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1.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860546

RESUMO

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

2.
Sci Rep ; 14(1): 12430, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816541

RESUMO

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.


Assuntos
Corticosterona , Dinoprostona , Epinefrina , Fatores de Crescimento de Fibroblastos , Glucagon , Ácidos Linoleicos Conjugados , Camundongos Transgênicos , Animais , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Camundongos , Ácidos Linoleicos Conjugados/farmacologia , Ácidos Linoleicos Conjugados/metabolismo , Corticosterona/metabolismo , Dinoprostona/metabolismo , Glucagon/metabolismo , Epinefrina/metabolismo , Termogênese/efeitos dos fármacos , Termogênese/genética , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Lipólise/efeitos dos fármacos , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/genética , Adiposidade/efeitos dos fármacos
4.
BMC Infect Dis ; 24(1): 485, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730327

RESUMO

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.


Assuntos
Antibacterianos , Brucelose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Brucelose/tratamento farmacológico , Brucelose/microbiologia , Brucelose/líquido cefalorraquidiano , Brucelose/diagnóstico , Brucelose/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Adolescente , Adulto Jovem , China/epidemiologia , Resultado do Tratamento , Brucella/isolamento & purificação , Animais
5.
J Pharm Anal ; 14(5): 100929, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799234

RESUMO

Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.

6.
Int J Surg ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775550

RESUMO

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

7.
J Dig Dis ; 25(3): 191-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38697920

RESUMO

OBJECTIVE: To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI). METHODS: Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed. RESULTS: The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns. CONCLUSION: BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.


Assuntos
Cárdia , Estudos de Viabilidade , Neoplasias Gástricas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cárdia/patologia , Cárdia/diagnóstico por imagem , Adulto , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Idoso , Pólipos/diagnóstico por imagem , Pólipos/diagnóstico , Gastroscopia/métodos , Sensibilidade e Especificidade , Valor Preditivo dos Testes , Lasers
8.
Diabetes Metab Syndr ; 18(5): 103023, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697002

RESUMO

BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases. METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

9.
Virology ; 595: 110097, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685171

RESUMO

Current influenza vaccine is not effective in providing cross-protection against variants. We evaluated the immunogenicity and efficacy of multi-subtype neuraminidase (NA) and M2 ectodomain virus-like particle (m-cNA-M2e VLP) and chimeric M2e-H3 stalk protein vaccines (M2e-H3 stalk) in ferrets. Our results showed that ferrets with recombinant m-cNA-M2e VLP or M2e-H3 stalk vaccination induced multi-vaccine antigen specific IgG antibodies (M2e, H3 stalk, NA), NA inhibition, antibody-secreting cells, and IFN-γ secreting cell responses. Ferrets immunized with either m-cNA-M2e VLP or M2e-H3 stalk vaccine were protected from H1N1 and H3N2 influenza viruses by lowering viral titers in nasal washes, trachea, and lungs after challenge. Vaccinated ferret antisera conferred broad humoral immunity in naïve mice. Our findings provide evidence that immunity to M2e and HA-stalk or M2e plus multi-subtype NA proteins induces cross-protection in ferrets.


Assuntos
Anticorpos Antivirais , Proteção Cruzada , Furões , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Neuraminidase , Infecções por Orthomyxoviridae , Vacinas de Partículas Semelhantes a Vírus , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Proteção Cruzada/imunologia , Anticorpos Antivirais/imunologia , Neuraminidase/imunologia , Neuraminidase/genética , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Camundongos , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/genética , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas Viroporinas , Proteínas Virais
10.
J Chin Med Assoc ; 87(6): 581-589, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651895

RESUMO

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. METHODS: Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 hour. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. RESULTS: Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. CONCLUSION: This study demonstrated that hyperglycemia upregulates MALAT1 . MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease.


