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Biomolecules Dec 2023Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar... (Review)
Review
Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.
Topics: Animals; Humans; Pancreatitis; Acute Disease; Pancreas; Microbiota; Gastrointestinal Microbiome
PubMed: 38254659
DOI: 10.3390/biom14010059 -
Journal of Leukocyte Biology Nov 2023Monocytes (Mo) and macrophages (Mφ) play important roles in the function of tissues, organs, and systems of all animals during homeostasis, infection, injury, and... (Review)
Review
Monocytes (Mo) and macrophages (Mφ) play important roles in the function of tissues, organs, and systems of all animals during homeostasis, infection, injury, and disease. For decades, conventional wisdom has dictated that Mo and Mφ are end-stage cells that do not proliferate and that Mφ accumulation in tissues is the result of infiltration of Mo from the blood and subsequent differentiation to Mφ. However, reports from the early 1900s to the present describe evidence of Mo and Mφ proliferation in different tissues and contexts. The purpose of this review is to summarize both historical and current evidence for the contribution of Mφ proliferation to their accumulation in different tissues during homeostasis, infection, injury, and disease. Mφ proliferate in different organs and tissues, including skin, peritoneum, lung, heart, aorta, kidney, liver, pancreas, brain, spinal cord, eye, adipose tissue, and uterus, and in different species including mouse, rat, rabbit, and human. Mφ can proliferate at different stages of differentiation with infiltrating Mo-like cells proliferating in certain inflammatory contexts (e.g. skin wounding, kidney injury, bladder and liver infection) and mature resident Mφ proliferating in other inflammatory contexts (e.g. nematode infection, acetaminophen liver injury) and during homeostasis. The pathways involved in stimulating Mφ proliferation also may be context dependent, with different cytokines and transcription factors implicated in different studies. Although Mφ are known to proliferate in health, injury, and disease, much remains to be learned about the regulation of Mφ proliferation in different contexts and its impact on the homeostasis, injury, and repair of different organs and tissues.
Topics: Humans; Female; Mice; Rats; Animals; Rabbits; Monocytes; Macrophages; Cytokines; Homeostasis; Cell Proliferation
PubMed: 37555460
DOI: 10.1093/jleuko/qiad093 -
Best Practice & Research. Clinical... Jul 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs,... (Review)
Review
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs, such as the pancreas, adrenal, thyroid, and adipose tissue. The main receptor for SARS-CoV-2, ACE2, is ubiquitously expressed in the cells of the endocrine organs and accordingly, the virus has been detected in various amounts in all endocrine tissues in post-mortem samples from COVID-19 patients. The infection with SARS-CoV-2 may directly lead to organ damage or dysfunction, such as hyperglycaemia or in rare cases, new-onset diabetes. Furthermore, an infection with SARS-CoV-2 may have indirect effects affecting the endocrine system. The exact mechanisms are not yet completely understood and have to be further investigated. Conversely, endocrine diseases may affect the severity of COVID-19 and emphasis has to be laid on reducing the prevalence, or enhance the treatment, of these often non-communicable diseases in the future.
Topics: Humans; COVID-19; SARS-CoV-2; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme 2; Endocrine Glands
PubMed: 36907787
DOI: 10.1016/j.beem.2023.101761 -
Molecular Cancer Sep 2023Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC...
Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.
Topics: Humans; Proteomics; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Genomics; Adenocarcinoma; Stomach Neoplasms
PubMed: 37674200
DOI: 10.1186/s12943-023-01796-w -
Diabetologia Jul 2023'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This... (Review)
Review
'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This review focuses on 'starting the clock', i.e. the initiation of pre-symptomatic islet autoimmunity/the first appearance of islet autoantibodies. In particular, this review addresses why susceptibility to developing islet autoimmunity is greatest in the first 2 years of life and why beta cells are a frequent target of the immune system during this fertile period. A concept for the development of beta cell autoimmunity in childhood is discussed and three factors are highlighted that contribute to this early predisposition: (1) high beta cell activity and potential vulnerability to stress; (2) high rates of and first exposures to infection; and (3) a heightened immune response, with a propensity for T helper type 1 (Th1) immunity. Arguments are presented that beta cell injury, accompanied by activation of an inflammatory immune response, precedes the initiation of autoimmunity. Finally, the implications for strategies aimed at primary prevention for a world without type 1 diabetes are discussed.
