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1.
Cancer Control ; 31: 10732748241278921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39222361

RESUMO

OBJECTIVE: This study was conducted to investigate the imaging information, laboratory data, and clinical characteristics of duodenal papillary malignancies, aiming to contribute to the early diagnosis of these diseases. METHODS: The clinical characteristics, laboratory data, and computed tomography (CT) findings of 17 patients with adenoma of the major duodenal papilla (the adenoma group) and 58 patients with cancer of the major duodenal papilla (the cancer group) were retrospectively analyzed. The measurement data were analyzed using t test and expressed as mean ± standard deviation. The counting data were analyzed using the χ2 test and expressed in n (%). Pearson correlation analysis was also conducted, and a scatter plot was drawn. RESULTS: There were significant differences in the diameter, shape, margin, and target sign of the major duodenal papilla, pancreatic duct diameter, common bile duct diameter, enhancement uniformity, fever, direct bilirubin, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9, and jaundice between the adenoma group and the cancer group (P < .01). The enhancement magnitude of the duodenal papilla was correlated with the lesion size, and the venous phase CT value of the enhanced scan was correlated with the duodenal papilla diameter (P < .05). Additionally, 12 patients in the cancer group suffered from malignant transformation of adenomas. CONCLUSION: Firstly, CT is of high value in the diagnosis of duodenal papilla diseases. Secondly, the enhancement magnitude of the duodenal papilla is correlated with the lesion size. Thirdly, patients with duodenal papilla adenomas have a risk of progression into adenocarcinoma, thereby requiring close follow-up.


Assuntos
Neoplasias Duodenais , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/sangue , Neoplasias Duodenais/patologia , Idoso , Adulto , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Adenoma/sangue , Adenoma/patologia
2.
Microb Pathog ; 167: 105572, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35561978

RESUMO

The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection.


Assuntos
Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Ictaluridae , Acroleína/análogos & derivados , Aeromonas hydrophila , Animais , Doenças dos Peixes/microbiologia , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/veterinária
3.
Virol J ; 19(1): 133, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945590

RESUMO

The clinical data of a patient with Epstein-barr virus (EBV) associated with cholangiocarcinoma was reported in this paper: a case of a 36-year-old female presented with abdominal pain and systemic skin yellowing combined with skin itching. Laboratory studies showed increase in alanine aminotransferase 242 U/L, aspartate aminotransferase 404 U/L, r-glutamyltransferase 1516 U/L, total bilirubin 308.2 µmol/L and CA199 (101.0 U/ml). AFP (4.5 ng/ml) was normal. CT revealed multiple space-occupying lesions in the liver. PET-CT revealed liver malignant tumor and lymph node metastasis. Liver puncture pathology revealed infiltrative growth of significant heterocyst nests in the liver tissue, which was morphologically consistent with malignant tumors, considering poorly differentiated carcinoma. Pathology suggestion: combining liver puncture with morphology, immunohistochemistry, and EBV in situ hybridization results, it was consistent with EB virus-associated poorly differentiated carcinoma, therefore, consider EBV infection-associated poorly differentiated cholangiocarcinoma (CCA) (LELC morphology). The patient underwent liver transplantation in Hangzhou Shulan Hospital on June 8, 2021 successfully. After surgery, the patient orally took tacrolimus for anti-rejection, entecavir for antiviral therapy, gemcitabine 1.2 g + cis-platinum 30 mg for chemotherapy. After following up for more than 5 months post liver transplantation, the condition of the patient deteriorated. The patient subsequently died. Based on the case of our patient and the review of existing literature, when the patient's serum CA199 increased, AFP did not change significantly, and there was no previous history of hepatitis B. CT revealed a low-density mass in the liver, ring enhancement in the arterial phase, and heterogeneous enhancement of the tumor in the delayed phase. Ring enhancement of the liver lesion mass was observed on MRI. Consider the might possibility of hepatic CCA. When patients showed recurrent tonsillitis at an early age, EBV virus infection should be vigilant and oropharyngeal tissue should persist, diagnosis of EBV-associated liver cancer should be considered. In particular, EBV infection-related liver cancer is relatively rare, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Hepáticas , Adulto , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Herpesvirus Humano 4/genética , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , alfa-Fetoproteínas
4.
Int Microbiol ; 25(3): 605-613, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35438439

