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1.
Immunol Rev ; 320(1): 100-119, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37694970

RESUMO

Digestive tract cancers (DTC) belong to the most investigated family of tumors. The incidence, prevalence, and mortality rate of DTC remain high, especially for patients with pancreatic cancer. Even though immunotherapy such as immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid cancer types, ICI are still restricted to a very small group of patients and seem to be more efficacious in combination with chemotherapy. Cellular immunotherapy such as CAR T-cell therapy has entered clinical routine in hematological malignancies with outstanding results. There is growing interest on translating this kind of immunotherapy and success into patients with solid malignancies, such as DTC. This review attempts to describe the major advances in preclinical and clinical research with CAR T cells in DTC, considering the most relevant hurdles in each subtype of DTC.


Assuntos
Neoplasias , Neoplasias Pancreáticas , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T , Linfócitos T , Trato Gastrointestinal
2.
Int J Cancer ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150415

RESUMO

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

3.
Gastroenterology ; 165(1): 61-70.e5, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37059339

RESUMO

BACKGROUND & AIMS: Evidence is sparse and inconclusive on the association between long-term fine (≤2.5 µm) particulate matter (PM2.5) exposure and esophageal cancer. We aimed to assess the association of PM2.5 with esophageal cancer risk and compared the esophageal cancer risk attributable to PM2.5 exposure and other established risk factors. METHODS: This study included 510,125 participants without esophageal cancer at baseline from China Kadoorie Biobank. A high-resolution (1 × 1 km) satellite-based model was used to estimate PM2.5 exposure during the study period. Hazard ratios (HR) and 95% CIs of PM2.5 with esophageal cancer incidence were estimated using Cox proportional hazard model. Population attributable fractions for PM2.5 and other established risk factors were estimated. RESULTS: There was a linear concentration-response relationship between long-term PM2.5 exposure and esophageal cancer. For each 10-µg/m3 increase in PM2.5, the HR was 1.16 (95% CI, 1.04-1.30) for esophageal cancer incidence. Compared with the first quarter of PM2.5 exposure, participants in the highest quarter had a 1.32-fold higher risk for esophageal cancer, with an HR of 1.32 (95% CI, 1.01-1.72). The population attributable risk because of annual average PM2.5 concentration ≥35 µg/m3 was 23.3% (95% CI, 6.6%-40.0%), higher than the risks attributable to lifestyle risk factors. CONCLUSIONS: This large prospective cohort study of Chinese adults found that long-term exposure to PM2.5 was associated with an elevated risk of esophageal cancer. With stringent air pollution mitigation measures in China, a large reduction in the esophageal cancer disease burden can be expected.


Assuntos
Neoplasias Esofágicas , Material Particulado , Adulto , Humanos , População do Leste Asiático , Exposição Ambiental/efeitos adversos , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Incidência , Material Particulado/efeitos adversos , Material Particulado/classificação , Estudos Prospectivos , China/epidemiologia , Fatores de Risco
4.
BMC Cancer ; 24(1): 56, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200411

