RESUMO
The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.
Assuntos
Diabetes Mellitus , Pé Diabético , Plasma Rico em Plaquetas , Úlcera Cutânea , Infecção dos Ferimentos , Adulto , Humanos , Reprodutibilidade dos Testes , Cicatrização , Extremidade Inferior , Pé Diabético/terapiaRESUMO
Mycoplasma hyopneumoniae is the etiological agent underlying porcine enzootic pneumonia, a chronic respiratory disease worldwide. The recruitment of plasminogen to the surface and subsequently promotion of plasmin conversion by the surface-located receptor, have been reported to assist the adhesion and invasion of Mycoplasmas. The surface localization and plasminogen-binding ability of M. hyopneumoniae enolase were previously confirmed; however, the biological functions were not be determined, especially the role as a plasminogen receptor. Here, using ELISA and SPR analyses, we confirmed the stable binding of M. hyopneumoniae enolase to plasminogen in a dose-dependent manner. The facilitation of the activation of plasminogen in the presence of tPA and direct activation of plasminogen at low efficiency without tPA addition by M. hyopneumoniae enolase were also determined using a plasmin-specific chromogenic substrate. Notably, the C-terminal and N-terminal regions located in M. hyopneumoniae enolase play an important role in plasminogen binding and activation. Additionally, we demonstrate that M. hyopneumoniae enolase can competitively inhibit the adherence of M. hyopneumoniae to PK15 cells. These results provide insight into the role of enolase in M. hyopneumoniae infection, a mechanism that manipulates the proteolytic system of the host.
Assuntos
Mycoplasma hyopneumoniae , Animais , Suínos , Mycoplasma hyopneumoniae/metabolismo , Plasminogênio/metabolismo , Fibrinolisina/metabolismo , Fosfopiruvato Hidratase , Adesinas Bacterianas/metabolismoRESUMO
Appendiceal mucinous neoplasms (AMNs), characterized by expansile or "pushing" growth of neoplastic epithelium through the appendix wall, are sometimes accompanied by peritoneal involvement, the extent and grade of which largely determine clinical presentation and long-term outcomes. However, the prognosis of tumors entirely confined to the appendix is still debated and confusion remains regarding their biologic behavior and, consequently, their clinical management and even diagnostic nomenclature. We evaluated AMNs limited to the appendix from 337 patients (median age: 58 years, interquartile range (IQR): 47-67), 194 (57.6%) of whom were women and 143 (42.4%) men. The most common clinical indication for surgery was mass or mucocele, in 163 (48.4%) cases. Most cases (N = 322, 95.5%) comprised low-grade epithelium, but there were also 15 (4.5%) cases with high-grade dysplasia. Lymph nodes had been harvested in 102 (30.3%) cases with a median 6.5 lymph nodes (IQR: 2-14) per specimen for a total of 910 lymph nodes examined, all of which were negative for metastatic disease. Histologic slide review in 279 cases revealed 77 (27.6%) tumors extending to the mucosa, 101 (36.2%) to submucosa, 33 (11.8%) to muscularis propria, and 68 (24.4%) to subserosal tissues. In multivariate analysis, deeper tumor extension was associated with older age (p = 0.032; odds ratio (OR): 1.02, 95% confidence intervals (CI): 1.00-1.03), indication of mass/mucocele (p < 0.001; OR: 2.09, CI: 1.41-3.11), and wider appendiceal diameter, grossly (p < 0.001; OR: 1.61, CI: 1.28-2.02). Importantly, among 194 cases with at least 6 months of follow-up (median: 56.1 months, IQR: 24.4-98.5), including 9 high-grade, there was no disease recurrence/progression, peritoneal involvement (pseudomyxoma peritonei), or disease-specific mortality. These data reinforce the conclusion that AMNs confined to the appendix are characterized by benign biologic behavior and excellent clinical prognosis and accordingly suggest that revisions to their nomenclature and staging would be appropriate, including reverting to the diagnostic term mucinous adenoma in order to accurately describe a subset of them.