RESUMO

Aeromonas hydrophila is a common pathogen in fish that has caused severe economic losses in aquaculture worldwide. With the emergence of bacterial resistance, it is necessary to develop new drugs to combat bacterial infection, particularly for multidrug-resistant bacteria. In this study, the antibacterial activity of pinocembrin was investigated by observing bacterial growth and microscopic structure, and its mechanism of action was identified by investigating its effect on protein and DNA. The antibacterial susceptibility test indicated that pinocembrin inhibits A. hydrophila growth. The minimal inhibitory concentration and minimum bactericidal concentration were 256 µg/mL and 512 µg/mL, respectively. Ultrastructurally, the bacteria treated with pinocembrin showed surface roughness and plasmolysis. When bacteria were treated with 512 µg/mL pinocembrin, lactate dehydrogenase activity and soluble protein content decreased significantly, and electrical conductivity and DNA exosmosis levels increased by 4.21 ± 0.64% and 15.98 ± 1.93 mg/L, respectively. Staining with 4', 6-Diamidino-2-phenylindole showed that the nucleic acid fluorescence intensity and density decreased after the treatment with pinocembrin. Pinocembrin may inhibit the growth of A. hydrophila by increasing cell membrane permeability and affecting protein and DNA metabolism. Thus, pinocembrin is a candidate drug for the treatment of A. hydrophila infection in aquaculture.


Assuntos
Doenças dos Peixes , Flavanonas , Aeromonas hydrophila , Animais , Antibacterianos/química , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Testes de Sensibilidade Microbiana
5.
Pharmacol Res ; 165: 105469, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33524541

RESUMO

The communication between neurons constitutes the basis of all neural activities, and synaptic vesicle exocytosis is the fundamental biological event that mediates most communication between neurons in the central nervous system. The SNARE complex is the core component of the protein machinery that facilitates the fusion of synaptic vesicles with presynaptic terminals and thereby the release of neurotransmitters. In synapses, each release event is dependent on the assembly of the SNARE complex. In recent years, basic research on the SNARE complex has provided a clearer understanding of the mechanism underlying the formation of the SNARE complex and its role in vesicle formation. Emerging evidence indicates that abnormal expression or dysfunction of the SNARE complex in synapse physiology might contribute to abnormal neurotransmission and ultimately to synaptic dysfunction. Clinical research using postmortem tissues suggests that SNARE complex dysfunction is correlated with various neurological diseases, and some basic research has also confirmed the important role of the SNARE complex in the pathology of these diseases. Genetic and pharmacogenetic studies suggest that the SNARE complex and individual proteins might represent important molecular targets in neurological disease. In this review, we summarize the recent progress toward understanding the SNARE complex in regulating membrane fusion events and provide an update of the recent discoveries from clinical and basic research on the SNARE complex in neurodegenerative, neuropsychiatric, and neurodevelopmental diseases.


Assuntos
Transtornos Mentais/metabolismo , Doenças do Sistema Nervoso/metabolismo , Proteínas SNARE/metabolismo , Vesículas Sinápticas/metabolismo , Animais , Exocitose/fisiologia , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/genética , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Proteínas SNARE/genética , Vesículas Sinápticas/genética , Vesículas Sinápticas/patologia
6.
Fish Shellfish Immunol ; 99: 424-434, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32087278

