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Yu CP, Lin IJ, Wang BL, Tsao CH, Huang SH, Huang YC, Sun CA, Chung CH, Hu JM, Chien WC. Intestinal infectious diseases increase the risk of psychiatric disorders: A nationwide population-based cohort study. Medicine (Baltimore) 2022; 101:e30959. [PMID: 36221435 PMCID: PMC9543017 DOI: 10.1097/md.0000000000030959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Intestinal infectious diseases (IIDs) are among the most common diseases and are prevalent worldwide. IIDs are also one of the major disease groups with the highest incidence worldwide, especially among children and older adults. We observed a higher probability of IIDs in patients from the psychiatric department of Tri-Service General Hospital. Therefore, our objective was to investigate if there is an association between IIDs and the risk of developing psychiatric disorders. This nationwide population-based study used the database of the National Health Insurance (NHI) program in Taiwan. The study included 150,995 patients from 2000 to 2015, comprising 30,199 patients with IIDs as the study group and 120,796 patients without IIDs as the control group. Cox proportional hazards regression analysis was performed to calculate the hazard ratio of psychiatric disorders during the 16-year follow-up. Of the patients with IIDs, 4022 (13.32%) developed psychiatric disorders compared to 8119 (6.72%) who did not (P < .001). The adjusted hazard ratio (aHR) for overall psychiatric disorders in the study group was 2.724 (95% confidence interval [CI]: 2.482-2.976; P < .001). More specifically, the study group had a higher risk of developing a psychiatric disorder, including sleep disorders, depression, anxiety, bipolar disorder, post-traumatic stress disorder (PTSD)/acute stress disorder (ASD), schizophrenia, mental retardation (MR), substance abuse, and other psychiatric disorders. Furthermore, refractory IIDs (seeking medical attention for IIDs 3 or more times) increased the risk (aHR: 3.918; 95% CI: 3.569-4.280; P < .001) of developing psychiatric disorders. There was an association between IIDs and the increased risk of developing psychiatric disorders. The novel role of etiological factors in the development of psychiatric disorders deserves more attention, and the control of pathogens that cause IIDs is of urgent public health importance.
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Affiliation(s)
- Chia-Peng Yu
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Iau-Jin Lin
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Bing-Long Wang
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Huei Tsao
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan
| | - Shi-Hao Huang
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan
| | - Yao-Ching Huang
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan
| | - Chien-An Sun
- Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
- Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
| | - Je-Ming Hu
- Division of Colorectal Surgery, Department of surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- *Correspondence: Wu-Chien Chien, Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan and Je-Ming Hu, Division of Colorectal Surgery, Department of surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan (e-mail: (W-CC) and (J-MH))
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
- *Correspondence: Wu-Chien Chien, Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan and Je-Ming Hu, Division of Colorectal Surgery, Department of surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan (e-mail: (W-CC) and (J-MH))
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Pourhassan N Z, Smits SHJ, Ahn JH, Schmitt L. Biotechnological applications of type 1 secretion systems. Biotechnol Adv 2021; 53:107864. [PMID: 34767962 DOI: 10.1016/j.biotechadv.2021.107864] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/30/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023]
Abstract
Bacteria have evolved a diverse range of secretion systems to export different substrates across their cell envelope. Although secretion of proteins into the extracellular space could offer advantages for recombinant protein production, the low secretion titers of the secretion systems for some heterologous proteins remain a clear drawback of their utility at commercial scales. Therefore, a potential use of most of secretion systems as production platforms at large scales are still limited. To overcome this limitation, remarkable efforts have been made toward improving the secretion efficiency of different bacterial secretion systems in recent years. Here, we review the progress with respect to biotechnological applications of type I secretion system (T1SS) of Gram-negative bacteria. We will also focus on the applicability of T1SS for the secretion of heterologous proteins as well as vaccine development. Last but not least, we explore the employed engineering strategies that have enhanced the secretion efficiencies of T1SS. Attention is also paid to directed evolution approaches that may offer a more versatile approach to optimize secretion efficiency of T1SS.