Assuntos
Neoplasias do Apêndice , Produtos Biológicos , Mucocele , Neoplasias Epiteliais e Glandulares , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias do Apêndice/patologia , Mucocele/complicações , Neoplasias Peritoneais/patologia , Recidiva Local de Neoplasia , Pseudomixoma Peritoneal/complicações , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/cirurgia , PrognósticoRESUMO
African swine fever virus (ASFV) is the pathogen of African swine fever, a highly contagious and fatal disease of wild boar and domestic pigs. The flow of ASFV through pork products is more concealed, higher risky, and more difficult to prevent and control. Presently, on-site ASFV detection methods in preclinical infected pigs and circulated pork products are lacking. Here, fluorescent test strip-based rapid ASFV detection method in pork was established combined with recombinase aided amplification (RAA) and quantum dot microspheres (QDMs). This method is specific to ASFV with no cross-reactivity to pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). The method also showed highly sensitivity with a detection limit of 1 copy for ASFV plasmid templates containing B646L gene and 100 copies/g for DNA extracts from clinical pork samples within a short detection time of less than 25 min. Additionally, the method showed 99.17% consistency with real-time PCR in the ASFV detection of 120 clinical pork samples. Overall, the QDMs-based test strip method provides specific, sensitive, rapid, and simple detection of ASFV in pork, which may contribute to maintain the food safety of pork products, and facilitate ASFV traceability and prevention. Rapid and sensitive detection of African swine fever virus in pork by QDMs based test strip assay.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Carne de Porco , Pontos Quânticos , Carne Vermelha , Febre Suína Africana/diagnóstico , Vírus da Febre Suína Africana/genética , Animais , Hidrolases , Microesferas , Recombinases , SuínosRESUMO
Extra-axial chordoma is a rare neoplasm of extra-axial skeleton and soft tissue that shares identical histomorphologic and immunophenotypic features with midline chordoma. While genetic changes in conventional chordoma have been well-studied, the genomic alterations of extra-axial chordoma have not been reported. It is well known that conventional chordoma is a tumor with predominantly non-random copy number alterations and low mutational burden. Herein we describe the clinicopathologic and genomic characteristics of six cases of extra-axial chordoma, with genome-wide high-resolution single nucleotide polymorphism array, fluorescence in situ hybridization and targeted next-generation sequencing (NGS) analysis. The patients presented at a mean age of 33 years (range: 21-54) with a female to male ratio of 5:1. Four cases were histologically conventional type, presented with bone lesions and three of them had local recurrence. Two cases were poorly differentiated chordomas, presented with intra-articular soft tissue masses and both developed distant metastases. All cases showed brachyury positivity and the two poorly differentiated chordomas showed in addition loss of INI-1 expression by immunohistochemical analysis. Three of four extra-axial conventional chordomas showed simple genome with loss of chromosome 22 or a heterozygous deletion of SMARCB1. Both poorly differentiated chordomas demonstrated a complex hyperdiploid genomic profile with gain of multiple chromosomes and homozygous deletion of SMARCB1. Our findings show that heterozygous deletion of SMARCB1 or the loss of chromosome 22 is a consistent abnormality in extra-axial chordoma and transformation to poorly differentiated chordoma is characterized by homozygous loss of SMARCB1 associated with genomic complexity and instability such as hyperdiploidy.
Assuntos
Biomarcadores Tumorais/genética , Cordoma/genética , Proteínas Fetais/genética , Proteína SMARCB1/genética , Proteínas com Domínio T/genética , Adulto , Cordoma/patologia , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Feminino , Deleção de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
MicroRNA (miRNA) has received widespread attention for its role in several key cellular processes such as cell differentiation, cell proliferation, apoptosis, and autoimmune diseases. Although we now have a good understanding of miRNA expression and function, our knowledge regarding the molecular mechanism of long non-coding RNA (lncRNA) is still in its infancy. In this review, we will briefly introduce the definition and function of lncRNA and summarize the interactions between lncRNA and miRNA and their research progress in rheumatoid arthritis (RA). The expression of miR-16, miR-146a, miR-155, and miR-223 and the interactions between HOTAIR and miR138, ZFAS1 and miR-27a, and GAPLINC and miR-575 are representative examples that may augment the understanding of the pathogenesis of RA and help in the development of new biomarkers and target therapies.