RESUMO

Virulent pathogenic microorganisms often enhance their infectivity through immune evasion mechanisms. Our research on the integrative and conjugative element (ICE(r2)) of the virulent fish pathogen Yersinia ruckeri SC09 led to the identification of genes related to immune evasion (designated stir-1, stir-2, stir-3 and stir-4), among which stir-1 and stir-2 were determined as the key contributors to bacterial toxicity and immune evasion. Here, we further examined the ability of stir-3 to mediate immune evasion based on detailed bioinformatic analysis of ICE(r2) from Y. ruckeri SC09. Interactions among the translated STIR-1, STIR-2, STIR-3 and STIR-4 proteins in the secretory process were additionally explored. STIR-3 was positively correlated with bacterial toxicity and inhibited host toll-like receptor (TLR) signaling by interacting with MyD88, thereby facilitating bacterial survival in host cells. Importantly, our data showed co-secretion of STIR-1, STIR-2 and STIR-3 as a complex, with secretion failure occurring in the absence of any one of these proteins. While stir-1, stir-2, stir-3 and stir-4 genes werespecific to Y. ruckeri SC09, the ICE(r2) region where these genes were located is a mobile component widely distributed in bacteria. Therefore, the potential transmission risk of these immune evasion genes requires further research attention.


Assuntos
Proteínas de Bactérias/genética , Oncorhynchus mykiss/microbiologia , Transdução de Sinais/imunologia , Fatores de Virulência/genética , Yersiniose/veterinária , Animais , Proteínas de Bactérias/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Imunidade Inata , Fator 88 de Diferenciação Mieloide/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia , Fatores de Virulência/imunologia , Yersiniose/imunologia , Yersinia ruckeri/imunologia , Yersinia ruckeri/patogenicidade
7.
Fish Shellfish Immunol ; 103: 357-365, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32461169

RESUMO

Immune escape is a common feature of bacteria, viruses, parasites and even cancer cells. Our earlier work on an integrative and conjugative element (ICEr2) of Yersinia ruckeri SC09 demonstrated contributory roles of stir-1, stir-2 and stir-3 in bacterial toxicity and ability to code for immune evasion. Here, we further examined the ability of stir-4 in ICE (r2) and its encoded STIR-4 protein to mediate immune evasion using comparative genomic analysis. Additionally, the mechanisms underlying the synergistic activities of STIR-1, STIR-2, STIR-3 and STIR-4 in immune evasion were examined. Our results showed that STIR-4 did not contribute to bacterial toxicity, either in vivo nor in vitro, or show the ability to assist in bacterial immune escape. STIR-1, STIR-2, and STIR-3 formed heterotrimers in bacteria while facilitating immune evasion, which we speculate may be essential to maintain their stability. This discovery also partially explains the previous finding that a single gene can mediate immune evasion. Our data provide further knowledge on the distribution of ICE (r2)-like elements in bacteria, validating the prevalence of large-scale gene transfer in pathogens and its potential for enhancing virulence levels. Further studies are necessary to establish the biological significance of the ICE (r2) component.


Assuntos
Proteínas de Bactérias/genética , Doenças dos Peixes/imunologia , Evasão da Resposta Imune/genética , Oncorhynchus mykiss , Yersiniose/veterinária , Yersinia ruckeri/fisiologia , Animais , Proteínas de Bactérias/imunologia , Transdução de Sinais , Yersiniose/imunologia
8.
Fish Shellfish Immunol ; 94: 58-65, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31470137

RESUMO

TIR domain-containing protein is an important member for some bacterial pathogens to subvert host defenses. Here we described a fish virulent Yersinia ruckeri SC09 strain that interfered directly with Toll-like receptor (TLR) function by a TIR-containing protein. Firstly, the novel TIR-containing protein was identified by bioinformatics analysis and named as TcpA. Secondly, the toxic effects of TcpA in fish was demonstrated in vivo challenge experiments through knockout mutant and complement mutant of tcpA gene. Thirdly, The study in vitro revealed that TcpA could down-regulate the expression and secretion of IL-6, IL-1ß and TNF-α. Finally, we demonstrated that TcpA could inhibit the TLR signaling pathway through interaction with myeloid differentiation factor 88 (MyD88) in experiments such as NF-κB dependent luciferase reporter system, co-immunoprecipitation, GST pull-down and yeast two-hybrid. The study revealed that TcpA was essential for virulence and was able to interact with the TIR adaptor protein MyD88 and inhibit the pre-inflammatory signal of immune cells and promote the intracellular survival of pathogenic Yersinia ruckeri SC09 strain. In conclusion, our results showed that TcpA acted as a new virulence factor in Y. ruckeri could suppress innate immune response and increase virulence by inhibiting TLR and MyD88-mediated specific signaling, highlighting a novel strategy for innate immune evasion in bacteria.


