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1.
Zhonghua Yi Xue Za Zhi ; 101(34): 2703-2709, 2021 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-34510877

RESUMO

Objective: To investigate the value of spleen density in predicting the prognosis of patients with gastric cancer after radical gastrectomy. Methods: A total of 415 patients with gastric cancer who underwent radical resection in the Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from January 2012 to December 2015 were retrospectively analyzed. Of the patients, there were 295 males and 120 femles with a median age of 59 years (range 28-83 years). The patients were divided into diffuse decreased spleen density group (DROSD) (spleen density≤43.0 HU, n=118) and non-diffuse decreased spleen density group (N-DROSD) (spleen density>43.0 HU, n=297) according to the density of spleen detected by computed tomography (CT). The receiver operating characteristic (ROC) curve was used to identify the checkpoint of spleen density in predicting the recurrence of the gastric cancer in those patients. The relationship with clinicopathological factors and prognosis in the two groups were further analyzed. Results: The optimal critical value of spleen density for predicting postoperative recurrence of gastric cancer was 43.0 HU, the area under the curve of ROC was 0.608, and the sensitivity and specificity was 84.9% and 40.4%, respectively. Spleen density was related to albumin, hemoglobin, neutrophil lymphocyte ratio (NLR) and tumor diameter in patients with gastric cancer (all P<0.05). The 5-year disease-free survival rate and 5-year disease-specific survival rate of all the patients was 45.5% and 50.1%, respectively. Univariate survival analysis showed that age, NLR, PLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-free survival rate (all P<0.05); Age, NLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-specific survival rate (all P<0.05). Multivariate survival analysis showed that high NLR level (HR=1.501, 95%CI: 1.136-1.984), late TNM stage (HR=2.559, 95%CI: 1.850-3.539), DROSD (HR=2.093, 95%CI: 1.571-2.788) and no adjuvant chemotherapy (HR=1.583, 95%CI: 1.204-2.083) were independent risk factor for the 5-year disease-free survival rate (all P<0.05). Late TNM stage (HR=1.938, 95%CI: 1.395-2.692), DROSD (HR=1.566, 95%CI: 1.180-2.078) and no adjuvant chemotherapy (HR=1.336, 95%CI: 1.016-1.758) were independent risk factors for the 5-year disease-free survival rate (all P<0.05). For stage Ⅰ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 78.6% and 83.7%, respectively; and the 5-year disease-specific survival rates was 85.7% and 89.8%, respectively (both P>0.05). For stage Ⅱ and Ⅲ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 15.4% and 48.8%, respectively, and the 5-year disease-specific survival rates was 17.3% and 54.0%, respectively (all P<0.001). Conclusion: As an imaging evaluation method, spleen density is a new tool, which can be used as a prognostic indicator for gastric cancer patients.


Assuntos
Neoplasias Gástricas , Adulto , Idoso , Idoso de 80 Anos ou mais , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Baço/patologia , Neoplasias Gástricas/cirurgia
2.
Front Immunol ; 12: 617032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194419

RESUMO

Stroke is a multiphasic process, and the initial ischemic phase of neuronal damage is followed by secondary innate and adaptive responses that unfold over days after stroke, offer a longer time frame of intervention, and represent a novel therapeutic target. Therefore, revealing the distinct functions of immune cells in both brain and periphery is important for identification of immunotherapeutic targets for stroke to extend the treatment time window. In this paper an examination of the cellular dynamics of the immune response in the central nervous system (CNS) and periphery provoked by cerebral ischemia is provided. New data is presented for the number of immune cells in brain and spleen of mice during the 7 days following middle cerebral artery occlusion (MCAO). A novel analysis of the correlation among various cell types in the brain and spleen following stroke is presented. It is found that the infiltrated macrophages in the ischemic hemisphere positively correlate with neutrophils which implies their synergic effect in migrating into the brain after stroke onset. It is noted that during infiltration of adaptive immune cells, the number of neutrophils correlate positively with T cells, which suggests neutrophils contribute to T cell infiltration in the stroked brain. Furthermore, the correlation among neurological deficit and various immune cells suggests that microglia and splenic adaptive immune cells (T and B cells) are protective while infiltrating peripheral myeloid cells (macrophage and neutrophils) worsen stroke outcome. Comprehension of such immune responses post cerebral ischemia is crucial for differentiating the drivers of outcomes and also predicting the stroke outcome.


