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1.
Biochem Biophys Res Commun ; 706: 149766, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38484568

RESUMO

Secretory myeloid-derived growth factor (MYDGF) exerts beneficial effects on organ repair, probably via a plasma membrane receptor; however, the identity of the expected receptor has remained elusive. In a recent study, MYDGF was reported as an agonist of the sphingosine-1-phosphate receptor 2 (S1PR2), an A-class G protein-coupled receptor that mediates the functions of the signaling lipid, sphingosine-1-phosphate (S1P). In the present study, we conducted living cell-based functional assays to test whether S1PR2 is a receptor for MYDGF. In the NanoLuc Binary Technology (NanoBiT)-based ß-arrestin recruitment assay and the cAMP-response element (CRE)-controlled NanoLuc reporter assay, S1P could efficiently activate human S1PR2 overexpressed in human embryonic kidney (HEK) 293T cells; however, recombinant human MYDGF, overexpressed either from Escherichia coli or HEK293 cells, had no detectable effect. Thus, the results demonstrated that human MYDGF is not a ligand of human S1PR2. Considering the high conservation of MYDGF and S1PR2 in evolution, MYDGF is also probably not a ligand of S1PR2 in other vertebrates.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Receptores de Lisoesfingolipídeo , Esfingosina/análogos & derivados , Animais , Humanos , Receptores de Esfingosina-1-Fosfato , Receptores de Lisoesfingolipídeo/genética , Receptores de Lisoesfingolipídeo/metabolismo , Ligantes , Células HEK293 , Lisofosfolipídeos/farmacologia
2.
BMC Cancer ; 24(1): 88, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38229045

RESUMO

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Exenteração Pélvica , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/etiologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/etiologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/etiologia
3.
Nanotechnology ; 35(40)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38964289

RESUMO

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Edição de Genes/métodos , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Animais
4.
Ecotoxicol Environ Saf ; 272: 116085, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38342010

RESUMO

Zearalenone (ZEN) is a prevalent mycotoxin that severely impacts human and animal health. However, the possible interactions between ZEN exposure, pathogen infection, immune system, and reactive oxygen species (ROS) were rarely investigated. We studied the effects of early-life ZEN (50 µM) exposure on the immune response of Caenorhabditis elegans against Bacillus thuringiensis infection and the associated mechanisms. The transcriptomic responses of C. elegans after early-life ZEN exposure were investigated using RNA sequencing and followed by verification using quantitative PCR analysis. We also investigated the immune responses of the worms through B. thuringiensis killing assays and by measuring oxidative stress. The transcriptomics result showed that early-life exposure to ZEN resulted in 44 differentially expressed genes, 7 of which were protein-coding genes with unknown functions. The Gene Ontology analysis suggested that metabolic processes and immune response were among the most significantly enriched biological processes, and the KEGG analysis suggested that lysosomes and metabolic pathways were the most significantly enriched pathways. The ZEN-exposed worms exhibited significantly reduced survival after 24-h B. thuringiensis infection, reaching near 100% mortality compared to 60% of the controls. Using qRT-PCR assay, we found that ZEN further enhanced the expression of immunity genes lys-6, spp-1, and clec-60 after B. thuringiensis infection. A concurrently enhanced ROS accumulation was also observed for ZEN-exposed worms after B. thuringiensis infection, which was 1.2-fold compared with the controls. Moreover, ZEN exposure further enhanced mRNA expression of catalases (ctl-1 and ctl-2) and increased catalase protein activity after B. thuringiensis exposure compared with their non-exposed counterparts, suggesting an elevated oxidative stress. This study suggests that early-life exposure to mycotoxin zearalenone overstimulates immune responses involving spp-17, clec-52, and clec-56, resulting in excessive ROS production, enhanced oxidative stress as indicated by aggravated ctl expression and activity, and a decline in host resistance to pathogenic infection which ultimately leads to increased mortality under B. thuringiensis infection. Our findings provide evidence that could improve our understanding on the potential interactions between mycotoxin zearalenone and pathogens.