Assuntos
Evasão da Resposta Imune/genética , Imunidade Inata/genética , Fator 88 de Diferenciação Mieloide/genética , Receptores Toll-Like/genética , Fatores de Virulência/genética , Yersiniose/veterinária , Yersinia ruckeri/genética , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Doenças dos Peixes/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/metabolismo , Fatores de Virulência/metabolismo , Yersiniose/genética , Yersiniose/imunologia
9.
Int J Mol Sci ; 20(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500298

RESUMO

TIR domain-containing proteins are essential for bacterial pathogens to subvert host defenses. This study describes a fish pathogen, Yersinia ruckeri SC09 strain, with a novel TIR domain-containing protein (STIR-2) that affects Toll-like receptor (TLR) function. STIR-2 was identified in Y. ruckeri by bioinformatics analysis. The toxic effects of this gene on fish were determined by in vivo challenge experiments in knockout mutants and complement mutants of the stir-2 gene. In vitro, STIR-2 downregulated the expression and secretion of IL-6, IL-1ß, and TNF-α. Furthermore, the results of NF-κB-dependent luciferase reporter system, co-immunoprecipitation, GST pull-down assays, and yeast two-hybrid assay indicated that STIR-2 inhibited the TLR signaling pathway by interacting with myeloid differentiation factor 88 (MyD88). In addition, STIR-2 promoted the intracellular survival of pathogenic Yersinia ruckeri SC09 strain by binding to the TIR adaptor protein MyD88 and inhibiting the pre-inflammatory signal of immune cells. These results showed that STIR-2 increased virulence in Y. ruckeri and suppressed the innate immune response by inhibiting TLR and MyD88-mediated signaling, serving as a novel strategy for innate immune evasion.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Doenças dos Peixes/microbiologia , Fator 88 de Diferenciação Mieloide/metabolismo , Yersiniose/veterinária , Yersinia ruckeri/patogenicidade , Proteínas Adaptadoras de Transporte Vesicular/imunologia , Animais , Aderência Bacteriana , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Evasão da Resposta Imune , Camundongos Knockout , Oncorhynchus mykiss , Domínios Proteicos , Transdução de Sinais , Receptores Toll-Like/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/imunologia , Yersiniose/imunologia , Yersinia ruckeri/genética , Yersinia ruckeri/imunologia
10.
J Alzheimers Dis ; 101(2): 379-396, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39213063

RESUMO

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and is characterized by a decrease in learning capacity, memory loss and behavioral changes. In addition to the well-recognized amyloid-ß cascade hypothesis and hyperphosphorylated Tau hypothesis, accumulating evidence has led to the proposal of the mitochondrial dysfunction hypothesis as the primary etiology of AD. However, the predominant molecular mechanisms underlying the development and progression of AD have not been fully elucidated. Mitochondrial dysfunction is not only considered an early event in AD pathogenesis but is also involved in the whole course of the disease, with numerous pathophysiological processes, including disordered energy metabolism, Ca2+ homeostasis dysfunction and hyperactive oxidative stress. In the current review, we have integrated emerging evidence to summarize the main mitochondrial alterations- bioenergetic metabolism, mitochondrial inheritance, mitobiogenesis, fission- fusion dynamics, mitochondrial degradation, and mitochondrial movement- underlying AD pathogenesis; precisely identified the mitochondrial regulators; discussed the potential mechanisms and primary processes; highlighted the leading players; and noted additional incidental signaling pathway changes. This review may help to stimulate research exploring mitochondrial metabolically-oriented neuroprotection strategies in AD therapies, leading to a better understanding of the link between the mitochondrial dysfunction hypothesis and AD pathogenesis.


