ABSTRACT
Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Subject(s)
Humans , Prognosis , Osteosarcoma/genetics , Immunotherapy , Macrophages , Transcription Factors , Bone Neoplasms/genetics , Homeodomain Proteins , Repressor ProteinsABSTRACT
Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.
ABSTRACT
Purpose: To study the uptake capacity of cells from the reticuloendothelial system after irradiation with high-energy X-rays. Methods: Eighteen male Wistar rats were distributed in three groups: group A (n = 6): control, unirradiated animals studied alongside animals from group B; group B (n = 6) and group C (n = 6): animals irradiated and studied after 24 and 48 hours, respectively. The rats were anesthetized and placed on a 10 MV linear accelerator. Next, they were irradiated in the abdominal region, with 8 Gy. Twenty-four (groups A and B) and 48 hours later (group C), a colloidal carbon solution (1 mL/kg) was intravenously injected in the tail vein. Fifty minutes later, the spleens and livers were withdrawn and prepared to be studied. Kupffer cells and splenic macrophages containing carbon pigments were counted in an optical microscope. Arithmetic means were calculated for each group and compared among them. Results: X-rays were associated with a reduced number of Kupffer cells containing colloidal carbon, proliferation and enlargement of biliary ducts, hypoplasia, and hepatocyte necrosis. In the irradiated spleen, the colloidal carbon uptake was concentrated in the marginal zone around the white pulp, with an inexpressive uptake of pigments by macrophages from white and red pulps. Conclusions: The X-rays in the rat abdomen are associated with a reduction in the Kupffer cells uptake of colloidal carbon, hepatocyte disorders, bile duct proliferation, and splenic uptake of colloidal carbon concentrated in the marginal zone.
Subject(s)
Animals , Rats , Mononuclear Phagocyte System , Radiotherapy, High-Energy , Kupffer CellsABSTRACT
Liver nonparenchymal cells play an important role in hepatitis B virus (HBV)-related liver diseases, and the activation of hepatic stellate cells (HSCs) and their interactions with intrahepatic cells are the main cause of liver fibrosis. This article mainly introduces HBV-induced liver inflammation and the interaction between innate immune cells and HSCs and briefly describes the role of monocytes/macrophages and natural killer cells in the activation and killing of HSCs and the immunomodulatory effect of HSCs in the presence of HBV.
ABSTRACT
Although many studies have focused on how material surface modifications can promote stem cell differentiation toward osteogenic osteoblasts, little is known about the reaction between material surface and other cells, including osteoclasts and foreign body giant cells. Dental implant osseointegration results from the functional coupling and equilibrium not only between osteoblasts and osteoclasts but also between bone tissue and immune system. Osteoclasts and foreign body giant cells share the same origin, monocyte/macrophage lineage cells, which have initially got concerns in the field of implant osseointegration with regard to their peri-implant distribution and biological functions. Up-to-date data has shown that cells of monocyte/macrophage lineage origin manifest key roles in the establishment of peri-implant osseointegration and the long-term maintenance of marginal bone level and the prevalence of peri-implantitis. However, preliminary progress has been made in the subtypes, phenotypes vs. genotypes, and functions of monocyte/macrophage-lineage-originated cells on the osseointegration interface, quite a lot of facts still remain unclear, especially the potential and the rapeutic targets which could coordinate the cellular peri-implant microenvironment and the implant osseointegrated interface in the short and long term. This review will focus on the current progress in the function of monocyte/macrophage-lineage origin cells on the peri-implant osseointegration interface.
ABSTRACT
This case illustrates a rare presentation (as lymphadenopathy and fever) of one of the most common zoonotic diseases worldwide-brucellosis-in a 22-year-old Brazilian male (a chef) who had recently returned to Brazil after having lived in and traveled around Europe for one year. The histopathology, clinical history, and response to treatment were all consistent with a diagnosis of brucellosis, which was confirmed by PCR in a urine sample. We also review some aspects of brucellosis, such as the clinical features, diagnosis, and management.
Ilustramos aqui um caso de uma apresentação atípica (na forma de linfadenomegalia e febre) de uma das doenças zoonóticas mais comuns no mundo - brucelose - em um paciente brasileiro de 22 anos (chefe de cozinha) que retornara ao Brasil recentemente após ter morado e viajado na Europa por um ano. A histopatologia, a história clínica e a resposta ao tratamento foram consistentes com o diagnóstico de brucelose, que foi confirmada por PCR em uma amostra de urina. Também revisamos alguns aspectos da brucelose, como manifestações clínicas, diagnóstico e tratamento.