Assuntos
Bacillus thuringiensis , Micotoxinas , Zearalenona , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Zearalenona/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Micotoxinas/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Imunidade
5.
Plant Dis ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506905

RESUMO

The occurrence of rust fungi on Corydalis bungeana Turcz. and Salix babylonica L. were found in same area of Hebei Province, China from 2022 to 2023. The life cycle connection of these rust fungi was suspected because Peng et al. (2022) reported the life cycle of Melampsora ferrinii Toome & Aime by inoculations, producing spermogonia and aecia on Corydalis species, and uredinia on S. babylonica. The morphology of the uredinial and telial stages on S. babylonica collected in the field was identical with the description of M. ferrinii by Toome and Aime (2015), and its identity was confirmed by phylogenetic analyses using the method of Ji et al. (2020) (LSU-PP087777, ITS-PP091274; Similarity with M. ferrinii: LSU-100%, ITS-99.85%). To confirm the life cycle of this rust fungus, inoculations were conducted on C. bungeana with basidiospores obtained from the teliospores on fallen leaves of Salix babylonica. The fallen leaves producing basidiospores were cut into small pieces (ca. 5 mm2) and placed on healthy leaves of C. bungeana. The inoculated plants were kept in a moist plastic box in darkness at 15-20℃ for 2 days and then transferred to the floor near windows at about 15-20℃ for observations. Ten days after inoculations small yellow spots of spermogonia appeared on the upper surface of the leaves of C. bungeana. About 7 days later, pale yellow aecia with aeciospores were produced mainly on the under surface of the leaves and petioles. The morphology of rust fungus on C. bungeana collected from the fields and obtained by inoculations was identical with the description by Peng et al. (2022). Phylogenetic analyses also showed that a specimen on C. bungeana collected from the field (LSU-OR607838, ITS-OR612063) were included into the same clade of M. ferrinii (Similarity: LSU-100 %, ITS-99.85). Based on morphology, inoculations and DNA sequence analyses, the rust fungi on C. bungeana and S. babylonica are identified as different stages of life cycle of M. ferrinii. This rust fungus has been reported to produce spermogonia and aecia on C. acuminata Franch., C. edulis Maxim. and C. racemosa (Thunb.) Pers. in China (Peng et al. 2022), and uredinia and telia on S. babylonica in USA, Argentina and Iran (Toome and Aime 2015, Abbasi et al. 2024), and on Salix sp. in Chile (Zapata 2016). Therefore, C. bungeana is a new host for M. ferrinii, and its field occurrence on S. babylonica is reported for the first time in China although Peng et al. (2022) reported successful results in its inoculations to S. babylonica in China. This report contributes to the control of rust diseases caused by this species. Specimens used in this experiment were deposited in the Fungal Herbarium of the Jilin Agricultural University, Changchun, China (HMJAU) and sequences newly analyzed were deposited in GenBank.

6.
Biochem Biophys Res Commun ; 679: 110-115, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37677979

RESUMO

The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin. Do fish GHSRs use another peptide as their agonist? In the present study we tested to two fish motilins from D. rerio and L. chalumnae because motilin is distantly related to ghrelin. In ligand binding and activation assays, the fish GHSRs from D. rerio and L. crocea displayed no detectable or very low binding to all tested motilins; however, the fish GHSR from L. chalumnae bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR in the ray-finned fish D. rerio and L. crocea, but is an efficient agonist for GHSR in the lobe-finned fish L. chalumnae, one of the closest fish relatives of tetrapods. The results of present study suggested that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins.

7.
Acta Pharmacol Sin ; 44(11): 2322-2330, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37328649

RESUMO

Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide  additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.


Assuntos
Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Leucócitos Mononucleares/metabolismo , Anticorpos Monoclonais , Imunoglobulina G/metabolismo
8.
Nutr J ; 22(1): 17, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36918892