Assuntos
Doença de Alzheimer , Mitocôndrias , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Animais , Dinâmica Mitocondrial/fisiologia , Estresse Oxidativo/fisiologia , Metabolismo Energético/fisiologia
11.
Int J Biol Macromol ; 273(Pt 1): 132872, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38942671

RESUMO

Diseases caused by viruses pose a significant risk to the health of aquatic animals, for which there are presently no efficacious remedies. Interferon (IFN) serving as an antiviral agent, is frequently employed in clinical settings. Due to the unique living conditions of aquatic animals, traditional injection of interferon is cumbersome, time-consuming and labor-intensive. This study aimed to prepare IFN microcapsules through emulsion technique by using resistant starch (RS) and carboxymethyl chitosan (CMCS). Optimization was achieved using the Box-Behnken design (BBD) response surface technique, followed by the creation of microcapsules through emulsification. With RS at a concentration of 1.27 %, a water­oxygen ratio of 3.3:7.4, CaCl2 at 13.67 %, CMCS at 1.04 %, the rate of encapsulation can escalate to 80.92 %. Rainbow trout infected with Infectious hematopoietic necrosis virus (IHNV) and common carp infected with Spring vireemia (SVCV) exhibited a relative survival rate (RPS) of 65 % and 60 % after treated with IFN microcapsules, respectively. Moreover, the microcapsules effectively reduced the serum AST levels and enhanced the expression of IFNα, IRF3, ISG15, MX1, PKR and Viperin in IHNV-infected rainbow trout and SVCV-infected carp. In conclusion, this integrated IFN microcapsule showed potential as an antiviral agent for treatment of viral diseases in aquaculture.


Assuntos
Interferon-alfa , Oncorhynchus mykiss , Proteínas Recombinantes , Animais , Oncorhynchus mykiss/virologia , Interferon-alfa/farmacologia , Proteínas Recombinantes/farmacologia , Cápsulas , Antivirais/farmacologia , Antivirais/química , Composição de Medicamentos , Quitosana/química , Quitosana/análogos & derivados , Vírus da Necrose Hematopoética Infecciosa/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Doenças dos Peixes/virologia , Doenças dos Peixes/tratamento farmacológico
12.
Int J Immunopathol Pharmacol ; 37: 3946320231157868, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36762724

RESUMO

Objective: To investigate the computed tomography (CT) findings of chronic duodenal papilla mucositis and duodenal papillary carcinoma, and provide more imaging information for early diagnosis of duodenal malignant diseases.Methods: CT findings and clinical data of 40 patients with chronic duodenal papilla mucositis and 46 patients with duodenal papillary carcinoma were retrospectively analyzed. Observation and measuring of direct duodenal papilla signs (including size, shape, density, enhancement uniformity, etc.), indirect duodenal papilla signs (including pancreaticobiliary dilatation) and clinical indicators (including tumor markers CA19-9, CA125, CEA, blood routine white blood cell count, bilirubin, age, gender, etc.) were carried out according to CT as well as statistical analysis.Results: There were significant differences in duodenal papilla regular morphology, age and CA19-9 (p < .05), and significant differences in duodenal papilla maximum transverse diameter, diameter of common bile duct, diameter of pancreatic duct, total bilirubin, direct bilirubin, and jaundice in duodenal papillary carcinoma group (p < 0.01). There were no significant differences in duodenal papilla enhancement uniformity, plain CT value, arterial CT value, portal CT value, enhancement uniformity, presence or not of calculus at the lower end, gender, CEA, CA125, white blood cell count, and abdominal pain with fever (all p > .05).Conclusion: CT is helpful for the diagnosis of duodenal papilla disease, but the CT findings of patients with duodenal papillary carcinoma tend to be similar to findings of chronic duodenal papilla mucositis, which is easy to lead to misdiagnosis, so comprehensive diagnosis should be made according to the direct and indirect CT signs as well as laboratory and clinical manifestations of duodenal papilla, so as to improve the diagnosis of duodenal papillary carcinoma, and reduce missed diagnosis and misdiagnosis.


