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1.
Clin Appl Thromb Hemost ; 30: 10760296241278345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39370845

RESUMO

Background: Platelet transfusion refractoriness (PTR) is a complication of multiple transfusions in patients with hematological malignancies. PTR may induce a series of adverse events, such as delaying the treatment of the primary disease and life-threatening bleeding. Early prediction of PTR holds promise in facilitating prompt adjustments to treatment strategies by clinicians. Methods: We collected the clinical data of 250 patients with acute myeloid leukemia (AML). Subsequently, the patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic-regression methods were used to select characteristic variables. Assessment of the model was conducted through the receiver operating characteristic (ROC), calibration curve and decision curve analysis (DCA). Results: Out of 250 patients with AML, 95 individuals (38.0%) experienced PTR. Among those with positive platelet associated antibodies (PAAs), the incidence of PTR was 66.7% (30/45), while among patients positive for human leukocyte antigen(HLA)-I antibodies, the PTR incidence was 56.5% (48/85). The final predictive model incorporated risk factors such as KIT mutations, splenomegaly, the number of HLA-I antibodies, and positive PAAs. A prediction nomogram model was constructed based on these four risk factors. The LASSO-logistic regression model demonstrated excellent discrimination, calibration, and clinical decision value. Conclusion: The LASSO-logistic regression model in the study can better predict the risk of PTR. The study includes both PAAs and HLA antibodies, expanding the field of work that has not been involved in the previous prediction model of PTR.


Assuntos
Leucemia Mieloide Aguda , Transfusão de Plaquetas , Humanos , Leucemia Mieloide Aguda/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso
2.
World J Surg Oncol ; 22(1): 263, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354502

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients. METHODS: Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit. RESULTS: Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set. CONCLUSIONS: The novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making.


Assuntos
Neoplasias da Vesícula Biliar , Nomogramas , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Prognóstico , Idoso , Curva ROC , Seguimentos , Estadiamento de Neoplasias , Estudos Retrospectivos , Colecistectomia/mortalidade , Colecistectomia/métodos
3.
Nucl Med Commun ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363633

RESUMO

OBJECTIVE: Pancreatic cancer is an increasing cause of cancer-related mortality, with persistently low survival rates. We investigated the clinical diagnostic value of the combination of preoperative serum carbohydrate antigen 19-9 (CA19-9), albumin-bilirubin (ALBI) score, and 18F-fluoro-2-deoxy-d-glucose PET integrated with computed tomography (18F-FDG PET/CT) imaging in pancreatic cancer preoperative resectability. METHODS: This study included 143 pancreatic cancer patients, including 68 preoperative resectable and 75 preoperative unresectable pancreatic cancer patients. Meanwhile, 67 patients with non-pancreatic cancer were included as the control group. The clinical data were collected. Serum CA19-9 level was measured by ELISA. The levels of total bilirubin and albumin were determined using a biochemical analyzer, with the ALBI score calculated. All patients underwent 18F-FDG PET/CT imaging. The consistency of the diagnosis was evaluated by the Kappa test. Logistic univariate and multivariate regression analyses were performed. The diagnostic efficacy of these parameters was evaluated using receiver operating characteristic (ROC) curves, and the optimal ROC curve thresholds were obtained using the Youden index. RESULTS: The preoperative serum CA19-9 and ALBI score of patients with preoperative resectable pancreatic cancer were increased, which helped diagnose preoperative resectable pancreatic cancer. 18F-FDG PET/CT imaging had diagnostic value for preoperative resectable pancreatic cancer. Preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging were independent influencing factors for pancreatic cancer preoperative resectability, and their combination had higher diagnostic value for preoperative resectable pancreatic cancer than any single of these indexes. CONCLUSION: The combination of preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging had high diagnostic value for pancreatic cancer preoperative resectability.

4.
Clin Exp Med ; 24(1): 210, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230837

RESUMO

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.