Assuntos
Isquemia Encefálica/imunologia , Encéfalo/imunologia , Infarto da Artéria Cerebral Média/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Baço/imunologia , Linfócitos T/imunologia , Animais , Encéfalo/patologia , Movimento Celular , Modelos Animais de Doenças , Humanos , Imunidade Celular , Camundongos , Camundongos Endogâmicos C57BL , Neuroimunomodulação , Baço/patologia
3.
Exp Parasitol ; 228: 108135, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34284027

RESUMO

Trypanosoma brucei rhodesiense is the causative agent for Rhodesian human African trypanosomiasis. The disease is considered acute, but varying clinical outcomes including chronic infections have been observed. The basis for these different clinical manifestations is thought to be associated with a combination of parasite and host factors. In the current study, Trypanosoma brucei rhodesiense strains responsible for varying infection outcomes were sought using mouse model. Clinical rHAT parasite isolates were subjected to PCR tests to confirm presence of the serum resistance associated (SRA) gene. Thereafter, four T. b. rhodesiense isolates were subjected to a comparative pathogenicity study using female Swiss white mice; the parasite strains were compared on the basis of parasitaemia, host survival time, clinical and postmortem biomarkers of infection severity. Isolates identified to cause acute and chronic disease were compared for establishment in insect vector, tsetse fly. The mouse survival time was significantly different (Log-rankp = 0.0001). With mice infected with strain KETRI 3801 exhibiting the shortest survival time (20 days) as compared to those infected with KETRI 3928 that, as controls, survived past the 60 days study period. In addition, development of anaemia was rapid in KETRI 3801 and least in KETRI 3928 infections, and followed the magnitude of survival time. Notably, hepatosplenomegaly was pronounced with longer survival. Mouse weight and feed intake reduced (KETRI 3801 > KETRI 2636 > EATRO 1762) except in KETRI 3928 infections which remained similar to controls. Comparatively, acute to chronic infection outcomes is in the order of KETRI 3801 > KETRI 2636 > EATRO 1762 > KETRI 3928, indicative of predominant role of strain dependent factors. Further, KETRI 3928 strain established better in tsetse as compared to KETRI 3801, suggesting that transmission of strains causing chronic infections could be common. In sum, we have identified Trypanosoma brucei rhodesiense strains that cause acute and chronic infections in mice, that will be valuable in investigating pathogen - host interactions responsible for varying disease outcomes and transmission in African trypanosomiasis.


Assuntos
Trypanosoma brucei rhodesiense/patogenicidade , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/parasitologia , Animais , Ingestão de Alimentos , Feminino , Modelos Lineares , Fígado/patologia , Masculino , Camundongos , Tamanho do Órgão , Parasitemia/parasitologia , Baço/patologia , Trypanosoma brucei rhodesiense/isolamento & purificação , Virulência
4.
Exp Parasitol ; 228: 108137, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34298076