Assuntos
Artrite Reumatoide , MicroRNAs , RNA Longo não Codificante , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Humanos , CamundongosRESUMO
Lentiviruses such as HIV-1 encode envelope glycoproteins (Env) with long cytoplasmic tails (CTs) that include motifs mediating interactions with host-cell-trafficking factors. We demonstrated recently that Rab11-family interacting protein 1C (FIP1C) is required for CT-dependent incorporation of Env into HIV-1 particles. Here, we used viruses bearing targeted substitutions within CT to map the FIP1C-dependent incorporation of Env. We identified YW795 as a critical motif mediating cell-type-dependent Env incorporation. Disruption of YW795 reproduced the cell-type-dependent particle incorporation of Env that had previously been observed with large truncations of CT. A revertant virus bearing a single amino acid change near the C terminus of CT restored wild-type levels of Env incorporation, Gag-Env colocalization on the plasma membrane, and viral replication. These findings highlight the importance of YW795 in the cell-type-dependent incorporation of Env and support a model of HIV assembly in which FIP1C/RCP mediates Env trafficking to the particle assembly site.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteína gp41 do Envelope de HIV/fisiologia , HIV-1/fisiologia , Proteínas de Membrana/fisiologia , Motivos de Aminoácidos , Substituição de Aminoácidos , Linhagem Celular , Membrana Celular/virologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteína gp41 do Envelope de HIV/química , Proteína gp41 do Envelope de HIV/genética , HIV-1/genética , Células HeLa , Humanos , Mutagênese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Linfócitos T/virologia , Tirosina/química , Vírion/fisiologia , Montagem de Vírus , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismoRESUMO
UNLABELLED: The assembly and release of retroviruses from the host cells require dynamic interactions between viral structural proteins and a variety of cellular factors. It has been long speculated that the actin cytoskeleton is involved in retrovirus production, and actin and actin-related proteins are enriched in HIV-1 virions. However, the specific role of actin in retrovirus assembly and release remains unknown. Here we identified LIM kinase 1 (LIMK1) as a cellular factor regulating HIV-1 and Mason-Pfizer monkey virus (M-PMV) particle release. Depletion of LIMK1 reduced not only particle output but also virus cell-cell transmission and was rescued by LIMK1 replenishment. Depletion of the upstream LIMK1 regulator ROCK1 inhibited particle release, as did a competitive peptide inhibitor of LIMK1 activity that prevented cofilin phosphorylation. Disruption of either ROCK1 or LIMK1 led to enhanced particle accumulation on the plasma membrane as revealed by total internal reflection fluorescence microscopy (TIRFM). Electron microscopy demonstrated a block to particle release, with clusters of fully mature particles on the surface of the cells. Our studies support a model in which ROCK1- and LIMK1-regulated phosphorylation of cofilin and subsequent local disruption of dynamic actin turnover play a role in retrovirus release from host cells and in cell-cell transmission events. IMPORTANCE: Viruses often interact with the cellular cytoskeletal machinery in order to deliver their components to the site of assembly and budding. This study indicates that a key regulator of actin dynamics at the plasma membrane, LIM kinase, is important for the release of viral particles for HIV as well as for particle release by a distantly related retrovirus, Mason-Pfizer monkey virus. Moreover, disruption of LIM kinase greatly diminished the spread of HIV from cell to cell. These findings suggest that LIM kinase and its dynamic modulation of the actin cytoskeleton in the cell may be an important host factor for the production, release, and transmission of retroviruses.
Assuntos
Infecções por HIV/enzimologia , HIV-1/fisiologia , Quinases Lim/metabolismo , Liberação de Vírus , Quinases Associadas a rho/metabolismo , Actinas/metabolismo , Animais , Linhagem Celular , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Quinases Lim/genética , Fosforilação , Retroviridae/fisiologia , Infecções por Retroviridae/enzimologia , Infecções por Retroviridae/genética , Infecções por Retroviridae/virologia , Quinases Associadas a rho/genéticaRESUMO
The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , HIV-1/metabolismo , Proteínas de Membrana/metabolismo , Montagem de Vírus , Internalização do Vírus , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/virologia , Células Cultivadas , Infecções por HIV/metabolismo , Células HeLa , Humanos , Proteínas de Membrana/genética , Transporte Proteico , Interferência de RNA , Replicação Viral , Proteínas rab de Ligação ao GTP/genéticaRESUMO
Platelet-rich plasma (PRP) has been widely used in clinical practice. The mechanism by which PRP promotes tissue repair lies in the release of multiple growth factors upon platelet activation, which accelerates the proliferation and differentiation of repair cells and the synthesis of extracellular matrix. In recent years, as extracellular vesicles (EVs) research has increased and intensified, it has been found that EVs also play an important role in tissue repair. This article provides a comprehensive review of the role of PRP and PRP-derived extracellular vesicles (PRP-EVs) in tissue repair. It discusses the biological characteristics, extraction, identification, activation, and preservation of PRP-EVs. It also reviews their applications in orthopedics and wound repair. The article highlights the importance of PRP-EVs in modern medicine and suggests that they could be a promising natural nanocarrier.