Assuntos
Plaquetas , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina/terapia , Testes de Função Plaquetária
5.
Sci Total Environ ; 952: 175939, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39218100

RESUMO

The use of plastic bowls (PB) has garnered increasing scrutiny due to the inevitable generation of microplastics (MPs) throughout their lifecycle. Despite this concern, there exists a limited understanding of the behaviors, toxicological effects, and mechanisms associated with aged PB (A-PB). This research investigated the photoaging properties of A-PB following ultraviolet irradiation and evaluated the neurotoxic impact of exposure to A-PB at environmentally relevant concentrations (0.001-1 mg/L) on Caenorhabditis elegans. Significant alterations in the crystallinity, elemental composition, and functional groups of A-PB were observed compared to virgin PB (V-PB), along with the emergence of environmentally persistent free radicals and reactive oxygen species. Toxicity assessments revealed that exposure to 0.1-1 mg/L A-PB induced greater neurotoxicity on locomotion behaviors compared to V-PB, as evidenced by marked reductions in head thrashes, body bends, wavelength, and mean amplitude. Exposure to A-PB also altered the fluorescence intensities and neurodegeneration percentage of dopaminergic, serotonergic, and GABAergic neurons, suggesting neuronal damage in the nematodes. Correspondingly, decreases in the levels of dopamine, serotonin, and GABA were noted together with significant drops in the expression of neurotransmitter-related genes (e.g., dat-1, tph-1, and unc-47). Correlation analyses established a significant positive relationship between these genes and locomotion behaviors. Further exploration showed the absence of locomotion behaviors in dat-1 (ok157), tph-1 (mg280), and unc-47 (e307) mutants, underscoring the pivotal roles of the dat-1, tph-1, and unc-47 genes in mediating neurotoxicity in C. elegans. This study sheds light on the photoaging characteristics and heightened toxicity of A-PB, elucidating the mechanisms driving A-PB-induced neurotoxicity.


Assuntos
Caenorhabditis elegans , Microplásticos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Microplásticos/toxicidade , Plásticos/toxicidade , Transmissão Sináptica/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Síndromes Neurotóxicas
6.
Genomics ; 116(5): 110940, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39303860

RESUMO

Seagrasses are ideal for studying plant adaptation to marine environments. In this study, the mitochondrial (mt) and chloroplast (cp) genomes of Ruppia sinensis were sequenced. The results showed an extensive gene loss in seagrasses, including a complete loss of cp-rpl19 genes in Zosteraceae, most cp-ndh genes in Hydrocharitaceae, and mt-rpl and mt-rps genes in all seagrasses, except for the mt-rpl16 gene in Phyllospadix iwatensis. Notably, most ribosomal protein genes were lost in the mt and cp genomes. The deleted cp genes were not transferred to the mt genomes through horizontal gene transfer. Additionally, a significant DNA transfer between seagrass organelles was found, with the mt genomes of Zostera containing numerous sequences from the cp genome. Rearrangement analyses revealed an unreported inversion of the cp genome in R. sinensis. Moreover, four positively selected genes (atp8, nad5, atp4, and ccmFn) and five variable regions (matR, atp4, atp8, rps7, and ccmFn) were identified.


Assuntos
Transferência Genética Horizontal , Genoma Mitocondrial , Cloroplastos/genética , Genoma de Cloroplastos , Alismatales/genética , Alismatales/metabolismo , Filogenia , Mitocôndrias/genética , Mitocôndrias/metabolismo
7.
Front Neural Circuits ; 18: 1435507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39268349

RESUMO

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.