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability among older adults. Medical and surgical treatments are costly and associated with side effects. A natural nutraceutical, collagen hydrolysate, has received considerable attention due to its relieving effects on OA-associated symptoms. This study investigated the effects of hydrolyzed collagen type II (HC-II) and essence of chicken (BRAND'S Essence of Chicken) with added HC-II (EC-HC-II) on joint, muscle, and bone functions among older adults with OA. METHODS: Patients (n = 160) with grade 1-3 knee OA according to the Kellgren-Lawrence classification system, joint pain for ≥ 3 months, and a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of > 6 were randomly assigned with equal probability to consume EC-HC-II, HC-II, glucosamine HCl, or a placebo for 24 weeks in combination with resistance training. Outcome measurements were WOMAC score, visual analogue scale (VAS) pain score, grip strength, fat-free mass (FFM), and bone mass. RESULTS: All groups exhibited similar levels of improvement in WOMAC index scores after 24 weeks. HC-II significantly reduced VAS pain score by 0.9 ± 1.89 (p = 0.034) after 14 days. A repeated-measures analysis of variance showed that HC-II reduced pain levels more than the placebo did (mean ± standard error: - 1.3 ± 0.45, p = 0.021) after 14 days; the EC-HC-II group also had significantly higher FFM than the glucosamine HCl (p = 0.02) and placebo (p = 0.017) groups and significantly higher grip strength than the glucosamine HCl group (p = 0.002) at 24 weeks. CONCLUSION: HC-II reduces pain, and EC-HC-II may improve FFM and muscle strength. This suggests that EC-HC-II may be a novel holistic solution for mobility by improving joint, muscle, and bone health among older adults. Large-scale studies should be conducted to validate these findings. TRIAL REGISTRATION: This trial was retrospectively registered at ClinicalTrials.gov (NCT04483024).


Assuntos
Galinhas , Osteoartrite do Joelho , Animais , Humanos , Colágeno Tipo II/uso terapêutico , Projetos Piloto , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/tratamento farmacológico , Dor/complicações , Dor/tratamento farmacológico , Glucosamina/uso terapêutico , Músculos , Método Duplo-Cego , Resultado do Tratamento
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(1): 33-37, 2023 Feb.
Artigo em Zh | MEDLINE | ID: mdl-36861152

RESUMO

Objective To observe the effect of calcified lymph nodes on video-assisted thoracoscopic surgery (VATS) lobectomy in the chronic obstructive pulmonary disease (COPD) patients with lung cancer. Methods A retrospective analysis was conducted on the COPD patients with lung cancer who underwent VATS lobectomy in the Department of Thoracic Surgery in the First Affiliated Hospital of Hebei North University from May 2014 to May 2018.The patients were assigned into a calcified lymph node group and a control group according to the presence or absence of calcified lymph nodes in CT,and the size,morphology,and calcification degree of the lymph nodes were recorded.The operation duration,intraoperative blood loss,chest tube retention time,hospitalization days,and overall complication rate were compared between the two groups. Results The 30 patients in the calcified lymph node group included 17 patients with one calcified lymph node and 13 patients with two or more calcified lymph nodes,and a total of 65 calcified lymph nodes were recorded.The calcified lymph nodes with the size ≤5 mm were the most common (53.8%),and complete calcification was the most common form (55.4%) in lymph node calcification.The mean operation duration had no significant difference between the calcified lymph node group and the control group (t=-1.357,P=0.180).The intraoperative blood loss (t=-2.646,P=0.010),chest tube retention time (t=-2.302,P=0.025),and hospitalization days (t=-2.274,P=0.027) in the calcified lymph node group were higher than those in the control group. Conclusion Calcified lymph nodes increase the difficulty and risk of VATS lobectomy in the COPD patients with lung cancer.The findings of this study are conducive to predicting the perioperative process of VATS lobectomy.


Assuntos
Calcinose , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Humanos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Linfonodos
10.
J Environ Sci (China) ; 117: 141-150, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35725066