The review discusses extracellular vesicles derived from platelet-rich plasma(PRP-EVs). PRP promotes repair of the body's tissues and has been used in clinical practice for many years. Extracellular vesicles are granules released by cells that facilitate intercellular communication. Studies in recent years have revealed that PRP can also release extracellular vesicles that participate in the repair process of tissues. Here, we elaborate on PRP-EVs. Regarding PRP-EVs, current studies are limited to the animal level and have not yet been used in the clinical setting.
Assuntos
Vesículas Extracelulares , Plasma Rico em Plaquetas , Humanos , Plaquetas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
Background: Breast cancer (BC) is a malignancy that is inadequately treated and poses a significant global health threat to females. The aberrant expression of long noncoding RNAs (lncRNAs) acts as a complex with a precise regulatory role in BC progression. LINC00969 has been linked to pyroptotic cell death and resistance to gefitinib in lung cancer cells. However, the precise function and regulatory mechanisms of LINC00969 in BC remain largely unexplored. Methods: Cell proliferation, migration, and invasion of BC cells were evaluated using CCK-8 and Transwell assays. Western blotting was employed to analyze the protein expression levels of HOXD8, ILP2, PI3K, t-AKT, and p-AKT. Results: LINC00969 was drastically reduced in BC tissues LINC00969 overexpression markedly suppressed proliferation, migration, and invasion, and blocked PI3K and p-AKT protein expression in MCF-7 cells. Activation of the PI3K/AKT pathway reversed the suppressive effect of LINC0096 overexpression on the proliferation, migration, and invasion of MCF-7 cells. Moreover, LINC00969 overexpression enhanced HOXD8 and blocked ILP2 protein expression in MCF-7 cells. In contrast, activating the PI3K/AKT pathway had no effect on HOXD8 and blocked ILP2 protein expression in MCF-7 cells overexpressing LINC00969. HOXD8 knockdown enhanced ILP2, PI3K, and p-AKT protein expression, and the proliferation, migration, and invasion of MCF-7 cells co-transfected with si-HOXD8 and ov-LINC00969. LINC00969 regulated HOXD8 via binding to miR-425-5p. Conclusion: LINC00969 inhibits the proliferation and metastasis of BC cells by regulating PI3K/AKT phosphorylation through HOXD8/ILP2.
Assuntos
Neoplasias da Mama , MicroRNAs , Feminino , Humanos , Neoplasias da Mama/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Fosfatidilinositol 3-Quinases/genética , Linhagem Celular Tumoral , Fosforilação/genética , Proliferação de Células/genética , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genéticaRESUMO
Primary malignant melanoma of the gallbladder is an extremely rare tumor with approximately 39 cases described in the literature so far. However, since the first case was reported in 1907, it remains controversial whether gallbladder involvement in malignant melanoma is primary or metastatic. Here, we report a case of primary malignant melanoma of the gallbladder. A 52-year-old male presented to the emergency department with right upper quadrant abdominal pain and was found to have tumefactive sludge filling the majority of the gallbladder with possible gallbladder wall thickening on ultrasonography. A laparoscopic cholecystectomy was performed for presumed acute cholecystitis. Histopathologic examination of the gallbladder revealed malignant melanoma arising from the mucosa of the gallbladder. Further clinical investigation excluded other primary sites, supporting a diagnosis of primary malignant melanoma of the gallbladder.