Assuntos
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil) , Agonistas dos Canais de Cálcio , Canais de Cálcio Tipo L , Metilação de DNA , DNA Metiltransferase 3A , Depressão , Metionina , Animais , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Metionina/farmacologia , Masculino , Depressão/tratamento farmacológico , Depressão/metabolismo , Camundongos , Agonistas dos Canais de Cálcio/farmacologia , Metilação de DNA/efeitos dos fármacos , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Camundongos Endogâmicos C57BL , Antidepressivos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Lipopolissacarídeos/farmacologia , Modelos Animais de Doenças
8.
China CDC Wkly ; 6(30): 754-761, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39114317

RESUMO

Introduction: This study introduces a novel method for developing an advanced exposure conceptual model tailored for health risk assessment, focusing on microenvironments. Methods: The research was conducted at a major smelter in China to assess the health risks associated with trace metals (TMs) pollutants in the facility and the surrounding soil. Results: Deterministic risk assessment indicated that cobalt, cadmium, antimony, manganese, arsenic, plumbum, and mercury (Co, Cd, Sb, Mn, As, Pb, and Hg) necessitated further evaluation through probabilistic risk assessment to assess potential health risks to residents. The 95% quantile concentrations of other TMs were found to be within acceptable health risk limits. For the probabilistic risk assessment, exposure parameters such as body weight, respiration rate, and exposure duration were collected using a questionnaire. This targeted assessment of the residential microenvironment revealed it as the site of the highest carcinogenic (CR) and non-carcinogenic risks (NCR), with values ranging from 2.84×10-5 to 6.7×10-5 and 1.59 to 5.57, respectively. Conclusion: The primary contaminants posing the greatest health risks in residential and industrial areas have been identified as As, Pb, and Mn. The probabilistic health risk model, which focuses on microenvironmental factors, yields more precise results and offers a valuable tool for managing soil health risks.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 702-707, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926956

RESUMO

OBJECTIVE: To investigate the effect of progression of disease within 24 months (POD24) on overall survival (OS) in patients with mantle cell lymphoma (MCL), and compare the clinical characteristics between POD24 and non-POD24 patients. METHODS: A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020. According to the occurrence of POD24, the patients were grouped for prognostic evaluation and clinical characteristics comparison. RESULTS: Univariate Cox regression analysis showed that POD24, PLT, albumin, MIPI score, ECOG PS score, LDH were the factors influencing OS in newly diagnosed MCL patients (all P < 0.05). The results of multivariate Cox regression analysis showed that POD24ï¼»HR=16.797(95%CI : 3.671-76.861),P < 0.001ï¼½, albumin<40 g/Lï¼»HR=3.238(95%CI :1.095-9.572),P =0.034ï¼½ and ECOG PS score≥2ï¼»HR=4.005(95%CI :1.033-15.521),P =0.045ï¼½ were independent risk factors influencing OS in MCL patients. The incidence of PLT<100×109/L (33.3% vs 5.9%, P =0.033) and ECOG PS score ≥2 (45.5% vs 5.9%, P =0.040) were significantly higher in POD24 patients than those in non-POD24 patients. CONCLUSION: POD24 is an independent poor prognostic factor affecting the OS of MCL patients, and the patients with PLT<100×109/L and ECOG PS score≥2 at diagnosis have a higher probability of POD24.


Assuntos
Progressão da Doença , Linfoma de Célula do Manto , Humanos , Prognóstico , Estudos Retrospectivos , Masculino , Feminino , Taxa de Sobrevida , Modelos de Riscos Proporcionais , Pessoa de Meia-Idade
11.
Biochem Pharmacol ; 225: 116267, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723721

RESUMO

Acute liver failure (ALF) is a critical condition that can lead to substantial liver dysfunction. It is characterized by complex clinical manifestations and rapid progression, presenting significant challenges in diagnosis and treatment. We investigated the protective effect of mefunidone (MFD), a novel antifibrosis pyridone agent, on ALF in mice, and explored its potential mechanism of action. MFD pretreatment can alleviate lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced ALF, reduce hepatocyte apoptosis, and reduce inflammation and oxidative stress. Additionally, MFD alleviated LPS/D-GalN-stimulated reactive oxygen species (ROS) production and cell death in AML12 cells. RNA sequencing enrichment analysis showed that MFD significantly affected the Mitogen-Activated Protein Kinase (MAPK) pathway. In vivo and in vitro experiments showed that MFD inhibited MKK4 and JNK phosphorylation. JNK activation caused by MKK4 and JNK activators could eliminate the therapeutic effect of MFD on AML12. In addition, MFD pretreatment alleviated ConA-induced ALF, reduced inflammation and oxidative stress in mice, and reduced mouse mortality. These results suggest that MFD can potentially protect against ALF, partially by inhibiting the MKK4-JNK pathway, and is a promising new therapeutic drug for ALF.