Assuntos
Regulação para Baixo , Exossomos , Glucose , Macrófagos , MicroRNAs , RNA Longo não Codificante , Regulação para Cima , Animais , Masculino , Camundongos , Ratos , Autofagia/efeitos dos fármacos , Células Cultivadas , Exossomos/metabolismo , MicroRNAs/fisiologia , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos Sprague-Dawley , RNA Longo não Codificante/fisiologia , RNA Longo não Codificante/genética
11.
J Asian Nat Prod Res ; : 1-15, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598409

RESUMO

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.

12.
Pestic Biochem Physiol ; 200: 105816, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582574

RESUMO

The melon fly Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agricultural quarantine pest threatening fruit and vegetable production. Heat shock cognate 70 (Hsc70), which is a homolog of the heat shock protein 70 (Hsp70), was first discovered in mice testes and plays an important role in spermatogenesis. In this study, we identified and cloned five Hsc70 genes from melon fly, namely ZcHsc70_1/2/3/4/5. Phylogenetic analysis showed that these proteins are closely related to Hsc70s from other Diptera insects. Spatiotemporal expression analysis showed that ZcHsc70_1 and ZcHsc70_2 are highly expressed in Z. cucurbitae testes. Fluorescence in situ hybridization further demonstrated that ZcHsc70_1 and ZcHsc70_2 are expressed in the transformation and maturation regions of testes, respectively. Moreover, RNA interference-based suppression of ZcHsc70_1 or ZcHsc70_2 resulted in a significant decrease of 74.61% and 63.28% in egg hatchability, respectively. Suppression of ZcHsc70_1 expression delayed the transformation of sperm cells to mature sperms. Meanwhile, suppression of ZcHsc70_2 expression decreased both sperm cells and mature sperms by inhibiting the meiosis of spermatocytes. Our findings show that ZcHsc70_1/2 regulates spermatogenesis and further affects the male fertility in the melon fly, showing potential as targets for pest control in sterile insect technique by genetic manipulation of males.


Assuntos
Sementes , Tephritidae , Masculino , Animais , Camundongos , Filogenia , Hibridização in Situ Fluorescente , Tephritidae/genética , Controle de Insetos/métodos , Espermatogênese/genética , Fertilidade/genética , Resposta ao Choque Térmico
13.
Sci Total Environ ; 927: 172268, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583629

RESUMO

Due to the inappropriate disposal of waste materials containing lead (Pb) and irrigation with sewage containing Pb, the migration of Pb2+ within the soil profile has been extensively investigated. The conventional Pb2+ block method is challenging to implement due to its complex operational procedures and high construction costs. To address this issue, this study introduces the microbial-induced carbonate precipitation (MICP) technique as a novel approach to impede the migration of Pb2+ in the soil profile. Soil acclimatization with urea resulted in an increased proportion of urease-producing microorganisms, including Bacillus, Paenibacillus, and Planococcaceae, along with heightened expression of urea-hydrolyzing genes (UreA, UreB, UreC, and UreG). This indicates that urea-acclimatized soil (Soil-MICP) possesses the potential to induce carbonate precipitation. Batch Pb2+ fixation experiments confirmed that the fixation efficiency of Soil-MICP on Pb2+ exceeded that of soil without MICP, attributed to the MICP process within the Soil-MICP group. Dynamic migration experiments revealed that the MICP reaction transformed exchangeable lead into carbonate-bound Pb, effectively impeding Pb2+ migration in the soil profile. Additionally, the migration rate of Pb2+ in Soil-MICP was influenced by varying urea amounts, pH levels, and pore flow rates, leading to a slowdown in migration. The Two-site sorption model aptly described the Pb2+ migration process in the Soil-MICP column. This study aims to elucidate the MICP biomineralization process, uncover the in-situ blocking mechanism of MICP on lead in soil, investigate the impact of Pb on key genes involved in urease metabolism, enhance the comprehension of the chemical morphology of lead mineralization products, and provide a theoretical foundation for MICP technology in preventing the migration of Pb2+ in soil profiles.


Assuntos
Carbonatos , Chumbo , Microbiologia do Solo , Poluentes do Solo , Solo , Solo/química , Urease/metabolismo , Precipitação Química
14.
Analyst ; 149(10): 2956-2965, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38597984

RESUMO

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.