RESUMO
Tumor budding at the invasive tumor front (peritumoral budding) is an established prognostic factor in colorectal cancer. However, the significance of intratumoral budding (ITB) in pretreatment biopsies is still uncertain. Our study aims to investigate the association of ITB and tumor microenvironment in pretreatment rectal cancer biopsies with pathologic response to neoadjuvant chemoradiotherapy. Pretreatment biopsies of low-grade rectal cancer from 37 patients who underwent resection after neoadjuvant chemoradiotherapy were retrospectively reviewed to evaluate ITB, type of tumor stroma, and intraepithelial lymphocytes. ITB was counted on a single hotspot in 1 HPF upon pan-keratin immunohistochemical staining. Intraepithelial lymphocytes was graded semiquantitatively as "absent" (≤2/HPF) or "present" (>2/HPF). The tumor stroma was classified as either immature type or maturing type. In pretreatment biopsies, ITB was observed in 34/37 patients (92%). High-grade ITB was significantly associated with a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P<0.001; and higher posttreatment T stage, P=0.002). Immature type of stroma was significantly associated with both high-grade ITB in biopsies (P=0.02) and a poor pathologic response to neoadjuvant chemoradiotherapy (tumor regression score 2 to 3, P=0.005). In multivariate analysis, ITB and the type of stroma remained the significant parameters for prediction of response to neoadjuvant treatment. Our study indicates that ITB and tumor microenvironment in pretreatment biopsies are strong predictors of response to neoadjuvant chemoradiotherapy, which may assist risk stratification and clinical management in rectal cancer patients.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Biópsia , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento , Microambiente TumoralRESUMO
OBJECTIVE: To study the effect of 1,2,6-Tri-O-galloyl-beta-D-glucopyranose (BJA32531) on the miRNA expression during BJA32531-induced cytotoxicity in human HepG2 hepatocarcinoma cells. METHODS: Cell proliferation was assessed using a colorimetric assay (cell counting kit-8). Apoptosis was assessed by annexin V and propidium iodide staining. The miRNA expression profile of the cancer cells was analyzed by a miRNA array and quantitative real-time PCR. RESULTS: BJA32531 inhibited the cell proliferation and increased apoptosis in HepG2 cancer cells. Cellular exposure to BJA32531 influenced the miRNA expression pattern in the cells, including 19 upregulated and 85 down-regulated miRNAs in the cells. The up-regulations of let-7a and miR-10b as well as the down-regulations of miR-132 and miR-125b were verified to be consistent with the the results of the miRNA array. CONCLUSION: Our study suggests that the mechanisms by which BJA32531 exerted the antiproliferative effects on HepG2 cancer cells may be related to its regulation of miRNA.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/metabolismo , Polifenóis/farmacologia , Apoptose/efeitos dos fármacos , Balanophoraceae/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Estrutura Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Polifenóis/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Breast cancer is one of the most common malignant tumors in women. Although a number of homeobox (HOX) genes are known to serve an important role in breast cancer, the role of HOXD8 in breast cancer remains unclear. The aim of the present study was to investigate the role of HOXD8 in the physiological behaviors of breast cancer cells. The Gene Expression Profiling Interactive Analysis database was used to analyze the expression of HOXD8 in patients with breast cancer and in healthy subjects. Western blotting was performed to determine the expression levels of HOXD8 in several breast cancer cell lines; subsequently, HOXD8 expression was knocked down and overexpressed in MCF-7 cells. Cell Counting Kit-8, colony formation, wound healing and Transwell assays were used to evaluate the effects of HOXD8 on breast cancer cell viability, proliferation, migration and invasion, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to identify the binding sites between HOXD8 and inhibitor of apoptosis-like protein-2 (ILP2). In addition, ILP2 expression levels were knocked down in MCF-7 cells. The results demonstrated that the expression levels of HOXD8 were significantly downregulated in breast cancer tissues and cell lines, and that the overexpression of HOXD8 inhibited the proliferation, invasion and migration of cancer cells. HOXD8 was shown to bind to the ILP2 promoter to regulate the expression of ILP2. Furthermore, ILP2 knockdown reversed the effects of HOXD8 knockdown on breast cancer cell proliferation, invasion and migration. In conclusion, the findings of the present study suggested that HOXD8 may inhibit the proliferation, migration and invasion of breast cancer cells by downregulating ILP2 expression.
RESUMO
Chronic schistosome infection results in the suppression of host immune responses, allowing long-term schistosome survival and restricting pathology. Current theories suggest that Treg play an important role in this regulation. However, the mechanism of Treg induction during schistosome infection is still unknown. The aim of this study was to determine the mechanism behind the induction of CD4(+)CD25(+) T cells by Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as to elucidate the cellular and molecular basis for the induction of CD4(+)CD25(+) T cells during S. japonicum infection. Mice immunized with SJMHE1 or spleen and LN cells from naïve mice pretreated with SJMHE1 in vitro all displayed an increase in CD4(+)CD25(+) T-cell populations. Release of IL-10 and TGF-beta by SJMHE1 stimulation may contribute to suppression. Adoptively transferred SJMHE1-induced CD4(+)CD25(+) T cells inhibited delayed-type hypersensitivity in BALB/c mice. Additionally, SJMHE1-treated APC were tolerogenic and induced CD4(+) cells to differentiate into suppressive CD4(+)CD25(+) Treg. Furthermore, our data support a role for TLR2 in SJMHE1-mediated CD4(+)CD25(+) Treg induction. These findings provide the basis for a more complete understanding of the S. japonicum-host interactions that contribute to host homeostatic mechanisms, preventing an excessive immune response.