RESUMO

UV/peroxymonosulfate (UV/PMS) advanced oxidation process has attracted significant attention for removal of micropollutants in water. However, during practical water treatment applications, the PMS treatment must be performed before the UV treatment to achieve full contact. In this study, sulfamethoxazole (SMX) was selected as the target micropollutant. Four different operational approaches, including UV alone, PMS alone, simultaneous UV/PMS and sequential PMS-UV, were compared for their differences in SMX removal and disinfection by-product (DBP) formation potentials during chlorine-driven disinfection. Among the four approaches, UV/PMS and PMS-UV achieved over 90% removal efficiencies for SMX without substantial differences. For raw water, the trichloronitromethane (TCNM) formation potential after treatment with PMS-UV was lower than that after UV/PMS treatment. The time interval over which the PMS-UV process was conducted had little effect on the final removal efficiency for SMX. However, a brief (5 min) pre-PMS treatment significantly reduced the TCNM formation potential and the genotoxicity from DBPs. The formation risk for TCNM during chlorination increased markedly with increasing PMS dosages, and the appropriate dosage under these experimental conditions was suggested to be 0.5-1.0 mmol/L. Under alkaline conditions, PMS-UV treatment can enhance SMX degradation as well as dramatically reduced the formation potentials for haloketones, haloacetonitriles and halonitromethanes. This study suggests that proper optimization of UV/PMS processes can remove SMX and reduce its DBP formation.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Cloro , Desinfecção , Halogenação , Peróxidos , Sulfametoxazol , Poluentes Químicos da Água/análise
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 682-687, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-35871741

RESUMO

Objective: To explore the risk factors of abdominal aortic enlargement (AAE) after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford type B aortic dissection. Methods: The clinical and imaging data of patients who underwent TEVAR-TSI for Stanford type B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through September 2020 were retrospectively collected and analyzed. CT angiography (CTA) scans were performed before the procedure. Follow-up CTA scans were scheduled and performed in 1, 3, 6, and 12 months after the procedure and annually thereafter. The primary outcome was AAE. The risk factors of AAE after TEVAR-TSI were selected and survival analysis and multivariate logistic regression were conducted accordingly. Results: A total of 146 patients were regularly followed up at our hospital, with the median followup time of the entire cohort being 48 months (ranging from 12 to 84 months). During the followup period after TEVAR-TSI, the incidence of AAE was 19.9% (29/146). A total of 29 patients developed AAE (the AAE group), while 117 patients did not develop AAE (the non-AAE group). There were a total of 27 deaths, including 13 in the non-AAE group versus 14 in the AAE group. Distal aortic reoperation was performed on 10 patients, including 4 in the non-AAE group versus 6 in the AAE group. The cumulative long-term survival and freedom from distal aortic reoperation of the non-AAE group were both significantly better those of the AAE group ( P<0.05). Logistic multivariate regression analysis showed that independent risk factors of AAE after TEVAR-TSI included the following, partial thrombosis of the false lumen (odds ratio [ OR]=4.090, 95% confidence interval [ CI]: 1.539-10.867, P=0.005), the longer cumulative diameter of residual intimal tear above the level of the lowest renal arteries ( OR=1.290, 95% CI: 1.164-1.429, P=0.000), and shorter cumulative diameter of residual intimal tear below the level of the lowest renal arteries ( OR=0.487, 95% CI: 0.270-0.878, P=0.017). Conclusion: The prognosis of patients who developed AAE after TEVAR-TSI was not good. During followup visits, as precautions against the development of AAE, close attention should be paid to partial thrombosis of the false lumen, cumulative diameter of residual intimal tear above the level of the lowest renal arteries, and cumulative diameter of residual intimal tear below the level of the lowest renal arteries.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Trombose , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Análise Fatorial , Humanos , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Trombose/etiologia , Trombose/cirurgia , Resultado do Tratamento
12.
Virus Genes ; 57(2): 194-204, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33559837

RESUMO

The structural protein VP3 of infectious bursal disease virus (IBDV) plays a critical role in viral assembly, replication, immune escape, and anti-apoptosis. Interaction between VP3 and host protein factors can affect stages in the viral replication cycle. In this study, 137 host proteins interacting with VP3 protein were screened through liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics approach. The functions and relevance of the proteins were obtained through bioinformatics analysis. Most VP3-interacting proteins were linked to binding, catalytic activity, and structural molecular activity, and performed functions in cell parts and cells. Biological functions of VP3-interacting proteins were mainly relevant to "Cytoskeleton", "Translation", and "Signal transduction mechanisms", involving ribosomes, "Tight junction", regulation of actin cytoskeleton, and other pathways. Six potential VP3-interacting proteins in host cells were knocked down, and vimentin, myosin-9, and annexin A2 were found to be related to IBDV replication. This study would help explore regulatory pathways and cellular mechanisms in IBDV-infected cells, and also provided clues for the in-depth study of VP3 biological functions and IBDV replication or pathogenesis.