Assuntos
Corantes Fluorescentes , Glioblastoma , Mitocôndrias , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Mitocôndrias/metabolismo , Viscosidade , Linhagem Celular Tumoral , Animais , Camundongos , Camundongos Nus , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Imagem Óptica
15.
Antiviral Res ; 225: 105877, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38561077

RESUMO

The conventional inactivated split seasonal influenza vaccine offers low efficacy, particularly in the elderly and against antigenic variants. Here, to improve the efficacy of seasonal vaccination for the elderly population, we tested whether supplementing seasonal bivalent (H1N1 + H3N2) split (S) vaccine with M2 ectodomain repeat and multi-subtype consensus neuraminidase (NA) proteins (N1 NA + N2 NA + flu B NA) on a virus-like particle (NA-M2e) would induce enhanced cross-protection against different influenza viruses in aged mice. Immunization with split vaccine plus NA-M2e (S + NA-M2e) increased vaccine-specific IgG antibodies towards T-helper type 1 responses and hemagglutination inhibition titers. Aged mice with NA-M2e supplemented vaccination were protected against homologous and heterologous viruses at higher efficacies, as evidenced by preventing weight loss, lowering lung viral loads, inducing broadly cross-protective humoral immunity, and IFN-γ+ CD4 and CD8 T cell responses than those with seasonal vaccine. Overall, this study supports a new strategy of NA-M2e supplemented vaccination to enhance protection against homologous and antigenically different viruses in the elderly.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Idoso , Humanos , Camundongos , Animais , Infecções por Orthomyxoviridae/prevenção & controle , Neuraminidase , Vírus da Influenza A Subtipo H3N2 , Estações do Ano , Anticorpos Antivirais , Proteção Cruzada , Camundongos Endogâmicos BALB C
16.
Vet Parasitol ; 328: 110169, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38520755

RESUMO

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.


Assuntos
Imunoglobulina E , Intestino Delgado , Doenças dos Ovinos , Animais , Imunoglobulina E/sangue , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologia , Intestino Delgado/imunologia , Intestino Delgado/parasitologia , Infecções por Cilióforos/veterinária , Infecções por Cilióforos/imunologia , Infecções por Cilióforos/parasitologia
17.
World J Gastroenterol ; 30(6): 523-526, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463027

RESUMO

Autoimmune pancreatitis (AIP) is a rare chronic autoimmune disorder. The diagnosis of AIP mainly depends on histopathology, imaging and response to treatment. Serum immunoglobulin 4 (IgG4) is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity. Serum IgG4 levels are normal in 15%-37% of type 1 AIP and most of type 2 AIP patients. In these patients, the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP. Therefore, discovery of new biomarkers is important for AIP diagnosis. Here, we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.


Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Humanos , Pancreatite Autoimune/diagnóstico , Diagnóstico Diferencial , Biomarcadores , Doença Crônica , Imunoglobulina G
18.
Heliyon ; 10(5): e26854, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463769

