RESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease caused by the Dabie bandavirus, with a high mortality rate. Currently, there are no effective vaccines or specific treatments for SFTS. Early diagnosis and accurate severity assessment are crucial. METHODS: This study included 171 cases of SFTS, COVID-19, and hepatitis B virus (HBV) patients and healthy controls. We compared the serum adenosine deaminase (ADA) activity across these groups. The diagnostic and prognostic efficiency of serum ADA for SFTS was evaluated by using receiver operating characteristic (ROC) curve analysis. We also examined the correlation between serum ADA in SFTS patients and clinical lab parameters as well as serum cytokines. RESULTS: SFTS patients had significantly higher serum ADA activity than those of COVID-19, HBV patients, and healthy controls. Nonsurvivor SFTS patients had notably higher ADA than survivors. ROC analysis indicated ADA as an effective SFTS diagnostic and prognostic biomarker. ADA correlated with prognosis, viral load, APTT, PT, AST, ferritin, negatively with HDL-c and LDL-c, and positively with cytokines like IL-6, TNF-α, and IL-1ß. Multiorgan failure patients showed significant ADA increase. CONCLUSION: Elevated serum ADA activity in SFTS patients is linked with disease severity and prognosis, showing potential as a diagnostic and prognostic biomarker for SFTS.
RESUMO
To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway.
Assuntos
Injúria Renal Aguda , Polissacarídeos , Selênio , Animais , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Cisplatino/farmacologia , Cisplatino/toxicidade , Rim/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Selênio/farmacologia , Compostos de Organossilício/metabolismo , Compostos de Organossilício/farmacologiaRESUMO
BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease primarily affecting the exocrine glands, which has a variety of clinical manifestations and unclear pathogenic mechanisms. Adenosine deaminase (ADA) is an enzyme involved in the breakdown of purines, and changes in its activity have been associated with a number of autoimmune diseases. This study aims to investigate the relationship between serum ADA activity and disease activity in patients with pSS. METHODS: In this study, 196 patients with pSS and 196 healthy controls were enrolled. Serum ADA activity and clinical laboratory parameters were collected and analyzed in both groups. Pearson correlation analysis was used to examine the correlation between ADA activity and clinical laboratory parameters, as well as the correlation between ADA activity and the disease activity score. RESULTS: Compared with healthy controls, the activity of ADA in the serum of pSS patients was significantly increased (P < 0.0001), and the ADA activity was significantly decreased after immunosuppressive treatment (P < 0.0001). Correlation analysis revealed that the activity of ADA was significantly positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.3, P < 0.0001) and serum immunoglobulin G (IgG) levels (r = 0.5, P < 0.0001), and significantly negatively correlated with high-density lipoprotein (HDL) (r = -0.4, P < 0.0001). Furthermore, there was a significant positive correlation between ADA activity and the disease activity score as measured by the Sjögren's Syndrome Disease Activity Index (SSDAI) (r = 0.4, P < 0.0001). CONCLUSION: This study found that patients with pSS have higher activity of ADA in serum, which is associated with disease activity as measured by SSDAI. These results suggest that ADA activity may be a potential biomarker for evaluating disease activity and treatment efficacy in pSS patients. Additionally, ADA may be a potential target for the treatment of pSS patients.
Assuntos
Doenças Autoimunes , Síndrome de Sjogren , Humanos , Adenosina Desaminase , Biomarcadores , Síndrome de Sjogren/diagnóstico , Resultado do TratamentoRESUMO
Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.
Assuntos
Doenças Autoimunes , Neoplasias , Humanos , Receptor A2A de Adenosina , Adenosina/metabolismo , Adenosina/uso terapêutico , Transdução de Sinais , Neoplasias/tratamento farmacológicoRESUMO
It is still uncertain whether the consumption of Lachnum sp. polysaccharides (LEP) alleviates colorectal cancer (CRC) through the gut microbiota. In this study, our efforts are focused on the influence of LEP on CRC, intestinal barrier and inflammation, and fecal microbiota and the metabolites, in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. Results showed that LEP inhibited CRC mouse colon shortening and weight loss, decreased tumor incidence, restored intestinal barrier integrity, and reduced excessive inflammation. LEP consumption significantly altered microbiota overall structure and community, with reduced pernicious bacteria (such as Parabacteroides, Escherichia_Shigella, Desulfovibrio and Helicobacter), and increased beneficial bacterium (such as Alistipes, Alloprevotella and Ruminiclostridium). Fecal-metabolome profile indicated that a total of 43 metabolites were clearly changed, with 10 down-regulated and 33 up-regulated metabolites. In addition, short-chain fatty acids (SCFAs), including acetic acid, propionic acid and n-butyric acid, were significantly increased after LEP administration. Moreover, a strong correlation between the fluctuant gut microbiota and metabolites was found. These findings provided not only deeper insights into the responsibility of LEP for CRC alleviation, and but also the potential of LEP as a promising candidate for CRC prevention and treatment.