Subject(s)
Female , Humans , Male , Young Adult , Brucellosis/diagnosis , Cooking , Occupational Diseases/diagnosis , Diagnosis, Differential , Europe , Fever/etiology , Lymphatic Diseases/diagnosis , Mediastinum , TravelABSTRACT
Objective To investigate the correlation between the frequency of myeloid-derived suppressor cells (MDSC) and the frequency of regulatory T cells (Treg) in the peripheral blood in patients with chronic hepatitis B (CHB) and its clinical significance.Methods A total of 45 CHB patients including 23 mild-to-moderate CHB patients,22 severe CHB patients,and 15 healthy controls were enrolled.The frequencies of MDSC and Treg in the peripheral blood were studied using flow cytometry and its correlation with clinical data was analyzed by Sepearman correlation analysis.Results The median frequency of MDSC in CHB patients was 0.414％,which was significantly higher than that in healthy controls 0.226％ (Z=-2.356,P=0.018 9).The frequency of MDSC in CHB patients was negatively correlated with the level of alanine transaminase (ALT) and aspartate transaminase (AST) (r=-0.480,-0.478; both P＜0.01),but had no relations with hepatitis B virus (HBV) viral load (r=-0.049,P=0.75).An increase frequency of MDSC was observed in CHB patients with an ALT of 5 × upper limits of normal (ULN) or less or AST of 3 × ULN or less.The frequency of MDSC in CHB patients was positively correlated with that of Treg (r =0.345,P =0.02).Conclusions The activation and proliferation of MDSC may facilitate and maintain HBV persistent infection.The change of the frequency of MDSC is in line with that of Treg,indicating that immunosuppressive functions of MDSC may be related with the development of Treg in CHB.
ABSTRACT
Objective To investigate the effects,mechanisms,and the optimum doses of Rosuvastatin and Losartan on expression of caveolin-1 in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein(ox-LDL).Methods Human-monocyte cells were separated and changed into the human monocyte-macrophage cells.The model of amerosclerosis was set up.These cells were incubated in different doses of Rosuvastatin(0.1,1.0,5.0 μmol/L) and Losartan (10,50,100 μmol/L),and then cultured in combination of two drags (5.0 μmol/L + 100 μmol/L).Expression of caveolin-1 mRNA was determined with real-time fluorescent quantitative polymerase chain reaction (RT-PCR).Results In ox-LDL group,caveolin-1 mRNA was decreased sharply relative to control group [(0.2533 ±0.00973) vs (0.9410 ±0.03677)] in a concentration-dependent manner (P ＜0.01).Compared to ox-LDL group,expressions of Caveolin-1 mRNA were increased gradually in different doses of Rosuvastatin alone and Losartan alone group [(0.5198 ± 0.04840),(0.6183 ± 0.06740),(0.7257 ± 0.03052) vs (0.2533 ± 0.00973) ; (0.3350 ± 0.04177),(0.4428 ± 0.03804),(0.6049 ± 0.02627) vs (0.2533 ± 0.00973)] in a concentration-dependent manner (P ＜ 0.01) ; the summit expressions of caveolin-1 mRNA were emerged in using Rosuvastatin and Losartan together (F =59.119,P ＜ 0.01).Conclusions Rosuvastatin and Losartan may be responsible for the expression of caveolin-1 in human monocyte-macrophage cells that were induced by ox-LDL.The expressions were up-regulated with dose dependent manner of these drugs,and got the crest stage when using optimum doses of Rosuvastatin and Losartan together.