Assuntos
Vírus da Doença Infecciosa da Bursa/metabolismo , Proteínas Estruturais Virais/metabolismo , Animais , Linhagem Celular , Embrião de Galinha , Cromatografia Líquida , Fibroblastos/virologia , Ligação Proteica , Mapas de Interação de Proteínas , Proteínas/metabolismo , Proteoma/metabolismo , Espectrometria de Massas em Tandem , Replicação Viral
13.
Int J Neurosci ; 131(9): 854-863, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32419569

RESUMO

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated, autoimmune neuromuscular disease. Reports have indicated that the CD28/B7 ligand interactions play a crucial role during primary immune responses. Hence, the aim of the present study was to investigate the possible effects of the CD28/B7 pathway on the occurrence and development of MG and its associated cytokine factors. METHODS: An experimental autoimmune myasthenia gravis (EAMG) was initially established by immunization of Lewis rats with acetylcholine receptor (AChR) α97-116 peptide. Then the rats were treated with dexamethasone and CTLA4-Ig (used for inhibiting the CD28/B7 pathway). Serum levels of AChR IgG and AChR IgG2b were then detected using ELISA. The clinical features, muscle contraction function, AChR content, expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood and the secretion of cytokines (INF-γ, IL-2, IL-10 and IL-12) in serum of rats were measured. Finally, lymphocyte proliferation upon CTLA4 IgG treatment was examined in vitro. RESULTS: Inhibition of the CD28/B7 pathway and dexamethasone were found to significantly improve clinical symptoms of EAMG rats, reduce serum levels of AChR IgG, AChR IgG2b, INF-γ, IL-2, IL-10 and IL-12, the expression of CD28, CTLA4, B7.1 and B7.2 in mononuclear cells of peripheral blood, and enhance muscle contraction function and AChR content in the muscle in vivo. Meanwhile, CTLA4 IgG could abolish the increased lymphocyte proliferation following AChR stimulation in vitro. CONCLUSION: Overall, the suppression of the CD28/B7 pathway by CTLA4-Ig can have the potential to retard the occurrence and development of MG.


Assuntos
Citocinas/metabolismo , Miastenia Gravis/metabolismo , Transdução de Sinais , Animais , Antígenos B7/metabolismo , Antígenos CD28/metabolismo , Feminino , Linfócitos/metabolismo , Ratos Endogâmicos Lew
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 111-116, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33474899

RESUMO

OBJECTIVE: To investigate the characteristics of aortic remodeling after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford B aortic dissection. METHODS: The clinical and imaging data of 128 patients who underwent TEVAR-TSI for Stanford B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through May 2019 were retrospectively collected. CT images were obtained before (T 0) TEVAR-TSI and, 1 week (T 1), 3 months (T 2), 6 months (T 3), 1 year (T 4) after TEVAR-TSI. The maximum diameter of the true lumen and false lumen in the short axis view was accessed at five levels: L 1: the level of primary tear entry, L 2: the level of the bronchial bifurcation, L 3: the level of the distal of the first stent-graft, L 4: the level of the celiac trunk, L 5: the level of the lowest renal arteries. The false lumen thrombosis in the thoracic aorta and abdominal aorta were assessed at different times, the false lumen and true lumen changes in diameter were evaluated between the preoperative and postoperative CT scan. RESULTS: The stented segment of the descending thoracic aorta was evaluated (L 1-L 3): The true lumen diameter showed an increasing trend and the false lumen diameter showed an decreasing trend at levels L 1, L 2, and L 3, the change of true lumen diameter was positively correlated with the follow-up time ( r=0.721, 0.827, 0.893, P<0.05), and the change rate of true lumen diameter was positively correlated with the follow-up time ( r=0.763, 0.818, 0.902, P<0.05), and the change of false lumen diameter was negatively correlated with the follow-up time ( r=-0.750, -0.927, -0.934, P<0.05), and the change rate of false lumen diameter was negatively correlated with the follow-up time (-0.774, -0.935, -0.952, P<0.05). When the unstented segment of the abdominal aorta was evaluated (L 4-L 5), the average true lumen diameter at the level of celiac trunk increased significantly at 1 year by 13.7% ( P=0.007), however, the average false lumen diameter did not change over time ( P=0.406). The average true lumen diameter and false lumen diameter at the level of the lowest renal arteries increased over time as well, the average true lumen increased by 10.1%, and the average false lumen increased by 13.6% ( P=0.048, 0.017). Besides, the complete false lumen thrombosis rate of the stented segment of the descending thoracic aorta was higher than that of the unstented segment of the abdominal aorta.e complete false lumen thrombosis rate of the stented segment of the descending thoracic aorta was higher than that of the unstented segment of the abdominal aorta. CONCLUSION: After receiving TEVAR-TSI, Stanford type B aortic dissection patients had high thrombosis absorption rate in the thoracic aortic segment covered by stent, and the aortic remodeling was more ideal. The aortic remodeling effect in the abdominal aortic segment not covered was not ideal, and the inner diameter of the abdominal aorta tended to increase. Therefore, close follow-up monitoring should be conducted.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Humanos , Estudos Retrospectivos , Stents , Resultado do Tratamento
15.
J Vasc Interv Radiol ; 30(3): 401-409.e2, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819483

