torsion of an epiploic appendage may result in epiploic appendagitis, which is a rare cause of acute abdominal pain. However, no previous reports have described an asymptomatic twisted epiploic appendage found during laparoscopaic surgery to the best of our knowledge. This case describes a 66-year-old man who was admitted to our medical center with yellowness of the skin and eyes that had lasted over two months. Physical examination showed slight yellow staining of the skin and sclera. Blood analysis indicated liver dysfunction and jaundice. Routine blood, C-reactive protein (CRP), and levels of tumor markers were normal. The contrast-enhanced abdominal and pelvic computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed gallbladder atrophy and choledocholithiasis. The patient underwent laparoscopic surgery for the removal of the choledocholithiasis. The laparoscopic exploration unexpectedly revealed a twisted and ischemic epiploic appendage, which was surgically removed. The postoperative pathological examination uncovered necrosis of adipocytes and vascular obstruction, but there was no inflammation of the epiploic appendage. The patient had a satisfactory recovery during the 16-month follow-up period. This case describes and provides a feasible management approach for an asymptomatic twisted epiploic appendage discovered during surgery and highlights its pathological characteristics, reflecting the early stage of epiploic appendagitis.
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Dor Abdominal , Laparoscopia , Idoso , Colo , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
Astronauts suffer from inflammatory changes induced by microgravity during space flight. Microgravity can significantly affect the inflammatory response of various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and digestive system. The aim of this research was to identify the key genes and pathways of gastric mucosa affected by microgravity. Human gastric mucosal epithelial GES-1 cells were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The gene expression profiles of GES-1 cells were obtained using Illumina sequencing platform and differentially expressed genes were identified by DESeq2 software, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Subsequently, a protein-protein interaction (PPI) network was constructed. Compared with a normal gravity (NG) group, a total of 943 DEGs, including 192 downregulated genes and 751 upregulated genes, were identified. These DEGs were associated with findings that included response to interleukin-1, positive regulation of inflammatory response, and positive regulation of neuroinflammatory response. Furthermore, these DEGs were mainly enriched in herpes simplex virus 1 infection, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathway. Thus, 21 hub genes were identified from PPI network, including IL6, IL1B, ITGAM, CXCL8, ITGAX, CCL5, SERPINA1, APOE, CSF1R, VWF, GBP1, APOB, CYBB, HLA-DRB1, CD68, FGG, FGA, OASL, NOD2, OAS2 and FCGR2A. These findings suggested that simulated microgravity upregulated inflammation-related genes and pathways of GES-1 cells, which may play important roles in the response to microgravity and provide useful information for preventing mucosal damage in astronauts. In conclusion, this study revealed the key genes and pathways associated with simulated microgravity and indicated that simulated microgravity induced an inflammatory response in gastric mucosal epithelial cells.
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The composition and function of intestinal microbial communities are important for human health. However, these intestinal floras are sensitive to changes in the environment. Adverse changes to intestinal flora can affect the health of astronauts, resulting in difficulties in implementing space missions. We randomly divided mice into three groups and placed each group in either a normal environment, simulated microgravity environment or a combined effects environment, which included simulated microgravity, low pressure and noise. Fecal samples of the mice were collected for follow-up analysis based on metagenomics technology. With the influence of different space environmental factors, the species composition at the phylum and genus levels were significantly affected by the combined effects environment, especially the abundance of the Firmicutes and Bacteroidetes. Furthermore, screening was conducted to identify biomarkers that could be regarded as environmental markers. And there have also been some noticeable changes in the function of intestinal floras. Moreover, the abundance of antibiotic resistance genes (ARGs) was also found to be changed under different environmental conditions, such as bacitracin and vancomycin. The combined effects environment could significantly affect the species composition, function, and the expression of ARGs of intestinal flora of mice which may provide a theoretical basis for space medical supervision and healthcare.
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Astronautas , Microbioma Gastrointestinal , Simulação de Ausência de Peso , Animais , Biomarcadores/metabolismo , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.
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Autofagia , Mucosa Gástrica/patologia , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/complicações , Helicobacter pylori/efeitos dos fármacos , Homeostase , Humanos , Inflamação , Lisossomos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Inibidores da Bomba de Prótons/farmacologia , Espécies Reativas de Oxigênio , Úlcera Gástrica/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Weightlessness is a component of the complex space environment. It exerts adverse effects on the human body, and may pose unknown challenges to the implementation of space missions. The regular function of the digestive system is an important checkpoint for astronauts to conduct missions. Simulated microgravity can recreate the changes experienced by the human body in a weightless environment in space to a certain extent, providing technical support for the exploration of its mechanism and a practical method for other scientific research. METHODS AND MATERIALS: In the present study, we reviewed and discussed the latest research on the effects of weightlessness or simulated microgravity on the digestive system, as well as the current challenges and future expectations for progress in medical science and further space exploration. RESULTS: A series of studies have investigated the effects of weightlessness on the human digestive system. On one hand, weightlessness and the changing space environment may exert certain adverse effects on the human body. Studies based on cells or animals have demonstrated the complex effects on the human digestive system in response to weightlessness. On the other hand, a microgravity environment also facilitates the ideation of novel concepts for research in the domain of life science. CONCLUSION: The effects of weightlessness on the digestive system are considerably complicated. The emergence of methods that help simulate a weightless environment provides a more convenient alternative for assessing the impact and the mechanism underlying the effect of weightlessness on the human body. In addition, the simulated microgravity environment facilitates the ideation of novel concepts for application in regenerative medicine and other fields of life science.
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Disciplinas das Ciências Biológicas , Voo Espacial , Ausência de Peso , Animais , Astronautas , Sistema Digestório , Humanos , Ausência de Peso/efeitos adversosRESUMO
Rutinose and five R-beta-rutinosides were obtained by means of rutin-degrading reaction in water or aqueous alcohol (ROH, R = methyl, ethyl, propyl, isopropyl, and benzyl) with rutin-degrading enzyme as catalyst and rutin as starting material in 84-94% yields, of which methyl-beta-rutinoside, propyl-beta-rutinoside, isopropyl-beta-rutinoside, and benzyl-beta-rutinoside are firstly reported in this paper. Based on spectral analysis, the structures of all products were elucidated.