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The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.
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COVID-19 , SARS-CoV-2 , Animales , Ratones , Conejos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Macaca mulatta , Macrófagos , Nanovacunas , Fagocitosis , Lectinas Similares a la Inmunoglobulina de Unión a Ácido SiálicoRESUMEN
The prognosis of patients with peripheral T-cell lymphoma (PTCL) depends on bone marrow involvement (BMI). The bone marrow (BM) tumor microenvironment in PTCL remains unclear. We performed single-cell RNA sequencing (scRNA-seq) on 11 fresh BM samples from patients with BMI to reveal the associations of immune landscape and genetic variations with the prognosis of PTCL patients. Compared with PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL) had a higher number of T cells, lower number of lymphocytes, and greater inflammation. Immune heterogeneity in AITL is associated with prognosis. In particular, specific T-cell receptor (TCR) T cells are enriched in patients with good response to anti-CD30 therapy. We observed RhoA mutation-associated neoantigens. Chidamide-treated patients had a higher number of CD4+ regulatory cells and a better treatment response compared with other patients. In the nonresponder group, T-cell enrichment progressed to secondary B-cell enrichment and subsequently diffuse large B-cell lymphoma. Moreover, AITL patients with lymphoma-associated hemophagocytic syndrome had more T follicular helper (Tfh) cells with copy number variations in CHR5. To our knowledge, this study is the first to reveal the single-cell landscape of BM microenvironment heterogeneity in PTCL patients with BMI. scRNA-seq can be used to investigate the immune heterogeneity and genetic variations in AITL associated with prognosis.
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Médula Ósea , Linfoma de Células T Periférico , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Médula Ósea/patología , Médula Ósea/inmunología , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Mutación , Receptores de Antígenos de Linfocitos T/genética , Proteína de Unión al GTP rhoA/genética , Adulto , Heterogeneidad GenéticaRESUMEN
Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of pro-inflammatory factors were released. A group of IAV-infected PD-L1+ neutrophils were the major contributor to the first wave at an earlier stage (day 1-3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4+)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1+ neutrophils and Pf4+-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of pro-inflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.
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Virus de la Influenza A/inmunología , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Animales , Plaquetas/inmunología , Quimiocinas/inmunología , Citocinas/inmunología , Femenino , Humanos , Inflamación/patología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Virus de la Influenza A/metabolismo , Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Macrófagos/inmunología , Macrófagos Alveolares/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Infecciones por Orthomyxoviridae/inmunología , Análisis de Secuencia de ARN/métodos , Transducción de Señal/inmunología , Análisis de la Célula Individual/métodosRESUMEN
Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 µg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the animals treated with TBT. The expression of the insulin receptor (IR) signaling cascade, including IR, IR substrate, phosphatidylinositol 3-kinase, Akt, and glucose transporter 4, was inhibited both in the skeletal muscle and the liver, which might be a main reason for the hyperglycemia and hyperinsulinemia. After removing the TBT stress for 60 days, the animals which had received exposure to TBT could recover normoglycemia, accompanied with a recovery of the suppressed IR signal pathway and fasting insulin levels. However, the fasting levels of serum adiponectin and glucagon were lower than that of the control mice, which would remain a potential risk inducing the disruption of glucose homeostasis.
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Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Administración Oral , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Glucagón/sangre , Hormonas/sangre , Insulina/metabolismo , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos de Trialquiltina/administración & dosificaciónRESUMEN
The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single-cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor-intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over-expression suppresses the tumor-intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA-MAVS-IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti-PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV-MAVS-IFN axis.
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Anoikis, a form of apoptotic cell death resulting from inadequate cell-matrix interactions, has been implicated in tumor progression by regulating tumor angiogenesis and metastasis. However, the potential roles of anoikis-related long non-coding RNAs (arlncRNAs) in the tumor microenvironment are not well understood. In this study, five candidate lncRNAs were screened through least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis based on differentially expressed lncRNAs associated with anoikis-related genes (ARGs) from TCGA and GSE40595 datasets. The prognostic accuracy of the risk model was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) analyses revealed significant differences in immune-related hallmarks and signal transduction pathways between the high-risk and low-risk groups. Additionally, immune infiltrate analysis showed significant differences in the distribution of macrophages M2, follicular T helper cells, plasma cells, and neutrophils between the two risk groups. Lastly, silencing the expression of PRR34_AS1 and SPAG5_AS1 significantly increased anoikis-induced cell death in ovarian cancer cells. In conclusion, our study constructed a risk model that can predict clinicopathological features, tumor microenvironment characteristics, and prognosis of ovarian cancer patients. The immune-related pathways identified in this study may offer new treatment strategies for ovarian cancer.