Topics: Female; Humans; Diabetes Mellitus, Type 1; Islets of Langerhans; Autoimmunity; Autoantibodies; Insulin-Secreting Cells; Genetic Predisposition to Disease
PubMed: 37231274
DOI: 10.1007/s00125-023-05927-2 -
Frontiers in Endocrinology 2023Coronavirus disease 2019 (COVID-19) caused a major pandemic affecting human health and economy around the world since the beginning of 2020. The virus responsible for... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused a major pandemic affecting human health and economy around the world since the beginning of 2020. The virus responsible for the disease is "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It invades the target cells by binding to angiotensin-converting enzyme 2 (ACE2). ACE2 is expressed in several organs including endocrine glands. Multiple endocrine and metabolic systems including the endocrine pancreas have been impacted by COVID-19 infection/pandemic. COVID-19 pandemic can promote obesity through alterations in lifestyle (e.g., unhealthy diet and reduced physical activity due to confinement and isolation) leading to type 2 diabetes and/or can directly impair the function of the endocrine pancreas particularly through a cytokine storm, promoting or aggravating type 1 or type 2 diabetes. The increased ACE2 receptors of high adiposity commonly associated with type 2 diabetes and the chronic hyperglycemia of diabetes with its negative impact on the immune system can increase the risk of COVID-19 infection and its morbidity/mortality. In conclusion, there are bidirectional interactions between COVID-19 pandemic and diabetes (e.g., COVID-19 infection can impact diabetes and diabetes can impact COVID-19 infection). The services offered by healthcare systems for the management of diabetes have been adapted accordingly.
Topics: Humans; COVID-19; SARS-CoV-2; Renin-Angiotensin System; Angiotensin-Converting Enzyme 2; Peptidyl-Dipeptidase A; Diabetes Mellitus, Type 2; Pandemics
PubMed: 38292772
DOI: 10.3389/fendo.2023.1306290 -
The Journal of Clinical Endocrinology... Aug 2023Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity....
Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the COVID-19 pandemic, cases of hyperglycemia, diabetic ketoacidosis, and new diabetes increased, suggesting that SARS-CoV-2 may be a trigger for or unmask T1D. Possible mechanisms of β-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic β cells, and damage to β cells because of infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet β cells in these 3 aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry, and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.
Topics: Humans; COVID-19; Diabetes Mellitus, Type 1; SARS-CoV-2; Pandemics; Islets of Langerhans
PubMed: 36950864
DOI: 10.1210/clinem/dgad165 -
Maedica Dec 2023Duodenopancreatectomy is a surgical procedure that involves the removal of part of the pancreas, duodenum, and bile ducts. This procedure is commonly performed in...
Duodenopancreatectomy is a surgical procedure that involves the removal of part of the pancreas, duodenum, and bile ducts. This procedure is commonly performed in patients with pancreatic cancer or other gastrointestinal disorders. However, the safety and efficacy of duodenopancreatectomy in older adults (octogenarians) remain unclear. The goal of this review is to assess the outcomes and complications of duodenopancreatectomy in octogenarian patients. A systematic search of relevant literature was conducted using PubMed, Embase and the Cochrane Library databases. Studies reporting the outcomes and complications of duodenopancreatectomy in octogenarian patients were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Egger's test was used to evaluate publication bias. A total of 14 studies were included in this review. The outcomes of duodenopancreatectomy in octogenarian patients were generally favorable, with a median 30-day mortality rate of 3.5% (range 0-16.7%). The most common complications were pancreatic fistula (12.2%), delayed gastric emptying (6.3%) and wound infection (5.5%). The overall long-term survival rate of octogenarian patients after duodenopancreatectomy was 21.2%. Duodenopancreatectomy can be safely performed in carefully selected octogenarian patients with good outcomes. However, this procedure is associated with a high risk of complications, particularly pancreatic fistula, in this age group.
PubMed: 38348067
DOI: 10.26574/maedica.2023.18.4.705