RESUMO

PURPOSE: Can focal laser ablation (FLA) of low to intermediate risk prostate cancer preserve sexual and urinary function with low morbidity while providing adequate oncologic outcomes. MATERIALS AND METHODS: Transrectal FLA was done in 120 patients with low- to intermediate-risk prostate cancer. MR imaging thermometry controlled ablation. At 6 and 12 months, patients had clinical and MR imaging follow-up with biopsy of suspicious areas. Patients submitted surveys of sexual and urinary function. Multivariate logistic regression identified determinants of positive imaging and biopsies. Two-sided Wilcoxon signed rank test evaluated scores and laboratory values. RESULTS: Median patient age was 64 years, and median prostate-specific antigen (PSA) was 6.05 ng/mL. Median follow-up period was 34 months (range, 17-55 months). Gleason score was 3+3=6 in 37 (30.8%), 3+4=7 in 56 (46.7%), and 4+3=7 in 27 (22.5%) patients. Tumor stage was T1c in 89 (74.2%), T2a in 26 (21.7%), and T2b in 5 (4.2%) patients. Twenty (17%) patients had additional oncologic therapy 1 year after FLA when biopsy confirmed cancer following abnormal MR imaging. There was no difference between functional scores before and after ablation. Median PSA decreased to 3.25 at 12 months (P < .001). Tumor diameter above the median (odds ratio = 3.36; 95% confidence interval, 1.41-7.97) was the only significant predictor for positive MR imaging after treatment. CONCLUSIONS: One year after FLA, selected patients had low morbidity, no significant changes in quality of life, and 83% freedom of retreatment rate. Sexual and urinary function did not significantly change after FLA.


Assuntos
Terapia a Laser/métodos , Neoplasias da Próstata/cirurgia , Biópsia , Humanos , Calicreínas/sangue , Terapia a Laser/efeitos adversos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Qualidade de Vida , Medição de Risco , Fatores de Risco , Comportamento Sexual , Disfunções Sexuais Fisiológicas/etiologia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Transtornos Urinários/etiologia
16.
Exp Cell Res ; 370(2): 506-518, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30031130

RESUMO

Ischemia/reperfusion (I/R) injury, one of the leading health problems in the world, is defined as a cause of cardiomyocytes death. In the present study, we investigate the role of formyl peptide receptor 1 (FPR1) in cardiomyocyte apoptosis and ventricular remodeling of I/R injury rats and the underlying mechanism involving mitogen-activated protein kinase (MAPK) signaling pathway. The important differentially expressed genes (DEGs) in I/R injury were screened out and downstream pathways affected by DEGs were predicted. We grouped 90 rats into sham, I/R, NC siRNA, FRP1 siRNA, empty vector, and FRP1 vector groups and established a model of I/R injury in rats. CVF value, myocardial infarct areas and positive expression rate of FPR1 and MAPK were detected. Levels of FPR1 and MAPK pathway-related genes were determined by RT-qPCR and western blot analysis. MTT assay was performed to evaluate cell proliferation and flow cytometry to evaluate cell cycle progression and apoptosis. GSE19804 and GSE27262 were screened from Gene Expression Omnibus database. FPR1 was higher in patients with I/R injury and activate the MAPK signaling pathway. FRP1 gene silencing decreased CVF value, infarct area, apoptotic index, positive expression rates of FPR1 and MAPK, decreased FPR1, p38, ERK, JNK, MMP-2, TIMP-2, NF-kB, Bax, p-p38, p-ERK, and p-JNK levels, increased Bcl-2 level, promoted cell proliferation and cell cycle progression, and inhibited cell apoptosis rate. Overall, our study demonstrates that the silencing of FPR1 gene depresses inflammation, cardiomyocyte apoptosis and ventricular remodeling in rats with I/R injury through the suppressing the activation of the MAPK signaling pathway.