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Affiliation(s)
- Zohreh Pourhassan N
- Institute of Biochemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
| | - Sander H J Smits
- Institute of Biochemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
| | - Jung Hoon Ahn
- Department of Chemistry and Biology, Korea Science Academy of Korea Advanced Institute of Science and Technology, Busan 47162, South Korea
| | - Lutz Schmitt
- Institute of Biochemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
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Panteli JT, Forbes NS. Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses. Biotechnol Bioeng 2016; 113:2474-84. [PMID: 27159665 DOI: 10.1002/bit.26006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 04/07/2016] [Accepted: 05/01/2016] [Indexed: 01/04/2023]
Abstract
Tumor heterogeneity makes cancer difficult to treat. Many small molecule cancer drugs target rapidly dividing cells on the periphery of tumors but have difficulty in penetrating deep into tumors and are ineffective at treating entire tumors. Targeting both rapidly dividing and slower growing regions of tumors is essential to effectively treat cancer. A cancer drug carrier that penetrates deep into tumors and identifies metabolically activity could supply treatment to those areas based on the local microenvironment. We hypothesized that glucose sensing bacteria could identify sugar gradients in solid tumors. To test this hypothesis, a genetic circuit was designed to trigger expression of a green fluorescent protein (GFP) reporter through the chemotaxis-osmoporin fusion protein, Trz1, a receptor for sensing glucose and ribose sugars. E. coli equipped with the Trz1-GFP expression system, were administered to an in vitro model of a continuously perfused tumor tissue that mimics systemic delivery and clearance of bacteria through a blood vessel adjacent to a solid tumor. The level of GFP expressed, per bacterium, was time independent and indicated the glucose concentration as a function of penetration depth within the microfluidic tumors. The measured glucose concentration, correlated (P-value = 2.6 × 10(-5) ) with tumor cell viability as a function of depth. Mathematical analysis predicted drug delivery by glucose-sensing bacteria would eliminate a higher percentage of the viable tumor cell population than a systemically administered drug. Glucose-sensing bacteria could deliver cancer therapies with increased drug penetration and nutrient-dependent dosing to continuously treat viable regions of cancer tissue that have a higher prevalence for metastatic dissemination. Biotechnol. Bioeng. 2016;113: 2474-2484. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Jan T Panteli
- Department of Chemical Engineering, University of Massachusetts, 686 North Pleasant Street, Amherst, Massachusetts, 01003
| | - Neil S Forbes
- Department of Chemical Engineering, University of Massachusetts, 686 North Pleasant Street, Amherst, Massachusetts, 01003.
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Recombinant Salmonella enterica serovar Typhimurium as a vaccine vector for HIV-1 Gag. Viruses 2013; 5:2062-78. [PMID: 23989890 PMCID: PMC3798890 DOI: 10.3390/v5092062] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Revised: 08/05/2013] [Accepted: 08/22/2013] [Indexed: 01/30/2023] Open
Abstract
The HIV/AIDS epidemic remains a global health problem, especially in Sub-Saharan Africa. An effective HIV-1 vaccine is therefore badly required to mitigate this ever-expanding problem. Since HIV-1 infects its host through the mucosal surface, a vaccine for the virus needs to trigger mucosal as well as systemic immune responses. Oral, attenuated recombinant Salmonella vaccines offer this potential of delivering HIV-1 antigens to both the mucosal and systemic compartments of the immune system. So far, a number of pre-clinical studies have been performed, in which HIV-1 Gag, a highly conserved viral antigen possessing both T- and B-cell epitopes, was successfully delivered by recombinant Salmonella vaccines and, in most cases, induced HIV-specific immune responses. In this review, the potential use of Salmonella enterica serovar Typhimurium as a live vaccine vector for HIV-1 Gag is explored.
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Akiho H, Ihara E, Motomura Y, Nakamura K. Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders. World J Gastrointest Pathophysiol 2011; 2:72-81. [PMID: 22013552 PMCID: PMC3196622 DOI: 10.4291/wjgp.v2.i5.72] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2011] [Revised: 08/12/2011] [Accepted: 08/19/2011] [Indexed: 02/06/2023] Open
Abstract
Inflammation and immune activation in the gut are usually accompanied by alteration of gastrointestinal (GI) motility. In infection, changes in motor function have been linked to host defense by enhancing the expulsion of the infectious agents. In this review, we describe the evidence for inflammation and immune activation in GI infection, inflammatory bowel disease, ileus, achalasia, eosinophilic esophagitis, microscopic colitis, celiac disease, pseudo-obstruction and functional GI disorders. We also describe the possible mechanisms by which inflammation and immune activation in the gut affect GI motility. GI motility disorder is a broad spectrum disturbance of GI physiology. Although several systems including central nerves, enteric nerves, interstitial cells of Cajal and smooth muscles contribute to a coordinated regulation of GI motility, smooth muscle probably plays the most important role. Thus, we focus on the relationship between activation of cytokines induced by adaptive immune response and alteration of GI smooth muscle contractility. Accumulated evidence has shown that Th1 and Th2 cytokines cause hypocontractility and hypercontractility of inflamed intestinal smooth muscle. Th1 cytokines downregulate CPI-17 and L-type Ca2+ channels and upregulate regulators of G protein signaling 4, which contributes to hypocontractility of inflamed intestinal smooth muscle. Conversely, Th2 cytokines cause hypercontractilty via signal transducer and activator of transcription 6 or mitogen-activated protein kinase signaling pathways. Th1 and Th2 cytokines have opposing effects on intestinal smooth muscle contraction via 5-hydroxytryptamine signaling. Understanding the immunological basis of altered GI motor function could lead to new therapeutic strategies for GI functional and inflammatory disorders.