RESUMO

Background: Studies have been inconclusive on the risk for hemorrhage in patients with a history of aspirin use who underwent emergency external ventricular drainage (EVD)/intracranial pressure (ICP) probe placement. The aim of this study was to explore hemorrhage-related risk factors in order to reduce the risk for hemorrhage in these patients. Methods: Between July 2014 and July 2020, patients were retrospectively divided into EVD/ICP-related hemorrhage and non-hemorrhage groups. The collected data included age, gender, major diagnosis, medical history, imaging examinations, conventional coagulation test data, thromboelastography with platelet mapping (TEG-PM), surgical procedures and discharge conditions. Results: In total 94 patients, 21 in the hemorrhage group (15 males, 6 females) and 73 in the non-hemorrhage group (52 males, 21 females) were included. The majority of hemorrhages were recorded in EVD patients (19/21; 90.5%). Platelet AA pathway inhibition rate of ≥75% (sensitivity: 79.45% specificity: 52.38%) (P = 0.014) and SBP ≥125 mmHg (P = 0.006) were significantly related to hemorrhage. When the platelet AA pathway inhibition rate was ≥75% and the during-procedure SBP was ≥125 mmHg, the hemorrhage rate was significantly higher (83.3%) than with SBP <125 mmHg (6.7%) (P < 0.001). When the inhibition rate was <75%, there were no significant differences in the hemorrhage rates between the during-procedure SBP ≥125 mmHg group (17.2%) and the SBP <125 mmHg group (13.2%) (P > 0.05). Multivariate logistic regression analysis revealed that a platelet AA pathway inhibition rate ≥75% (OR = 5.183, 95% CI: 1.683-15.960) and during-procedure SBP ≥125 mmHg (OR = 4.609, 95% CI: 1.466-14.484) were independent risk factors for EVD/ICP-related hemorrhage. Conclusion: Patients with long-term aspirin therapy, a platelet AA pathway inhibition rate ≥75% and during-procedure SBP ≥125 mmHg had a significantly higher risk of hemorrhage, which could be reduced by adjusting the SBP to <125 mmHg.

19.
Arch Microbiol ; 206(4): 157, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480543

RESUMO

Potassium-solubilizing microorganisms are capable of secreting acidic chemicals that dissolve and release potassium from soil minerals, thus facilitating potassium uptake by plants. In this study, three potassium-dissolving filamentous fungi were isolated from the rhizosphere soil of a poplar plantation in Jiangsu Province, China. Phylogenetic analyses based on ITS, 18 S, and 28 S showed that these three isolates were most similar to Mortierella. These strains also possessed spherical or ellipsoidal spores, produced sporangia at the hyphal tip, and formed petal-like colonies on PDA media resembling those of Mortierella species. These findings, along with further phenotypic observations, suggest that these isolates were Mortierella species. In addition, the potassium-dissolution experiment showed that strain 2K4 had a relatively high potassium-solubilizing capacity among these isolated fungi. By investigating the influences of different nutrient conditions (carbon source, nitrogen source, and inorganic salt) and initial pH values on the potassium-dissolving ability, the optimal potassium-solubilization conditions of the isolate were determined. When potassium feldspar powder was used as an insoluble potassium source, isolate 2K4 exhibited a significantly better polysaccharide aggregation ability on the formed mycelium-potassium feldspar complex. The composition and content of organic acids secreted by strain 2K4 were further detected, and the potassium-dissolution mechanism of the Mortierella species and its growth promotion effect were discussed, using maize as an example.


Assuntos
Silicatos de Alumínio , Mortierella , Compostos de Potássio , Solo , Solo/química , Fosfatos , Mortierella/genética , Potássio , Rizosfera , Filogenia , Microbiologia do Solo , Fungos
20.
Ying Yong Sheng Tai Xue Bao ; 35(1): 111-123, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511447

RESUMO

Soil organic carbon (SOC) is the core component of terrestrial carbon (C) sink. Exploring the transformation and stabilization mechanism of SOC is key to understand the function of terrestrial C sink which copes with climate change. The traditional perspective is that plant residues are the initial source of SOC. The new concept of "soil microbial C pump" emphasizes that the synthesized products of soil microbial assimilation are important contributors to the stable SOC. This provides a new insight to the sequestration mechanism of SOC. Due to the complex and variable decomposition process of plant residues and the high heterogeneity of microbial residues, the transformation and stabilization mechanism of plant residues and microbial residues into SOC is still unclear. We reviewed research progress in plant and microbial residues, and introduced the characterization methods of quantification and transformation of plant residues and microbial residues, and also summarized the new findings on the transformation of plant and microbial residues into SOC. We further discussed the contribution and driving factors of microbial and plant-derived C to SOC. Finally, we prospected the future development direction and research focus in this field. This review would provide the scientific reference for the research of soil C sequestration in terrestrial ecosystem.


Assuntos
Ecossistema , Solo , Solo/química , Carbono , Sequestro de Carbono , Celulose , Plantas , Microbiologia do Solo
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