RESUMO

BACKGROUND: The optimal reconstruction method after proximal gastrectomy remains unclear. This systematic review and meta-analysis aimed to compare the short-term outcomes and long-term quality of life of various reconstruction methods. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched to identify comparative studies concerning the reconstruction methods after proximal gastrectomy. The reconstruction methods were classified into six groups: double tract reconstruction (DTR), esophagogastrostomy (EG), gastric tube reconstruction (GT), jejunal interposition (JI), jejunal pouch interposition (JPI) and double flap technique (DFT). Esophagogastric anastomosis group (EG group) included EG, GT and DFT, while esophagojejunal anastomosis group (EJ group) included DTR, JI and JPI. RESULTS: A total of 27 studies with 2410 patients were included in this meta-analysis. The pooled results indicated that the incidences of reflux esophagitis of DTR, EG, GT, JI, JPI and DFT were 7.6%, 27.3%, 4.5%, 7.1%, 14.0%, and 9.1%, respectively. The EG group had more reflux esophagitis (OR = 3.68, 95%CI 2.44-5.57, P < 0.00001) and anastomotic stricture (OR = 1.58, 95%CI 1.02-2.45, P = 0.04) than the EJ group. But the EG group showed shorter operation time (MD=-56.34, 95%CI -76.75- -35.94, P < 0.00001), lesser intraoperative blood loss (MD=-126.52, 95%CI -187.91- -65.12, P < 0.0001) and shorter postoperative hospital stay (MD=-2.07, 95%CI -3.66- -0.48, P = 0.01). Meanwhile, the EG group had fewer postoperative complications (OR = 0.68, 95%CI 0.51-0.90, P = 0.006) and lesser weight loss (MD=-1.25, 95%CI -2.11- -0.39, P = 0.004). For specific reconstruction methods, there were lesser reflux esophagitis (OR = 0.10, 95%CI 0.06-0.18, P < 0.00001) and anastomotic stricture (OR = 0.14, 95%CI 0.06-0.33, P < 0.00001) in DTR than the esophagogastrostomy. DTR and esophagogastrostomy showed no significant difference in anastomotic leakage (OR = 1.01, 95%CI 0.34-3.01, P = 0.98). CONCLUSION: Esophagojejunal anastomosis after proximal gastrectomy can reduce the incidences of reflux esophagitis and anastomotic stricture, while esophagogastric anastomosis has advantages in technical simplicity and long-term weight status. Double tract reconstruction is a safe technique with excellent anti-reflux effectiveness and favorable quality of life. REGISTRATION: This meta-analysis was registered on the PROSPERO (CRD42022381357).


Assuntos
Esofagite Péptica , Qualidade de Vida , Humanos , Constrição Patológica , Gastrectomia/efeitos adversos , Anastomose Cirúrgica/efeitos adversos
5.
Ann Hematol ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382667

RESUMO

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAFV600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up.

6.
Cell Commun Signal ; 22(1): 68, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273295

RESUMO

Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK-STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets. Video Abstract.


Assuntos
Neoplasias Gastrointestinais , Janus Quinases , Humanos , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Microambiente Tumoral
7.
Neuroendocrinology ; 114(2): 120-133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37690447

RESUMO

Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.


Assuntos
Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Carcinoma Neuroendócrino/patologia , Organização Mundial da Saúde , Trato Gastrointestinal/patologia , Neoplasias Pancreáticas/patologia
8.
Pharmacol Res ; 206: 107280, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914382

RESUMO

Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m6A, m1A, m5C, m7G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics.


Assuntos
Epigênese Genética , Humanos , Animais , RNA/genética , RNA/metabolismo , Neoplasias Gastrointestinais/genética , Processamento Pós-Transcricional do RNA , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/terapia
9.
Artigo em Inglês | MEDLINE | ID: mdl-38713196

RESUMO

The genus Exophiala is polymorphic, able to transition between yeast, hyphal and pseudohyphal forms. Species of the genus Exophiala are ubiquitous fungi that are distributed in various environments around the world. During a survey of fungal diversity in the gut of amphipods (Floresorchestia amphawaensis and undescribed Dogielinotid amphipods) from the Amphawa estuary, Samut Songkhram province, Thailand, five black yeast strains (DMKU-MG01, DMKU-MG07, DMKU-MG08, DMKU-HG10 and DMKU-FG04) were identified as representing a novel taxon on the basis of a combination of morphological and molecular phylogenetic features. The five strains did not produce filamentous hyphae or pseudohyphae. Only budding yeast cells were observed. On the basis of the phenotypic characteristics and the results of molecular analyses of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, the five strains were identified as representing a novel species via applied nucleotide pairwise analysis. They differed from the most closely related species Exophiala alcalophiala by 3.54 % nucleotide substitutions (20 nucleotide substitutions in 572 bp) in the D1/D2 domains of the LSU rRNA gene. Moreover, the sequences of the ITS region of the five strains differed from those of the most closely related species E. alcalophiala, by 7.44-9.62 % nucleotide substitutions, and Exophiala halophiala, by 7.2-7.53 % nucleotide substitutions. The results of phylogenetic analyses based on the concatenated sequences of the ITS regions and the D1/D2 domains of the LSU rRNA gene confirmed that the five black yeast strains represented a single novel species of the genus Exophiala. In this study, Exophiala amphawaensis sp. nov. is proposed to accommodate these strains. The holotype is TBRC 15626T and the isotype is PYCC9020. The MycoBank accession number of the novel species is MB 851477.