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Neoplasias Ováricas , ARN Largo no Codificante , Humanos , Femenino , Anoicis/genética , Pronóstico , ARN Largo no Codificante/genética , Neoplasias Ováricas/genética , Microambiente Tumoral/genética , Proteínas de Ciclo CelularRESUMEN
Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.
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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019. IMPORTANCE: The outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.
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COVID-19 , Exosomas , Humanos , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Exosomas/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Antivirales/farmacología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Unión ProteicaRESUMEN
Acute myeloid leukemia (AML) is caused by clonal disorders of hematopoietic stem cells. Differentiation therapy is emerging as an important treatment modality for leukemia, given its less toxicity and wider applicable population, but the arsenal of differentiation-inducing agents is still very limited. In this study, we adapted a competitive peptide phage display platform to search for candidate peptides that could functionally induce human leukemia cell differentiation. A monoclonal phage (P6) and the corresponding peptide (pep-P6) were identified. Both L- and D-chirality of pep-P6 showed potent efficiency in inducing AML cell line differentiation, driving their morphologic maturation and upregulating the expression of macrophage markers and cytokines, including CD11b, CD14, IL-6, IL-1ß, and TNF-α. In the THP-1 xenograft animal model, administration of D-pep-P6 was effective in inhibiting disease progression. Importantly, exposure to D-pep-P6 induced the differentiation of primary human leukemia cells isolated AML patients in a similar manner to the AML cell lines. Further mechanism study suggested that D-pep-P6 induced human leukemia cell differentiation by directly activating a TLR-2 signaling pathway. These findings identify a novel D-peptide that may promote leukemia differentiation therapy.
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2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti-inflammatory and hepatoprotective activities. Ultra-performance LC-quadrupole TOF-MS with MS Elevated Energy data collection technique and rapid resolution LC with diode array detection and ESI multistage MS(n) methods were developed for the pharmacokinetics, tissue distribution, metabolism, and excretion studies of THSG in rats following a single intravenous or oral dose. The three metabolites were identified by rapid resolution LC-MS(n). The concentrations of the THSG in rat plasma, bile, urine, feces, or tissue samples were determined by ultra-performance LC-MS. The results showed that THSG was rapidly distributed and eliminated from rat plasma. After the intravenous administration, THSG was mainly distributing in the liver, heart, and lung. For the rat, the major distribution tissues after oral administration were heart, kidney, liver, and lung. There was no long-term storage of THSG in rat tissues. Total recoveries of THSG within 24 h were low (0.1% in bile, 0.007% in urine, and 0.063% in feces) and THSG was excreted mainly in the forms of metabolites, which may resulted from biotransformation in the liver.
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Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacocinética , Glucósidos/farmacocinética , Espectrometría de Masas/métodos , Estilbenos/farmacocinética , Animales , Bilis/química , Medicamentos Herbarios Chinos/análisis , Heces/química , Glucósidos/sangre , Glucósidos/orina , Masculino , Ratas , Ratas Sprague-Dawley , Estilbenos/sangre , Estilbenos/orina , Distribución TisularRESUMEN
The surface layer of the sclerotia of Poria cocos, named Fu-Ling-Pi, is used as a diuretic in traditional Chinese medicine to treat edema and urinary dysfunction. Recent studies have showed that the triterpenes (lanostane and 3,4-secolanostane skeletons) and polysaccharides (beta-pachyman) are the main components of Fu-Ling-Pi and they exhibited various biological activities, such as anti-tumor, antibacterial and antioxidant, etc. This review was focused on the chemistry, pharmacology, and clinical uses of this drug and it may provide scientific foundation for further development and utilization of Fulingpi.