RESUMO

Leishmaniasis is remaining as one of the important health problems of many countries around the world. The histopathology of the disease and the effects of the parasite on various tissues have not yet been fully elucidated. The current study aimed to evaluate the stereological features of the liver, spleen, and bone of hamsters infected with Leishmania infantum. In this experimental study, the L. infantum parasite was mass cultivated in a culture medium. Then, 15 golden hamsters were selected, of which 5 animals were considered as controls and another 10 animals were injected intravenously, with 1 × 108 promastigotes of L. infantum. Four months later, the hamsters were euthanized and impression smears were prepared from the liver and spleen. Moreover, pathology slides were prepared from the spleen, liver, and femur. The orientated method was used to obtain isotropic uniform random (IUR) sections. For stereological evaluation, the tissues were fixed with formalin buffer, and sections (4 and 25 µm thick) were prepared and stained with Heidenhain's AZAN trichrome and hematoxylin-eosin, respectively. The tissue samples were examined by stereological methods and all changes in the samples of the infected hamsters were compared with the control group. The number of hepatocyte and their nuclei volumes were significantly decreased in the Leishmania-infected group, compared to the control group. The number of Kupffer cells and their volume in the liver of the Leishmania-infected group was higher than that of the control group, and the differences were statistically significant. The volume of trabeculae and central arteries in the spleen of the Leishmania-infected group was lower than that of the control group and the number of lymphocytes and macrophages in the spleen of the Leishmania-infected group was increased compared to the control group. The trabecular volume and the number of osteoblasts and osteoclasts of the femur in Leishmania-infected animals decreased, whereas the volume of bone marrow was significantly raised. Leishmaniasis leads to changes in tissue structure and their function in the host by the involvement of various organs of the immune system including the liver, spleen, and bone. Understanding these changes are important in identifying the effective mechanisms of the parasite and host interaction.


Assuntos
Fêmur/patologia , Leishmania infantum/patogenicidade , Leishmaniose Visceral/patologia , Fígado/patologia , Baço/patologia , Animais , Cricetinae , Eosinófilos/patologia , Fêmur/parasitologia , Hepatócitos/patologia , Macrófagos do Fígado/patologia , Fígado/parasitologia , Macrófagos/patologia , Mesocricetus , Osteoblastos/patologia , Osteoclastos/patologia , Osteócitos/patologia , Baço/parasitologia
5.
Viruses ; 13(6)2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207913

RESUMO

The emergence of a novel goose nephritic astrovirus (GNAstV) has caused economic losses to the Chinese goose industry. High viral load is found in the spleen of goslings infected with GNAstV, but pathological injuries to the spleen due to GNAstV are largely unknown. In this study, 50 two-day-old goslings were infected orally with GNAstV, and 50 goslings were treated with PBS as control. Spleens were collected at different times following infection to assess damage. GNAstV infection caused visceral gout and urate deposition in joints, and resulted in 16% mortality. GNAstV was found in the lymphocytes and macrophages within the spleen. Lymphocyte loss, especially around the white pulp, and destruction and decline in the number of reticular fibers was observed in GNAstV-infected goslings. Moreover, in GNAstV-infected goslings, ultrahistopathological examination found that splenic lymphocytes exhibited condensed chromatin and apoptotic bodies, and reticular cells displayed damage to plasma membrane integrity and swollen mitochondria. Furthermore, TUNEL staining confirmed apoptosis of lymphocytes, and the mRNA levels of Fas and FasL were significantly increased in the GNAstV-infected goslings. In addition, GNAstV infection reduced the number and protein expression of CD8. In conclusion, GNAstV infection causes lymphocyte depletion, reticular cell necrosis, reticular fiber destruction, lymphocyte apoptosis, and reduction in CD8 levels, which contribute to spleen injury.


Assuntos
Apoptose , Avastrovirus/fisiologia , Gansos/virologia , Linfócitos/metabolismo , Doenças das Aves Domésticas/etiologia , Doenças das Aves Domésticas/metabolismo , Animais , Avastrovirus/classificação , Avastrovirus/genética , Biópsia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos , Imuno-Histoquímica , Contagem de Linfócitos , Linfócitos/imunologia , Linfócitos/patologia , Doenças das Aves Domésticas/diagnóstico , Baço/imunologia , Baço/metabolismo , Baço/patologia , Baço/virologia , Carga Viral
6.
J Forensic Sci ; 66(5): 2024-2028, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117775