ABSTRACT
Objective To investigate the effects and mechanism of different doses of rosuvastatin on expression of tissue factor(TF) in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein (ox-LDL).Methods The human monocyte-macrophage cells were divided into seven groups:control group,ox-LDL group,poly-insine monophosphate group,different doses of rosuvastatin group(0.01 μmol/L,0.1 μmol/L,1 μmol/L,5 μmol/L).The expression of LOX-1 mRNA and TF mRNA was assayed by RT-PCR.The enzyme-linked immunosorbent assay was performed to determine the protein concentration of TF.Results Effects of different doses of rosuvastatin on expressions of LOX-1mRNA,TF mRNA and TF in cultured human monocyte-macrophage cells induced by ox-LDL:comparison among seven groups,the difference was statistically significant (F =91.334,58.833,103.552,P ＜0.05).Compared with control group,the expressions of LOX-1 mRNA,TF mRNA and TF were increased in the ox-LDL group[(3.25156 ± 0.15772) vs (1 ±0) ;(2.522451 ±0.138967) vs (1 ±0) ;(207.7233± 1.154701)ng/L vs (184.8467 ± 0.871799)ng/L],and they were in a concentration-dependent manner (P ＜ 0.05).Compared with the PolyⅠ group and the different doses of rosuvastatin group,the expressions of LOX-1 mRNA,TF mRNA and TF were in the ox-LDL group,and the different doses of rosuvastatin were decreased by dose-dependent manner.It was in a concentration dependent manner (P ＜ 0.05).Different doses of rosuvastatin were compared between groups (between each group P ＜ 0.05),the difference between each two groups was statistically significant (P ＜ 0.05).Conclusions LOX-1 may be responsible for the expression of TF in Human monocyte-macrophage cells induced by ox-LDL.Rosuvastatin by dose dependent manner and by means of ox-LDL reduced monocyte-macrophage LOX-1 mRNA and TF mRNA expressions,which reduced expression of TF.
ABSTRACT
ObjectiveTo investigate the effects and mechanism of rosuvastatin on the expression of tissue factor in cultured human monocyte-macrophages cells which was induced by oxidized low density lipoprotein(ox-LDL).MethodsThe human monocyte-macrophages cells were divided into four groups:control group,ox-LDL group,Poly-inosine monophosphate (Poly Ⅰ) group,rosuvastatin group.The expression of LOX-1mRNA and TF mRNA was assayed by RT-PCR.The ELISA was performed to determine the protein concentration of TF.ResultsCompared with control group,the expression of LOX-1 mRNA and TF mRNA was increased in the ox-LDL group[ (3.25156±0.15772) vs (1±0) ; (2.522451±0.138967) vs (1±0) ],and it was in a concentration-dependent manner (P＜0.01).Compared with the expression of LOX-1 mRNA in the Poly-inosine monophosphate group and rosuvastatin group,TF mRNA were decreased in the ox-LDL group[ (2.95139±0.157253) vs(3.25156±0.15772) ; (2.877343±0.156558) vs(3.25156±0.15772) ; (1.811956±0.169699) vs (2.522451±0.138967) ; (1.687701±0.174647) vs (2.522451±0.138967)],and it was in a concentration-dependent manner(P＜0.05).Compared with control group,the expression of TF in the ox-LDL group was increased [(207.7233±1.154701) vs (184.8467±0.871799) ],and it was in a concentration-dependent manner (P＜0.01).Compared with the Poly-inosine monophosphate group and rosuvastatin group [(197.8733±1.505003) vs (207.7233±1.154701) ;(202.9567±2.722744)vs(207.7233±1.154701) ],the expression of TF in the ox-LDL group were decreased,and it was in a concentration-dependent manner (P＜0.05).ConclusionsLOX-1 may be responsible for the expression of TF in human monocyte-macrophages cells induced by ox-LDL.Rosuvastatin is able to down-regulate the expression of LOX-1mRNA in human monocyte-macrophages cells through oxLDL,and TF mRNA and TF expression can be reduced.
ABSTRACT
Objective: Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. The objective of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) - control, and Group 2 (n = 8) - animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with 99Tcm was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. Gamma camara was used to measure the radioactivity of these organs and of a blood clot. Results: No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic function, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood in both groups. Conclusions: According to the experiential conditions of this work, acute intake of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice.