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Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Poria/química , Animales , Quimioterapia , Humanos , Estructura Molecular , WolfiporiaRESUMEN
Because of the rapid mutation and high airborne transmission of SARS-CoV-2, a universal vaccine preventing the infection in the upper respiratory tract is particularly urgent. Here, a mosaic receptor-binding domain (RBD) nanoparticle (NP) vaccine is developed, which induces more RBD-targeted type IV neutralizing antibodies (NAbs) and exhibits broad cross-protective activity against multiple SARS-CoV-2 sublineages including the newly-emerged BF.7, BQ.1, XBB. As several T-cell-reactive epitopes, which are highly conserved in sarbecoviruses, are displayed on the NP surface, it also provokes potent and cross-reactive cellular immune responses in the respiratory tissue. Through intranasal delivery, it elicits robust mucosal immune responses and full protection without any adjuvants. Therefore, this intranasal mosaic NP vaccine can be further developed as a pan-sarbecovirus vaccine to block the viral entrance from the upper respiratory tract.
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COVID-19 , Nanopartículas , Vacunas , Humanos , SARS-CoV-2 , COVID-19/prevención & control , Inmunidad MucosaRESUMEN
The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.
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COVID-19 , Nanopartículas , Animales , Anticuerpos ampliamente neutralizantes , COVID-19/prevención & control , Macaca mulatta/metabolismo , Ratones , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas ConjugadasRESUMEN
Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been shown to be related to the occurrence of type 2 diabetes mellitus (T2DM). Nevertheless, it is necessary to further explore the development of T2DM caused by PCBs and its underlying mechanisms. In the present study, 21-day-old C57BL/6 male mice were orally treated with Aroclor 1254 (0.5, 5, 50 or 500⯵gâ¯kg-1) once every three days. After exposure for 66â¯d, the mice showed impaired glucose tolerance, 13% and 14% increased fasting serum insulin levels (FSIL), and 63% and 69% increases of the pancreatic ß-cell mass in the 50 and 500⯵gâ¯kg-1 groups, respectively. After stopping exposure for 90â¯d, treated mice returned to normoglycemia and normal FSIL. After re-exposure of these recovered mice to Aroclor 1254 for 30â¯d, fasting plasma glucose showed 15%, 28% and 16% increase in the 5, 50 and 500⯵gâ¯kg-1 treatments, FSIL exhibited 35%, 27%, 30% and 32% decrease in the 0.5, 5, 50 or 500⯵gâ¯kg-1 groups respectively, and there was no change in pancreatic ß-cell mass. Transcription of the pancreatic insulin gene (Ins2) was significantly down-regulated in the 50 and 500⯵gâ¯kg-1 groups, while DNA-methylation levels were simultaneously increased in the Ins2 promoter during the course of exposure, recovery and re-exposure. Reduced insulin levels were initially rescued by a compensative increase in ß-cell mass. However, ß-cell mass eventually failed to make sufficient levels of insulin, resulting in significant increases in fasting blood glucose, and indicating the development of T2DM.
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Glucemia/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Homeostasis/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Animales , Glucemia/metabolismo , Metilación de ADN/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Contaminantes Ambientales/administración & dosificación , Insulina/sangre , Insulina/genética , Células Secretoras de Insulina/patología , Masculino , Ratones Endogámicos C57BLRESUMEN
There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration. Additionally, BaP increased amyloid ß protein and cell apoptosis in the adult zebrafish brain. Further, DNA methyltransferase 1 (DNMT1) and DNMT3a were up-regulated in 96 hpf larvae and the adult brain. MeDIP-sequencing data of the 96 hpf larvae identified 235 differentially methylated genes in promoter, with the fold change > 1.5. Guanylate cyclase 2F (gucy2f) and dopamine receptor D4 related sequence (drd4-rs) were hypermethylation promoters, whereas zinc finger C4H2 domain (zc4h2) was a hypomethylation promoter in 96 hpf larvae and the adult brain. The mRNA levels of gucy2f and drd4-rs were down-regulated, and zc4h2 was up-regulated. Our findings suggested that the lasting modifications of DNA methylation were associated with neurodegenerative syndromes in adult zebrafish as a result of early-life BaP exposure.