RESUMO

Autopsy findings in intravenous drug addicts are quite variable and may involve a number of organ systems. Reports of the macroscopic identification at autopsy of components of tablets that have been crushed and injected are, however, exceedingly rare. The case of 34-year-old man who died of zolpidem toxicity on a background of pulmonary hypertension attributed to intravenous injections of crushed tablets is described. A very unusual finding was very fine white stippling on the cut surfaces of both the liver and spleen which was shown on energy-dispersive x-ray spectroscopy (EDS) to be titanium dioxide most likely from the coating of the zolpidem tablets. This case is significant in demonstrating titanium dioxide accumulation within organs at both macroscopic and microscopic levels, with confirmation of exposure by EDS analysis. The clinical significance of exposure to such high levels of titanium dioxide is unclear.


Assuntos
Fígado/patologia , Baço/patologia , Titânio/análise , Adulto , Usuários de Drogas , Humanos , Hipertensão Pulmonar/complicações , Fígado/química , Masculino , Medicamentos Indutores do Sono/envenenamento , Espectrometria por Raios X , Baço/química , Abuso de Substâncias por Via Intravenosa , Comprimidos , Zolpidem/envenenamento
7.
Rev Esp Patol ; 54(3): 165-168, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34175027

RESUMO

The difficulties involved in performing autopsies of patients who had died due to COVID-19 required the use of alternative methods in order to obtain tissue samples of affected organs. We describe the technique of core needle aspiration, without ultrasonographic guidance, which we used in 19 cadavers and which produced a high yield in lungs, heart (>94%) and liver (>89%), thus enabling the study of the morphological changes produced by SARS-CoV-2.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , COVID-19/patologia , Biópsia com Agulha de Grande Calibre/instrumentação , Encéfalo/patologia , COVID-19/prevenção & controle , Cadáver , Humanos , Rim/patologia , Fígado/patologia , Pulmão/patologia , Miocárdio/patologia , Baço/patologia
8.
Cell Res ; 31(8): 836-846, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34135479

RESUMO

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Assuntos
COVID-19/patologia , Pulmão/virologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Autopsia , COVID-19/virologia , China , Estudos de Coortes , Estado Terminal , Feminino , Fibrose , Hospitalização , Humanos , Rim/patologia , Rim/virologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/metabolismo , SARS-CoV-2/genética , Baço/patologia , Baço/virologia , Traqueia/patologia , Traqueia/virologia
9.
J Occup Health ; 63(1): e12235, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34089209

RESUMO

OBJECTIVE: To evaluate the immunotoxicity and effects of noise and/or low-concentration carbon monoxide (CO) exposure on immune organs and immune functions in rats. METHODS: Male Wistar rats exposed to 98 dB(A) white noise and/or 100 ppm CO 4 h/d for 30 d were used to determine the pathological changes in the thymus and spleen, and variations in leukocyte counts, inflammatory factors, and immunoglobulin (Ig) concentrations. RESULTS: The boundaries of the cortex and medulla of the thymus were unclear following noise and combined exposure. The pathological changes in spleen after CO and combined exposure included blurred boundaries of red-pulp and white-pulp, disappearance of normal splenic nodules and neutrophil infiltration. After exposure to noise and in combination, leukocyte and lymphocyte counts decreased significantly. After exposure to low-concentration CO and in combination, serum IgM and IgG levels decreased significantly, but the levels of tumor necrosis factor-α and interferon-γ levels increased significantly. Eosinophils and IgA levels decreased significantly following exposure to noise and/or low concentration of CO, while the level of interleukin-1 increased significantly. Monocytes increased significantly only under noise or CO exposure, but not under combined exposure. CONCLUSIONS: Noise and/or low-concentration CO exposure may suppress innate and adaptive immune functions and induce inflammatory responses. Noise exposure mainly affected the innate immune function of rats, whereas low-concentration CO exposure mainly affected adaptive immune functions. Combined exposure presented higher immunotoxicity than noise or CO alone, suggesting that exposure to noise and low-concentration CO in the living and working environments can affect the immune system.