Assuntos
Apoptose/genética , Miócitos Cardíacos/metabolismo , Receptores de Formil Peptídeo/genética , Traumatismo por Reperfusão/metabolismo , Remodelação Ventricular/fisiologia , Animais , Proliferação de Células/genética , Inativação Gênica/fisiologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Cancer ; 124(15): 3127-3135, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29660813

RESUMO

BACKGROUND: Treatments for muscle-invasive bladder cancer are multimodal, complex, and often carry significant risks of physical and psychological morbidity. The objectives of this study were to define the incidence and types of psychiatric illnesses diagnosed after treatment and to determine their impact on survival outcomes. METHODS: In total, 3709 patients who were diagnosed with clinical stage T2 through T4a bladder cancer from January 1, 2002, to December 31, 2011, from the Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable analysis and Cox proportional-hazards models were used to determine the predictors associated with psychiatric diagnosis and impact on survival outcomes. RESULTS: Of 3709 patients, 1870 (50.4%) were diagnosed with posttreatment psychiatric disorders. Patients who underwent radical cystectomy were identified as being at significantly greater risk of having a posttreatment psychiatric illness compared with those who received radiotherapy and/or chemotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In adjusted analyses, diagnosis of a psychiatric disorder resulted in significantly worse overall survival (HR, 2.80; 95% CI, 2.47-3.17; P < .001) and cancer-specific survival (HR, 2.39; 95% CI, 2.05-2.78; P < .001). CONCLUSIONS: One-half of patients with muscle-invasive bladder cancer who underwent treatment were diagnosed with a psychiatric disorder, which resulted in worse survival outcomes compared with patients who did not have a posttreatment psychiatric diagnosis. This information can be used to inform interventions to educate patients with muscle-invasive bladder cancer regarding the impact of different treatments on mental health. Cancer 2018. © 2018 American Cancer Society.


Assuntos
Transtornos Mentais , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologia , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Medicare , Modelos de Riscos Proporcionais , Programa de SEER , Estados Unidos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/terapia
19.
Environ Microbiol ; 19(6): 2468-2482, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28447395

RESUMO

As an analogue of phosphorus, arsenic (As) has a biogeochemical cycle coupled closely with other key elements on the Earth, such as iron, sulfate and phosphate. It has been documented that microbial genes associated with As biotransformation are widely present in As-rich environments. Nonetheless, their presence in natural environment with low As levels remains unclear. To address this issue, we investigated the abundance levels and diversities of aioA, arrA, arsC and arsM genes in estuarine sediments at low As levels across Southeastern China to uncover biogeographic patterns at a large spatial scale. Unexpectedly, genes involved in As biotransformation were characterized by high abundance and diversity. The functional microbial communities showed a significant decrease in similarity along the geographic distance, with higher turnover rates than taxonomic microbial communities based on the similarities of 16S rRNA genes. Further investigation with niche-based models showed that deterministic processes played primary roles in shaping both functional and taxonomic microbial communities. Temperature, pH, total nitrogen concentration, carbon/nitrogen ratio and ferric iron concentration rather than As content in these sediments were significantly linked to functional microbial communities, while sediment temperature and pH were linked to taxonomic microbial communities. We proposed several possible mechanisms to explain these results.


Assuntos
Arsênio/metabolismo , Bactérias/classificação , Bactérias/metabolismo , Biotransformação/fisiologia , Sedimentos Geológicos/microbiologia , Bactérias/genética , Biotransformação/genética , China , Meio Ambiente , RNA Ribossômico 16S/genética , Áreas Alagadas
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