Assuntos
Carcinoma Papilar , Neoplasias Duodenais , Mucosite , Humanos , Antígeno CA-19-9 , Estudos Retrospectivos , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Tomografia Computadorizada por Raios X/métodos , Bilirrubina
13.
Mol Ther Nucleic Acids ; 33: 529-542, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37588688

RESUMO

Apolipoprotein E (ApoE) is a multifunctional protein critical for lipid metabolism and cholesterol homeostasis. In addition to being a well known genetic determinant of both neurodegenerative and cardiovascular diseases, ApoE is frequently involved in various viral infection-related diseases. Human ApoE protein is functionally polymorphic with three isoforms, namely, ApoE2, ApoE3, and ApoE4, with markedly altered protein structures and functions. ApoE4 is associated with increased susceptibility to infection with herpes simplex virus type-1 and HIV. Conversely, ApoE4 protects against hepatitis C virus and hepatitis B virus infection. With the outbreak of coronavirus disease 2019, ApoE4 has been shown to determine the incidence and progression of severe acute respiratory syndrome coronavirus 2 infection. These findings clearly indicate the critical role of ApoE in viral infection. Furthermore, ApoE polymorphism has various or even opposite effects in these infection processes, which are partly related to the structural features that distinguish the different ApoE statuses. In the current review, we summarize the emerging relationship between ApoE and viral infection, discuss the potential mechanisms, and identify future directions that may help to advance our understanding of the link between ApoE and viral infection.

14.
Front Aging Neurosci ; 15: 1258640, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020775

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aß), hyperphosphorylation of tau, and neuroinflammation in the brain. The blood-brain barrier (BBB) limits solutes from circulating blood from entering the brain, which is essential for neuronal functioning. Focusing on BBB function is important for the early detection of AD and in-depth study of AD pathogenic mechanisms. However, the mechanism of BBB alteration in AD is still unclear, which hinders further research on therapeutics that target the BBB to delay the progression of AD. The exact timing of the vascular abnormalities in AD and the complex cause-and-effect relationships remain uncertain. Thus, it is necessary to summarize and emphasize this process. First, in this review, the current evidence for BBB dysfunction in AD is summarized. Then, the interrelationships and pathogenic mechanisms between BBB dysfunction and the risk factors for AD, such as Aß, tau, neuroinflammation, apolipoprotein E (ApoE) genotype and aging, were analyzed. Finally, we discuss the current status and future directions of therapeutic AD strategies targeting the BBB. We hope that these summaries or reviews will allow readers to better understand the relationship between the BBB and AD.

15.
J Thorac Dis ; 15(2): 529-541, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36910081

RESUMO

Background: Serum miR-186-5p levels are increased in acute myocardial infarction (AMI) patients and might contribute to assessing the prognosis of AMI patients. In this study, we further investigated the underlying molecular mechanism of miR-186-5p that participated in the pathological processes of myocardial ischemia. Methods: The AMI models of rats and oxygen-glucose deprivation (OGD) models of H9c2 cells were established. Bioinformatics databases, luciferase reporting, and western blotting assays were performed to identify the regulatory target of miR-186-5p. Transfection and functional experiments were conducted to further define the possible molecular mechanism of miR-186-5p during the process of glucose deficiency and hypoxia. Results: The level of miR-186-5p was found to significantly decrease in H9c2 cells after OGD treatment, while it increased in the culture medium from OGD-treated H9c2 cells. Using bioinformatics databases, luciferase reporting, and western blotting assays, we identified that ERK1/2 might serve as the negative regulatory target of miR-186-5p. Combined with further transfection experiments, we indicated that miR-186-5p might inhibit the expression and activation of ERK1/2. This finding was also reflected in the reduction of their downstream cleaved caspase-3. Through functional experiments, we revealed that miR-186-5p might inhibit apoptosis and promote proliferation in OGD-treated H9c2 cells. Conclusions: We demonstrated that miR-186-5p might suppress OGD-induced apoptosis in H9c2 cells by targeting the ERK1/2 pathway.