Assuntos
Colite , Microbioma Gastrointestinal , Animais , Bactérias , Carcinogênese , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
This study was designed to investigate the liver and kidney protective efficacy of a Lachnum polysaccharide (LEP) against Pb-induced toxicity in mice. The results showed that LEP decreased the Pb-induced bodyweight loss and organ index. Moreover, biochemical analysis showed that treatment of LEP could improve antioxidant status (CAT, GSH-Px and MDA) and the injury of tissues (liver and kidney). In addition, the histopathological observations indicated that LEP could attenuate liver and kidney cell injury induced by Pb. For further studies, key proteins involved in hepatic and kidney apoptosis, including cleaved caspase-3, Bax, Bcl-2, TGF-ß1 and α-SMA, were quantified. The present findings demonstrated that LEP is strongly effective in protecting against the liver and kidney injury induced by Pb. We hope this research can offer a theoretical base for development of polysaccharide based on nutraceutical food in future.
Assuntos
Ascomicetos/química , Rim/efeitos dos fármacos , Rim/patologia , Intoxicação por Chumbo/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Biomarcadores , Biópsia , Modelos Animais de Doenças , Rim/metabolismo , Testes de Função Renal , Intoxicação por Chumbo/tratamento farmacológico , Intoxicação por Chumbo/metabolismo , Intoxicação por Chumbo/prevenção & controle , Fígado/metabolismo , Testes de Função Hepática , Masculino , Camundongos , Estresse Oxidativo , Polissacarídeos/química , Substâncias Protetoras/químicaRESUMO
PURPOSE: The 21-gene recurrence score (RS) assay predicts relapse of estrogen receptor-positive and lymph node-negative breast cancer more accurately than traditional markers; however, whether this assay can be regarded as a molecular marker of other types of breast cancer is unclear. We aimed to identify the effect of 21-gene recurrence score assay in non-estrogen receptor-positive and lymph node-negative breast cancer. METHODS: We analyzed 21-gene expression by quantitative real-time PCR (qRT-PCR) in 100 cases of breast cancer tissues and followed up for 5 years to investigate the prognostic significance in non-estrogen receptor-positive and lymph node-negative breast cancer. Also, the correlation between RS and the clinicopathological features were analyzed. Adjuvant online (AOL) database was used for the analyses in the present study. RESULTS: The cases were classified as RS low (n=52), moderate (n=22) and high (n=26) risk. The RS based on the21-gene assay was not correlated with age, tumor size, histological grade, and lymph node and estrogen receptor/progesterone receptor (ER/PR) status; however, there was significant correlation with Her-2 status. The 5-year recurrence rates were 1.92%, 4.55% and 15.38% in the low, moderate and high-risk groups, respectively. In addition, there was significant difference between the low-high groups (p<0.05). Furthermore, the consistency of the prognosis predicted by the AOL system was 56% and 59% in the RS moderate-high risk and low risk groups, respectively. CONCLUSIONS: The 21-gene RS assay was a prognostic indicator for patients with non-ER-positive and lymph node-negative breast cancer. In addition, our results coincided with those obtained using the AOL system.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/terapia , Perfilação da Expressão Gênica , Linfonodos/patologia , Recidiva Local de Neoplasia/diagnóstico , Receptores de Estrogênio/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfonodos/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismoRESUMO
The aim of this study was to evaluate the association between thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (SLC19A1) gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in the TS, MTHFR and SLC19A1 genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with the SLC19A1 CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes of MTHFR assessed. The RR was higher in patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5'-UTR of the TS gene and exon 6 (2522) C/T of the SLC19A1 gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.