Assuntos
Anfípodes , DNA Fúngico , DNA Espaçador Ribossômico , Exophiala , Filogenia , Análise de Sequência de DNA , Animais , Tailândia , Anfípodes/microbiologia , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Exophiala/genética , Exophiala/isolamento & purificação , Exophiala/classificação , Técnicas de Tipagem Micológica , Trato Gastrointestinal/microbiologia
10.
BMC Gastroenterol ; 24(1): 304, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251923

RESUMO

BACKGROUND: The association between education, intelligence, and cognition with digestive tract diseases has been established. However, the specific contribution of each factor in the pathogenesis of these diseases are still uncertain. METHOD: This study employed multivariable Mendelian randomization (MR) to assess the independent effects of education, intelligence, and cognition on gastrointestinal conditions in the FinnGen and UK Biobank European-ancestry populations. A two-step MR approach was employed to assess the mediating effects of the association. RESULTS: Meta-analysis of MR estimates from FinnGen and UK Biobank showed that 1- SD (4.2 years) higher education was causally associated with lower risks of gastroesophageal reflux (OR: 0.58; 95% CI: 0.50, 0.66), peptic ulcer (OR: 0.57; 95% CI: 0.47, 0.69), irritable bowel syndrome (OR: 0.70; 95% CI: 0.56, 0.87), diverticular disease (OR: 0.69; 95% CI: 0.61, 0.78), cholelithiasis (OR: 0.68; 95% CI: 0.59, 0.79) and acute pancreatitis (OR: 0.54; 95% CI: 0.41, 0.72), independently of intelligence and cognition. These causal associations were mediating by body mass index (3.7-22.3%), waist-to-hip ratio (8.3-11.9%), body fat percentage (4.1-39.8%), fasting insulin (1.4-5.5%) and major depression (6.0-12.4%). CONCLUSION: Our findings demonstrate a causal and independent association between education and six common digestive tract diseases. Additionally, our study highlights five mediators as crucial targets for preventing digestive tract diseases associated with lower education levels.


Assuntos
Escolaridade , Análise da Randomização Mendeliana , Humanos , Inteligência/genética , Cognição , Doenças do Sistema Digestório/genética , Masculino , Feminino , Pessoa de Meia-Idade , Causalidade , Gastroenteropatias/genética , Fatores de Risco
11.
Support Care Cancer ; 32(8): 501, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985345

RESUMO

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.


Assuntos
Suplementos Nutricionais , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Autoeficácia , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Inquéritos e Questionários , Idoso , Adulto , Neoplasias do Sistema Digestório/cirurgia , Neoplasias do Sistema Digestório/psicologia , Apoio Social , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/psicologia , Período Pós-Operatório
12.
Med Vet Entomol ; 38(3): 366-371, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38741222

RESUMO

Alpha-Gal/α-Gal is an oligosaccharide produced by non-primate mammals. Humans have developed an immune response mediated by anti-α-Gal antibodies that can trigger an allergic reaction and cause anaphylaxis. In recent years, cases of patients with delayed allergic reaction to mammalian meat have been reported worldwide. In Spain, these cases have been related to the species Ixodes ricinus L. (Ixodida: Ixodidae), whose distribution is located in the north of the country. In this work, the presence of α-Gal in water-soluble extracts from samples of salivary glands and digestive tracts of Hyalomma lusitanicum Koch (Ixodida: Ixodidae) both engorged and collected from vegetation were studied. The presence of that epitope was confirmed by the presence of reactive proteins of >250 kDa in both samples. The highest concentrations of α-Gal were detected in salivary glands. Neither sex nor diet influenced the concentration of α-Gal, which seems to indicate its endogenous production and its possible inoculation to the host during tick feeding.