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Lin CH, Hsieh CC, Chen SJ, Wu TC, Chung RL, Tang RB. The diagnostic value of serum interleukins 6 and 8 in children with acute gastroenteritis. J Pediatr Gastroenterol Nutr 2006; 43:25-9. [PMID: 16819373 DOI: 10.1097/01.mpg.0000235764.30743.5b] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Early identification of the pathogen causing acute gastroenteritis in children helps the physicians managing the disease and prevents unnecessary antibiotic treatment. C-reactive protein (CRP), interleukin (IL) 6 and IL-8 play a major role in immune responses and have been studied in a large number of infectious and noninfectious inflammatory diseases. The purpose of this study was to determine the serum IL-6 and IL-8 concentrations early in the course of acute gastroenteritis to see if these cytokines were useful diagnostic markers in differentiating viral from bacterial gastroenteritis. METHODS Interleukin 6, IL-8 and CRP were measured in 18 patients with bacterial gastroenteritis, 21 patients with viral gastroenteritis and 17 healthy children. RESULTS Interleukin 6 and CRP concentrations in patients with bacterial gastroenteritis were significantly higher than those in patients with viral gastroenteritis and healthy controls (P < 0.001). IL-8 concentrations in patients with viral and bacterial gastroenteritis were both increased and were not statistically different. IL-6 and IL-8 levels had diagnostic sensitivities of 79% and 50% and specificities of 86% and 67%, respectively. The combination of IL-6 and CRP had a sensitivity of 94%, specificity of 71%, a positive predictive value of 74% and a negative predictive value of 93.75%. CONCLUSIONS Serum IL-6 may be a useful marker for early differentiation of viral and bacterial gastroenteritis in children, especially in combination with CRP.
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Affiliation(s)
- Chien-Hung Lin
- Department of Pediatrics, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, ROC
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Hahn HP, von Specht BU. Secretory delivery of recombinant proteins in attenuated Salmonella strains: potential and limitations of Type I protein transporters. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2003; 37:87-98. [PMID: 12832111 DOI: 10.1016/s0928-8244(03)00092-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Live attenuated Salmonella strains have been extensively explored as oral delivery systems for recombinant vaccine antigens and effector proteins with immunoadjuvant and immunomodulatory potential. The feasibility of this approach was demonstrated in human vaccination trials for various antigens. However, immunization efficiencies with live vaccines are generally significantly lower compared to those monitored in parenteral immunizations with the same vaccine antigen. This is, at least partly, due to the lack of secretory expression systems, enabling large-scale extracellular delivery of vaccine and effector proteins by these strains. Because of their low complexity and the terminal location of the secretion signal in the secreted protein, Type I (ATP-binding cassette) secretion systems appear to be particularly suited for development of such recombinant extracellular expression systems. So far, the Escherichia coli hemolysin system is the only Type I secretion system, which has been adapted to recombinant protein secretion in Salmonella. However, this system has a number of disadvantages, including low secretion capacity, complex genetic regulation, and structural restriction to the secreted protein, which eventually hinder high-level in vivo delivery of recombinant vaccines and effector proteins. Thus, the development of more efficient recombinant protein secretion systems, based on Type I exporters can help to improve efficacies of live recombinant Salmonella vaccines. Type I secretion systems, mediating secretion of bacterial surface layer proteins, such as RsaA in Caulobacter crescentus, are discussed as promising candidates for improved secretory delivery systems.
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Affiliation(s)
- Heinz P Hahn
- Chirurgische Universitätsklinik, Chirurgische Forschung, i. Br., Freiburg, Germany.
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