Assuntos
Monóxido de Carbono/toxicidade , Exposição Ambiental/efeitos adversos , Imunidade , Imunotoxinas/toxicidade , Ruído/efeitos adversos , Imunidade Adaptativa , Animais , Imunidade Inata , Imunoglobulinas/sangue , Mediadores da Inflamação/sangue , Contagem de Leucócitos , Masculino , Ratos , Ratos Wistar , Baço/patologia , Timo/patologia
10.
Medicine (Baltimore) ; 100(26): e26441, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190168

RESUMO

ABSTRACT: This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ±â€Š3.68 (months) and progression-free survival (PFS) was 12.63 ±â€Š4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica/métodos , Hiperesplenismo , Neoplasias Hepáticas , Baço/patologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/estatística & dados numéricos , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Hiperesplenismo/sangue , Hiperesplenismo/complicações , Hiperesplenismo/diagnóstico , Hiperesplenismo/terapia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Índice de Gravidade de Doença
11.
Cell Res ; 31(8): 847-860, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34112954

RESUMO

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.


Assuntos
Antivirais/metabolismo , COVID-19/patologia , Proteínas do Envelope de Coronavírus/metabolismo , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Animais , Antivirais/química , Antivirais/uso terapêutico , Apoptose , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Proteínas do Envelope de Coronavírus/antagonistas & inibidores , Proteínas do Envelope de Coronavírus/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Meia-Vida , Humanos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Baço/metabolismo , Baço/patologia , Carga Viral , Virulência
12.
J Med Microbiol ; 70(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34115583

RESUMO

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.


Assuntos
Antiprotozoários/uso terapêutico , Gossypium , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Administração Tópica , Animais , Antiprotozoários/farmacologia , Feminino , Injeções Intraperitoneais , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/genética , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/metabolismo , Leishmania major/fisiologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/fisiopatologia , Linfonodos/patologia , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Baço/parasitologia , Baço/patologia , Células Th1/imunologia , Transcriptoma
13.
Nat Commun ; 12(1): 3543, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112803

RESUMO

Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs. Exosome retention results in changes in the immune landscape within these organs, coupled with a higher metastatic burden. Strikingly, CCL2-decorated exosomes are directed to a subset of cells that express the CCL2 receptor CCR2, demonstrating that exosome-bound cytokines are a crucial determinant of exosome-cell interactions. In addition to the finding that cytokine-conjugated exosomes are detected in the blood of cancer patients, we discovered that healthy subjects derived exosomes are also associated with cytokines. Although displaying a different profile from exosomes isolated from cancer patients, it further indicates that specific combinations of cytokines bound to exosomes could likewise affect other physiological and disease settings.


Assuntos
Neoplasias da Mama/sangue , Quimiocina CCL2/metabolismo , Exossomos/metabolismo , Receptores CCR2/metabolismo , Microambiente Tumoral , Animais , Neoplasias da Mama/patologia , Citocinas/metabolismo , Exossomos/imunologia , Exossomos/patologia , Feminino , Glicosaminoglicanos/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Proteoglicanas/metabolismo , Receptores de Citocinas/metabolismo , Baço/imunologia , Baço/metabolismo , Baço/patologia , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
14.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946346

RESUMO

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1ß) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.