Assuntos
Hipersensibilidade Alimentar , Ixodidae , Animais , Ixodidae/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Masculino , Glândulas Salivares , Espanha , Epitopos , Carne Vermelha/análise , Dissacarídeos/análise
13.
BMC Pediatr ; 24(1): 5, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172693

RESUMO

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.


Assuntos
Corpos Estranhos , Trato Gastrointestinal , Humanos , Criança , Pré-Escolar , Trato Gastrointestinal/cirurgia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Corpos Estranhos/complicações , Vômito/etiologia , Ingestão de Alimentos , Fenômenos Magnéticos
14.
Postgrad Med J ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39362654

RESUMO

PURPOSE: In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs. METHODS: In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds. RESULTS: Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin. CONCLUSION: This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs. Key message What is already known on this topic  The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds  In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy  This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.

15.
Adv Exp Med Biol ; 1446: 15-38, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625523

RESUMO

As for other mammals, the digestive system of dogs (facultative carnivores) and cats (obligate carnivores) includes the mouth, teeth, tongue, pharynx, esophagus, stomach, small intestine, large intestine, and accessory digestive organs (salivary glands, pancreas, liver, and gallbladder). These carnivores have a relatively shorter digestive tract but longer canine teeth, a tighter digitation of molars, and a greater stomach volume than omnivorous mammals such as humans and pigs. Both dogs and cats have no detectable or a very low activity of salivary α-amylase but dogs, unlike cats, possess a relatively high activity of pancreatic α-amylase. Thus, cats select low-starch foods but dogs can consume high-starch diets. In contrast to many mammals, the vitamin B12 (cobalamin)-binding intrinsic factor for the digestion and absorption of vitamin B12 is produced in: (a) dogs primarily by pancreatic ductal cells and to a lesser extent the gastric mucosa; and (b) cats exclusively by the pancreatic tissue. Amino acids (glutamate, glutamine, and aspartate) are the main metabolic fuels in enterocytes of the foregut. The primary function of the small intestine is to digest and absorb dietary nutrients, and its secondary function is to regulate the entry of dietary nutrients into the blood circulation, separate the external from the internal milieu, and perform immune surveillance. The major function of the large intestine is to ferment undigested food (particularly fiber and protein) and to absorb water, short-chain fatty acids (serving as major metabolic fuels for epithelial cells of the large intestine), as well as vitamins. The fermentation products, water, sloughed cells, digestive secretions, and microbes form feces and then pass into the rectum for excretion via the anal canal. The microflora influences colonic absorption and cell metabolism, as well as feces quality. The digestive tract is essential for the health, survival, growth, and development of dogs and cats.


Assuntos
Doenças do Gato , Doenças do Cão , Humanos , Gatos , Cães , Animais , Suínos , Boca , Vitaminas , Mamíferos , Amido , Água
16.
World J Surg Oncol ; 22(1): 73, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38439060