16.
Microorganisms ; 11(11)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38004823

RESUMO

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host's immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance.

17.
Anim Reprod Sci ; 255: 107294, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37421833

RESUMO

The environment encountered by the fetus during its development exerts a profound influence on its physiological function and disease risk in adulthood. Women's intake of high-fat diet during pregnancy and lactation has gradually become an issue of widespread concern. Maternal high-fat diet will not only cause abnormal neurological development and metabolic syndrome symptoms in the offspring, but also affect the fertility of female offspring. Maternal high-fat diet affects the expression of genes related to follicle growth in offspring, such as AAT, AFP and GDF-9, which reduces the number of follicles and impairs follicle development. Additionally, maternal high-fat diet also affects ovarian health by inducing ovarian oxidative stress and cell apoptosis, which collectively can impair the reproductive potential of female offspring. Reproductive potential carries significant importance for both humans and animals. Therefore, this review aims to describe the effect of maternal exposure to high-fat diet on the ovarian development of offspring and to discuss possible mechanisms by which maternal diet affects the growth and metabolism of offspring.


Assuntos
Dieta Hiperlipídica , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Animais , Humanos , Dieta Hiperlipídica/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/veterinária , Reprodução , Ovário/metabolismo , Folículo Ovariano , Lactação/fisiologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia
18.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37330668

RESUMO

This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landrace × Large White, parity: 3.93 ±â€…0.11) were allocated to three dietary treatments (n = 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (P < 0.01, P = 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (P < 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (P < 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (P < 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (P < 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (P = 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (P = 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (P < 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (P = 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (P < 0.05). YDP supplementation increased the IgA content in the milk (P < 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (P = 0.05); and the content of transforming growth factor-ß in the YDP group was higher than that in the CON group (P < 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (P < 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.


Rapid fetal and reproductive tissue development in late gestation poses a challenge to sow health. Nutritional interventions have been shown to effectively improve animal performance. The present study investigated whether dietary supplementation with a yeast-derived postbiotic (YDP) during late gestation and lactation might improve the health and production performance of sows and piglets. At two tested dose levels (1.25 and 2.00 g/kg in the diet), dietary YDP supplementation increased backfat deposition in sows during late gestation and weaning weight in piglets, and decreased the diarrhea index in piglets. YDP supplementation tended to increase lactose content in sow milk. Dietary YDP supplementation improved immunity in sows at farrowing and piglets at weaning. These findings indicated that YDP use improves sows' production performance and may serve as an important approach to optimizing nutrient programs in sow production.


Assuntos
Lactação , Leite , Animais , Gravidez , Suínos , Feminino , Saccharomyces cerevisiae , Colostro , Lactose , Dieta/veterinária , Suplementos Nutricionais , Paridade , Imunoglobulina A , Imunoglobulina G , Imunoglobulina A Secretora/farmacologia , Diarreia/veterinária , Imunidade , Ração Animal/análise
19.
Microorganisms ; 11(9)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37764136

RESUMO

Dietary fiber is a substance that cannot be digested by endogenous digestive enzymes but can be digested by the cellulolytic enzymes produced by intestinal microorganisms. In the past, dietary fiber was considered an anti-nutrient component in diets because it could resist digestion by endogenous enzymes secreted by the intestine and has a negative effect on the digestion of energy-producing nutrients. However, due to its functional properties, potential health benefits to animals, and innate fermentability, it has attracted increasing attention in recent years. There are a plethora of studies on dietary fiber. Evidence suggests that dietary fiber can provide energy for pigs through intestinal microbial fermentation and improve sow welfare, reproductive performance, intestinal flora, and immunity. This is a brief overview of the composition and classification of dietary fiber, the mechanism of action and effects of dietary fiber on reproductive performance, intestinal microorganisms, and the immune index of the sow. This review also provides scientific guidance for the application of dietary fiber in sow production.

20.
Transl Neurosci ; 13(1): 93-103, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35582645

RESUMO

Alzheimer's disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E (ApoE) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE. Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE-TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.

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