Assuntos
Antígenos de Helmintos/imunologia , Interações Hospedeiro-Parasita/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T Reguladores/imunologia , Receptor 2 Toll-Like/imunologia , Animais , Diferenciação Celular/imunologia , Chaperonina 60/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Ativação Linfocitária/imunologia , Macrófagos/citologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Schistosoma japonicum/imunologiaRESUMO
Among the proteins encoded by human and simian immunodeficiency viruses (HIV and SIV) at least three, Vif, Vpu and Vpr, subvert cellular ubiquitin ligases to block the action of anti-viral defenses. This review focuses on Vpr and its HIV2/SIV counterparts, Vpx and Vpr, which all engage the DDB1.Cullin4 ubiquitin ligase complex through the DCAF1 adaptor protein. Here, we discuss the multiple functions that have been linked to Vpr expression and summarize the current knowledge on the role of the ubiquitin ligase complex in carrying out a subset of these activities.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas Culina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Produtos do Gene vpr/metabolismo , HIV-1/metabolismo , Sequência de Aminoácidos , Produtos do Gene vpr/química , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Dados de Sequência Molecular , Proteínas Serina-Treonina Quinases , Ubiquitina-Proteína Ligases , Replicação ViralRESUMO
In chronic infectious diseases, such as schistosomiasis, pathogen growth and immunopathology are affected by the induction of a proper balanced Th1/Th2 response to the pathogen and by antigen-triggered activation-induced T cell death. Here, by using S. japonicum infection or schistosome antigens-immunized mouse model, or antigens in vitro stimulation, we report that during the early stage of S. japonicum infection, nonegg antigens trigger Th2 cell apoptosis via the granzyme B signal pathway, contributing to Th1 polarization, which is thought to be associated with worm clearance and severe schistosomiasis. Meanwhile, after the adult worms lay their eggs, the egg antigens trigger Th1 cell apoptosis via the caspase pathway, contributing to Th2 polarization, which is associated with mild pathology and enhanced survival of both worms and their hosts. Thus, our study suggests that S. japonicum antigen-induced Th1 and Th2 cell apoptosis involves the Th1/Th2 shift and favorites both hosts and parasites.
Assuntos
Antígenos de Helmintos/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th1/imunologia , Células Th2/imunologia , Amebicidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Artemisininas/farmacologia , Artesunato , Linfócitos T CD4-Positivos/imunologia , Caspases/imunologia , Feminino , Granzimas/imunologia , Fígado/parasitologia , Fígado/patologia , Ativação Linfocitária , Veias Mesentéricas/parasitologia , Veias Mesentéricas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Ovos de Parasitas , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/parasitologia , Transdução de SinaisRESUMO
Acinar cystic transformation (ACT), also known as "acinar cell cystadenoma," is a rare and newly recognized benign pancreatic cystic neoplasm. However, its true malignant potential remains unknown. Here, we report a case of ACT with 15-year follow-up. A 10-year-old female initially presented with abdominal pain and was found to have a cystic lesion in the region of pancreatic head on computed tomography scan. She underwent an exploratory laparotomy, and the intraoperative biopsy of the cyst wall showed a true pancreatic cyst without malignancy. Her symptoms subsequently resolved, and she was placed under close ultrasound surveillance. For the next fifteen years, the patient was asymptomatic without any complications and had a successful pregnancy. Surveillance showed the tumor grew in size from 4.2 cm to 6.2 cm in diameter. In the latest five months, she noted occasional abdominal pain. A pylorus-preserving pancreaticoduodenectomy was performed. The resected cystic lesion was multilocular and lined by a single layer of bland epithelium ranging from nondescript flat/cuboidal epithelium to apparent acinar cells which were strongly positive for trypsin, so the final diagnosis was confirmed to be ACT. The prior biopsy was retrospectively reviewed to reveal similar epithelial lining. To the best of our knowledge, this is the longest period of follow-up for ACT to date. Our findings suggest that ACT is a slow-growing neoplasm without malignant transformation after fifteen years. Therefore, we recommend biopsy for histologic diagnosis followed by close ultrasound surveillance without surgical intervention in asymptomatic or young ACT patients.
RESUMO
â¢Extrauterine adenomyoma cannot be solely diagnosed on the basis of radiographic appearance.â¢There are five theories for the pathophysiology of extrauterine adenomyomas.â¢Surveillance and treatment range from none to ovarian suppression.