RESUMO

OBJECTIVE: To investigate the clinical efficacy and prognostic implication of hand-sewn anastomosis in laparoscopic total gastrectomy (LTG). METHODS: Retrospective analysis is adopted to the clinicopathologic data of 112 patients with gastric cancer (GC) who went through LTG in the Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University between October 2020 and October 2022. Among them, 60 individuals receiving medical care were split into the hand-sewn anastomosis group (Group H, N = 60); while, 52 individuals were split into the circular stapler anastomosis group (Group C, N = 52) The clinical efficacy and prognostic conditions of hand-sewn anastomosis are compared with those of circular stapler anastomosis in the application of LTG. RESULTS: The analysis results indicated that no notable difference was observed in intraoperative bleeding volume, time to first flatus (TFF), postoperative hospitalization duration and postoperative complications among the two groups (P > 0.05). Group H had shorter esophagojejunal anastomosis duration (20.0 min vs. 35.0 min) and surgery duration (252.6 ± 19.4 min vs. 265.9 ± 19.8 min), smaller incisions (5.0 cm vs. 10.5 cm), and lower hospitalization costs (58415.0 CNY vs. 63382.5 CNY) compared to Group C (P < 0.05). CONCLUSION: The clinical efficacy and the postoperative complications of hand-sewn esophagojejunostomy are basically equivalent in comparison to the circular stapler anastomosis in the application of LTG. Its advantage lies in shorter esophagojejunal anastomosis duration, shorter surgery duration, smaller incisions, lower hospitalization costs and wider adaptability of the location of the tumor.


Assuntos
Gastrectomia , Laparoscopia , Humanos , Estudos Retrospectivos , Gastrectomia/efeitos adversos , Anastomose Cirúrgica , Complicações Pós-Operatórias/etiologia
17.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443193

RESUMO

Drosophila melanogaster females experience a large shift in energy homeostasis after mating to compensate for nutrient investment in egg production. To cope with this change in metabolism, mated females undergo widespread physiological and behavioral changes, including increased food intake and altered digestive processes. The mechanisms by which the female digestive system responds to mating remain poorly characterized. Here, we demonstrate that the seminal fluid protein Sex Peptide (SP) is a key modulator of female post-mating midgut growth and gene expression. SP is both necessary and sufficient to trigger post-mating midgut growth in females under normal nutrient conditions, and likely acting via its receptor, Sex Peptide Receptor (SPR). Moreover, SP is responsible for almost the totality of midgut transcriptomic changes following mating, including up-regulation of protein and lipid metabolism genes and down-regulation of carbohydrate metabolism genes. These changes in metabolism may help supply the female with the nutrients required to sustain egg production. Thus, we report a role for SP in altering female physiology to enhance reproductive output: Namely, SP triggers the switch from virgin to mated midgut state.


Assuntos
Sistema Digestório/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Fertilidade/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores de Peptídeos/metabolismo , Reprodução/fisiologia , Transcriptoma/genética , Animais , Copulação , Sistema Digestório/anatomia & histologia , Sistema Digestório/crescimento & desenvolvimento , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Feminino , Fertilidade/genética , Ontologia Genética , Intestinos/anatomia & histologia , Intestinos/crescimento & desenvolvimento , Intestinos/fisiologia , Masculino , Receptores de Peptídeos/genética , Reprodução/genética , Sêmen/metabolismo , Comportamento Sexual Animal/fisiologia , Transcriptoma/fisiologia
18.
J Clin Nurs ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007189

RESUMO

AIMS: To investigate the incidence of fear of cancer recurrence in patients with digestive tract cancers analyse its influencing factors, and further establish a visual risk prediction model. DESIGN: A cross-sectional study. METHODS: A cross-sectional survey was conducted among 570 patients with digestive tract tumours admitted to a local hospital, from May 2023 to December 2023 by convenient sampling method. Univariate analysis and logistic analysis were performed on the influencing factors, and the risk prediction nomogram model of fear of cancer recurrence in patients with digestive tract cancer was constructed by using R 4.1.3 software. ROC curve was used to evaluate the differentiation of the nomogram model. The calibration curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the consistency of the model. This study was reported using the TRIPOD checklist. RESULTS: In this study, 272 (47.7%) patients developed fear of recurrence. The risk prediction model of recurrence fear column chart for digestive tract cancer patients incorporated six variables of gender, therapy, alimentary tract haemorrhage, pain, depression and social support. The C-statistic was (.976), and the calibration curve showed that the predicted probability was more in line with the actual probability of occurrence, and the decision curve showed that the predictive model had better practicality. CONCLUSION: The column-line diagram prediction model constructed in this study is effective and facilitates timely intervention and management by healthcare professionals based on their risk factors. IMPACT: Nomogram is helpful to calculate the risk probability of FCR in patients with digestive tract cancer, identify FCR patients in time, and formulate comprehensive and personalized countermeasures, to provide a good quality of life and prolong the survival cycle of patients with digestive tract cancer. PATIENT OR PUBLIC CONTRIBUTION: Participants were hospitalized patients or patients with digestive tract cancer undergoing follow-up. First of all, before the investigation and research, a team is formed to discuss the concept, research purpose, method, significance, etc., and determine the research tools. Second, by reasonably explaining the study to patients to seek informed consent from the patient and sign it, patients filled in the questionnaire independently. For patients with low education levels who could not fill in the questionnaire, the team members made objective explanations to help them choose reasonable options.