Assuntos
Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/efeitos adversos , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Biomarcadores , Colite/tratamento farmacológico , Colite/etiologia , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia
15.
Mol Cell Biochem ; 476(10): 3671-3679, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34050900

RESUMO

The trend of consuming food high in calories, fat, and sugar with little nutritional value and reduced physical exercise has resulted in an alarming ratio of overweight and obese subjects worldwide. Low-grade chronic inflammation is the key feature of obesity that causes an increase in pro-inflammatory cytokines and decrease in anti-inflammatory cytokines in circulation. The current study was aimed to investigate the effect of high-fat diet on the architecture of spleen, liver, and skeletal muscle and changes in the expression of hepatic cytokines. Two groups of experimental rats were established, against control that were given different percentage of fats in their diet. After a period of sixteen weeks, rats were dissected and their organs were excised out and processed accordingly. Spleen sections of experimental groups, revealed increased recruitment of lymphocytes, sinusoidal dilatations, necrotic lymphocytes, increased ratio of white-to-red pulp, and hemosiderin and iron deposits in red pulp indicating immune system activation. Hepatic sections showed enlarged sinusoidal spaces, disruptive hepatocytes, necrosis and dilation of portal veins. Sections of skeletal muscle showed degenerating fibers, increased fat accumulation, and recruitment of macrophages. Elevated expression of IFN-γ and decreased expression of IFN-α and IFN-ß cytokines verified the adverse effect of high-fat diet on immune system as well. Fats tend to accumulate in organs due to increased intake of fat-rich diet disturbing their normal function and histology. In addition, gene expression analysis of cytokines confirmed the effect of high-fat diet as an inflammatory agent.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Interferons/metabolismo , Fígado/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Baço/metabolismo , Animais , Fígado/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Músculo Esquelético/patologia , Obesidade/induzido quimicamente , Obesidade/patologia , Ratos , Ratos Wistar , Baço/patologia
16.
J Toxicol Sci ; 46(5): 223-234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952799

RESUMO

Sodium carboxy methyl cellulose (SCMC) is an important absorbable biomaterial for anti-adhesion and hemostasis medical devices used in the abdominal cavity. However, the systemic toxicity of SCMC following intraperitoneal route has not been revealed sufficiently. Three SCMC solutions with gradient concentrations were intraperitoneally injected into 3 groups of rats with the doses of 50 mg/kg, 320 mg/kg and 2000 mg/kg respectively all at once to observe the dose-dependence of systemic reactions of SCMC and 10 rats (5 rats per sex) of each group were sacrificed 3 days, 7 days, 28 days and 90 days after injection to evaluate the time-dependence of the reactions. A range of adverse effects were shown in rats of the high-dose group which were found varied with time extending and virtually disappeared 90 days after injection. Slight reactions were observed in the medium-dose group while negligible effects were found in the low-dose group. The intraperitoneal application of SCMC can induce reversible systemic adverse effects to rats at the dose higher than 320 mg/kg and it is essential to take both dose- and time-dependent effects into account while designing a systemic toxicity study for absorbable biomaterials.


Assuntos
Carboximetilcelulose Sódica/toxicidade , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/patologia , Animais , Relação Dose-Resposta a Droga , Feminino , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia , Útero/efeitos dos fármacos , Útero/patologia
17.
PLoS Med ; 18(5): e1003567, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038421

RESUMO

BACKGROUND: Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. METHODS AND FINDINGS: To identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI -15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI -0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI -15.9% to +25.0%], P. falciparum: +3.2% [CI -3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI -8.7% to +21.1%], P. falciparum: -1.4% [CI -4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. CONCLUSIONS: PET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.


Assuntos
Medula Óssea/parasitologia , Glucose/metabolismo , Fígado/parasitologia , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Baço/parasitologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Malária Falciparum/patologia , Malária Falciparum/fisiopatologia , Malária Vivax/patologia , Malária Vivax/fisiopatologia , Masculino , Plasmodium falciparum , Plasmodium vivax , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Queensland , Coluna Vertebral/metabolismo , Coluna Vertebral/parasitologia , Coluna Vertebral/patologia , Baço/metabolismo , Baço/patologia , Adulto Jovem
18.
Medicine (Baltimore) ; 100(21): e25846, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032697