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Benzo(a)pireno/toxicidad , Enfermedades Neurodegenerativas/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Pez Cebra/embriología , Péptidos beta-Amiloides/metabolismo , Animales , Apoptosis/efectos de los fármacos , Encéfalo/citología , Encéfalo/efectos de los fármacos , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales , Femenino , Locomoción/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neurotransmisores/metabolismo , Fragmentos de Péptidos/metabolismo , Embarazo , ARN Mensajero/metabolismoRESUMEN
Growing evidence indicates that there is an emerging link between environmental pollution and cardiac hypertrophy, while the mechanism is unclear. The objective of this study was to examine whether phenanthrene (Phe) could cause cardiac hypertrophy, and elucidate the molecular mechanisms involved. We found that: 1) Phe exposure increased the heart weight and cardiomyocyte size of rats; 2) Phe exposure led to enlarged cell size, and increased protein synthesis in H9C2 cells; 3) Phe exposure induced important markers of cardiac hypertrophy, such as atrial natriuretic peptide, B-type natriuretic peptide, and c-Myc in H9C2 cells and rat hearts; 4) Phe exposure perturbed miR-133a, CdC42 and RhoA, which were key regulators of cardiac hypertrophy, in H9C2 cells and rat hearts; 5) Phe exposure induced DNA methyltransferases (DNMTs) in H9C2 cells and rat hearts; 6) Phe exposure led to methylation of CpG sites within the miR-133a locus and reduced miR-133a expression in H9C2 cells; 7) DNMT inhibition and miR-133a overexpression could both alleviate the enlargement of cell size and perturbation of CdC42 and RhoA caused by Phe exposure. These results indicated that Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation.
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Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Metilación de ADN/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , MicroARNs/biosíntesis , Miocitos Cardíacos/metabolismo , Fenantrenos/toxicidad , Animales , Cardiomegalia/patología , Línea Celular , Islas de CpG , Masculino , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To examine the expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and CD34 in gastric adenocarcinoma, and to investigate their relations with clinical pathology-related factors. METHODS: Immunohistochemistry (IHC) was used to analyze the expression of CEACAM1 and CD34, and micro-vessel density (MVD) marked by CD34 was calculated in 208 cases of human gastric adenocarcinoma and in 56 cases of normal human gastric tissues. RESULTS: There was no expression of CEACAM1 in normal gastric mucosa. However, all of the gastric adenocarcinoma tissues expressed CEACAM1 with cytoplasmic and/or membranous staining. CEACAM1 expression was classified as high and low (137/208 vs. 71/208, 65.9% vs. 34.1%), the CD34-MVD value was significantly different between the two groups (P<0.05). In addition, expressions of CEACAM1 and CD34 were significantly different from gastric adenocarcinoma to normal gastric tissues, respectively (P<0.05). High CEACAM1 expression and high MVD value were positively associated with lymph nodes metastasis and TNM stage, but negatively related to pathological grade (P<0.05). But they were irrelevant with tumor size, patients' age and gender (P>0.05). CONCLUSIONS: The up-regulation of CEACAM1 expression may participate in tumorous angiogenesis, especially high expression of CEACAM1 promoted its capability of invasion and metastasis.
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Adenocarcinoma/metabolismo , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Mucosa Gástrica/metabolismo , Neovascularización Patológica/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Femenino , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Neoplasias Gástricas/patología , Regulación hacia ArribaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known traditional East-Asian medicinal fungus. the epidermis ("Fu-Ling-Pi" in Chinese) of the sclerotia is used as a diuretic. This study was conducted to evaluate of ethanol extract (EE) and aqueous extract (AE) of the diuretic activity of Fu-Ling-Pi in saline-loaded rats. MATERIAL AND METHODS: The EE and AE were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: Urinary excretion rates were significantly increased by the EE. The three doses of AE only produced a slight increase urinary output. The EE had little or no effect on K(+) excretion, but did indeed induce a notable excretion of Na(+), that was in agreement with the urinary excretion. The three doses of AE produced an increase Na(+) and K(+) excretion, but did not arrive at statistical significance. CONCLUSIONS: The present study confirmed that the not aqueous but ethanol extracts of the epidermis of Poria cocos presents a remarkable diuretic effect.