19.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063090

RESUMO

The urochordate Ciona robusta exhibits numerous functional and morphogenetic traits that are shared with vertebrate models. While prior investigations have identified several analogies between the gastrointestinal tract (i.e., gut) of Ciona and mice, the molecular mechanisms responsible for these similarities remain poorly understood. This study seeks to address this knowledge gap by investigating the transcriptional landscape of the adult stage gut. Through comparative genomics analyses, we identified several evolutionarily conserved components of signaling pathways of pivotal importance for gut development (such as WNT, Notch, and TGFß-BMP) and further evaluated their expression in three distinct sections of the gastrointestinal tract by RNA-seq. Despite the presence of lineage-specific gene gains, losses, and often unclear orthology relationships, the investigated pathways were characterized by well-conserved molecular machinery, with most components being expressed at significant levels throughout the entire intestinal tract of C. robusta. We also showed significant differences in the transcriptional landscape of the stomach and intestinal tract, which were much less pronounced between the proximal and distal portions of the intestine. This study confirms that C. robusta is a reliable model system for comparative studies, supporting the use of ascidians as a model to study gut physiology.


Assuntos
Transdução de Sinais , Animais , Trato Gastrointestinal/metabolismo , Ciona/genética , Ciona/metabolismo , Ciona intestinalis/genética , Ciona intestinalis/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Perfilação da Expressão Gênica
20.
J Fish Biol ; 104(1): 34-43, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37697670

RESUMO

Integrative studies are lacking on the responses of digestive enzymes and energy reserves in conjunction with morphological traits at distinct postprandial times in marine estuarine-dependent flatfishes of ecological and economic importance, such as Paralichthys orbignyanus. We determined total weight (TW), hepato-somatic index (IH), activities of digestive enzymes in the intestine, and the concentration of energy reserves in the liver and the muscle at 0, 24, 72, and 360 h after feeding in juveniles of P. orbignyanus. Amylase activity decreased at 72 h (about 30%). Maltase, sucrose, and lipase activities reached peak at 24 h (67%, 600%, and 35%, respectively). Trypsin and aminopeptidase-N activities at 24 and 72 h, respectively, were lower than those at t = 0 (53% and 30%). A peak increase in the concentration of glycogen and triglycerides in the liver (24 h) (86% and 89%, respectively) occurred. In muscle, glycogen and triglyceride concentrations were unchanged at 24 h and higher at 72 and 360 h (100% and 60%). No changes were found in TW, IH, free glucose in the liver and muscle, and protein in the liver. The protein concentration in the muscle sharply increased at 24 and 360 h after feeding (60%). The results indicate a distinct and specific response of central components of carbohydrate, lipid, and protein metabolism that could be adjustments at the biochemical level upon periods of irregular feeding and even of long-term food deprivation inside coastal lagoons or estuaries. The distinct responses of digestive enzymes in the intestine and energy reserves in the liver and muscle suggest the differential modulation of tissue-specific anabolic and catabolic pathways that would allow the maintenance of physical conditions.


Assuntos
Linguados , Linguado , Animais , Linguados/metabolismo , Proteínas/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Glicogênio/metabolismo , Linguado/metabolismo , Triglicerídeos
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