RESUMO

ABSTRACT: Composite hemangioendothelioma (CHE) is a rare vascular neoplasm of intermediate malignant potential. Only 52 cases have been reported in the English literature, and one case previously reported occurred in the spleen. The purpose of our study was to report a 65-year-old man diagnosed as CHE primary arising from the spleen with multiple metastases.Clinical and imaging features, laboratory tests, and pathological results about CHE were described in detail in this study.The patient presented with multiple lesions in bilateral lungs and spleen that had been incidentally detected by computed tomography (CT). Except for thrombocytopenia, other laboratory tests were not significant. The CT scan of the abdomen revealed multiple round-like and irregularly mixed density masses with unclear borders in enlarged spleen. And contrast enhancement showed mild heterogeneous enhancement. CT scan also showed widespread liver, ribs, lungs, and vertebral bodies metastases. This diagnosis was confirmed by histopathological examination. The patient underwent splenectomy and still survives with tumors after six months followed-up.Due to the lack of specificity of clinical features and laboratory tests, it is necessary to combine imaging features and pathological findings to make a correct diagnosis.


Assuntos
Hemangioendotelioma/diagnóstico , Neoplasias Complexas Mistas/diagnóstico , Baço/patologia , Neoplasias Esplênicas/diagnóstico , Idoso , Hemangioendotelioma/secundário , Hemangioendotelioma/cirurgia , Humanos , Masculino , Neoplasias Complexas Mistas/secundário , Neoplasias Complexas Mistas/cirurgia , Baço/diagnóstico por imagem , Esplenectomia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Front Immunol ; 12: 597595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953706

RESUMO

The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen.


Assuntos
Movimento Celular/imunologia , Infecções por Escherichia coli/imunologia , Escherichia coli/imunologia , Pulmão/imunologia , Neutrófilos/imunologia , Baço/imunologia , Animais , Quimiocina CXCL12/imunologia , Células Endoteliais/imunologia , Células Endoteliais/patologia , Infecções por Escherichia coli/patologia , Feminino , Molécula 1 de Adesão Intercelular/imunologia , Pulmão/patologia , Camundongos , Neutrófilos/patologia , Baço/patologia
20.
Biomed Res Int ; 2021: 5530004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959657

RESUMO

Objectives: To investigate the performance of spleen stiffness (SS) by using two-dimensional shear-wave elastography (2D-SWE) for assessing the severity of gastroesophageal varices (GEVs) after transjugular intrahepatic portosystemic shunt (TIPS). Methods: 102 eligible patients were categorized as in the post-TIPS short-term (n = 69) and long-term (n = 38) follow-up groups. The performance of SS by using 2D-SWE for evaluating the severity of GEVs was compared with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), liver stiffness spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension (PH) risk score, platelet count-to-spleen diameter ratio (PSR), and varices risk score by using receiver operating characteristic (ROC) curve and DeLong test. Results: In the post-TIPS short-term follow-up group, area under the receiver operating characteristic curves (AUCs) of SS were 0.585 for mild (cutoff value = 30.3 kPa), 0.655 for moderate (cutoff value = 30.6 kPa), and 0.739 for severe (cutoff value = 31.9 kPa) GEVs, which were higher than other parameters for severe GEVs. AUCs of SS were lower than other parameters for mild and moderate GEVs, but no difference was found (p > 0.05). In the post-TIPS long-term follow-up group, AUCs of SS were 0.778 for mild (cutoff value = 28.9 kPa), 0.82 for moderate (cutoff value = 29.9 kPa), and 0.824 for severe (cutoff value = 37.7 kPa) GEVs, which were higher than other parameters except for severe GEVs. AUC of SS was lower than other parameters for severe GEVs, but no significant difference was found (p > 0.05). Conclusion: SS is an effective noninvasive tool to predict GEV severity during the post-TIPS follow-up.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Baço , Adulto , Idoso , Área Sob a Curva , Varizes Esofágicas e Gástricas/classificação , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/patologia
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