Objetivo: Os indivíduos alcoolistas têm uma propensão maior à infecção, especialmente do sistema respiratório. O consumo de álcool inibe tanto de forma direta como indireta o sistema imune. Apesar da extensa literatura existente sobre as repercussões do alcoolismo no sistema imune, os dados referentes à sua interação, quando administrado de forma aguda, na função fagocitária do sistema mononuclear fagocitário (SMF) permanecem controversos. O objetivo do presente trabalho foi verificar a influência do alcoolismo agudo no SMF. Métodos: Foram utilizados 13 camundongos da raça Swiss, distribuídos em dois grupos: Grupo 1 (n = 5): controle, e Grupo 2 (n = 8): animais que receberam 0,5 ml de etanol a 50%, 30 minutos antes do experimento. Decorrido esse tempo, injetaram-se 0,15 ml de enxofre coloidal marcado com 99Tcm na veia jugular. Após uma hora, retirou-se um fragmento de fígado, baço e pulmão, além de um coágulo sanguíneo, os quais foram pesados. A atividade radioativa de cada fragmento foi medida em um aparelho de gama-câmara. Resultados: Ambos os grupos apresentaram maior atividade fagocitária no fígado, seguida pelo baço e pulmão (p = 0,021, para Grupo 1 e p = 0,003, para Grupo 2). O coágulo apresentou a menor quantidade de radiação tanto no Grupo 1 quanto no Grupo 2. Conclusões: Nas condições experimentais deste trabalho, o alcoolismo agudo não influenciou na atividade fagocitária do SMF.
ABSTRACT
OBJETIVOS: Para se evitar o estado asplênico, muitas medidas preservadoras do baço têm sido propostas na literatura, como a esplenorrafia, a esplenectomia parcial com preservação dos vasos hilares e o auto-implante de tecido esplênico. A esplenectomia subtotal, com conservação do pólo superior do baço, nutrido apenas pelos vasos esplenogástricos é uma alternativa quando o pedículo esplênico precisa ser ligado. O objetivo deste estudo foi avaliar a influência das esplenectomias parcial, subtotal e total na distribuição da Escherichia coli no sistema mononuclear fagocitário. MÉTODO: Foram estudados 32 ratos divididos em 4 grupos: operação simulada (mantendo todo o baço), esplenectomia parcial, esplenectomia subtotal e esplenectomia total. Após cinco semanas da operação, uma alíquota de Escherichia coli marcada com 99m-tecnécio foi injetada por via venosa. Após 20 minutos, os animais foram mortos, e o baço, os pulmões e o fígado foram retirados para se verificar a distribuição das bactérias marcadas. RESULTADOS: A quantidade de Escherichia coli no tecido esplênico foi maior no grupo com o baço íntegro em comparação com os grupos esplenectomia parcial e subtotal. A distribuição da bactéria marcada pelo baço não diferiu nos grupos com esplenectomia parcial ou subtotal. A quantidade de bactérias no pulmão foi maior no grupo esplenectomia parcial do que a do grupo com esplenectomia subtotal. Após esplenectomia subtotal, a distribuição da bactéria marcada foi maior no fígado em comparação com a captação desse órgão nos demais grupos. CONCLUSÕES: O pólo superior do baço, suprido apenas pelos vasos esplenogástricos, tem capacidade de remover da circulação bactérias vivas, mostrando que, mesmo sem a vascularização pelo pedículo esplênico, há uma eficiente depuração sangüínea. A distribuição da Escherichia coli pelo sistema mononuclear fagocitário apresenta comportamentos diferentes, dependendo do tipo de esplenectomia a que o animal é submetido.
BACKGROUND: To avoid asplenic state, many approaches preserving the spleen have been proposed, such as splenorraphy, partial splenectomy with hilum vessels preservation and autotransplantation. Subtotal splenectomy preserving the upper splenic pole supplied only by splenogastric vessels, is an alternative when splenic pedicle cannot be maintained. The purpose of this study is to evaluate the influence of partial, subtotal and total splenectomy on Escherichia coli distribution in mononuclear phagocyte system. METHODS: Thirty-two rats were divided into the following 4 groups: sham operation (no splenectomy), partial splenectomy, subtotal splenectomy and total splenectomy. In the fifth week postoperative, an aliquot of Escherichia coli labelled with technetium-99m was intravenously injected. After 20 minutes, the animals were killed to remove spleen, lungs and liver, in order to verify the labelled bacteria distribution. RESULTS: The amount of Escherichia coli in the splenic tissue was greater in the group with intact spleen. The bacteria uptake by the spleen was not different from partial or subtotal splenectomy groups. The amount of bacteria in the lungs was greater in the partial splenectomy group than in the subtotal group. After subtotal splenectomy, the distribution of labelled bacteria was greater in the liver than in the others all groups. CONCLUSIONS: The upper splenic pole, supplied only by splenogastric vessels, is able to remove alive bacteria from the blood stream, showing that, even in absence of splenic pedicle, blood clearance continues to be effective. The distribution of Escherichia coli in mononuclear phagocyte system shows different behaviors, depending on the type of splenectomy.