Assuntos
Falência Hepática Aguda , MAP Quinase Quinase 4 , Piperazinas , Piridonas , Animais , Masculino , Camundongos , Linhagem Celular , Galactosamina/toxicidade , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase 4/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Piridonas/farmacologia , Piridonas/uso terapêutico , Piperazinas/farmacologia , Piperazinas/uso terapêutico
12.
Virus Res ; 346: 199394, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38735439

RESUMO

Hantaan virus (HTNV) is a major public health concern due to its ability to cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Symptoms of HFRS include fever, hemorrhage, immune dysfunction and renal impairment, and severe cases can be fatal. T cell-mediated adaptive immune responses play a pivotal role in countering HTNV infection. However, our understanding of HTNV and T cell interactions in the disease progression is limited. In this study, we found that human CD4+ T cells can be directly infected with HTNV, thereby facilitating viral replication and production. Additionally, T-cell immunoglobulin and mucin 1 (TIM-1) participated in the process of HTNV infection of Jurkat T cells, and further observed that HTNV enters Jurkat T cells via the clathrin-dependent endocytosis pathway. These findings not only affirm the susceptibility of human CD4+ T lymphocytes to HTNV but also shed light on the viral tropism. Our research elucidates a mode of the interaction between the virus infection process and the immune system. Critically, this study provides new insights into the pathogenesis of HTNV and the implications for antiviral research.


Assuntos
Linfócitos T CD4-Positivos , Vírus Hantaan , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Vírus Hantaan/imunologia , Vírus Hantaan/fisiologia , Células Jurkat , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Replicação Viral , Endocitose , Febre Hemorrágica com Síndrome Renal/virologia , Febre Hemorrágica com Síndrome Renal/imunologia , Interações Hospedeiro-Patógeno/imunologia , Tropismo Viral
13.
J Agric Food Chem ; 72(19): 10781-10793, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709780

RESUMO

In this study, 20-day-old soybean plants were watered with 100 mL of 100 mM NaCl solution and sprayed with silica nanoparticles (SiO2 NPs) or potassium silicate every 3 days over 15 days, with a final dosage of 12 mg of SiO2 per plant. We assessed the alterations in the plant's growth and physiological traits, and the responses of bacterial microbiome within the leaf endosphere, rhizosphere, and root endosphere. The result showed that the type of silicon did not significantly impact most of the plant parameters. However, the bacterial communities within the leaf and root endospheres had a stronger response to SiO2 NPs treatment, showing enrichment of 24 and 13 microbial taxa, respectively, compared with the silicate treatment, which led to the enrichment of 9 and 8 taxonomic taxa, respectively. The rhizosphere bacterial communities were less sensitive to SiO2 NPs, enriching only 2 microbial clades, compared to the 8 clades enriched by silicate treatment. Furthermore, SiO2 NPs treatment enriched beneficial genera, such as Pseudomonas, Bacillus, and Variovorax in the leaf and root endosphere, likely enhancing plant growth and salinity stress resistance. These findings highlight the potential of SiO2 NPs for foliar application in sustainable farming by enhancing plant-microbe interactions to improve salinity tolerance.


Assuntos
Bactérias , Glycine max , Nanopartículas , Rizosfera , Silício , Glycine max/microbiologia , Glycine max/crescimento & desenvolvimento , Glycine max/efeitos dos fármacos , Glycine max/química , Nanopartículas/química , Bactérias/classificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Silício/farmacologia , Silício/química , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Microbiologia do Solo , Microbiota/efeitos dos fármacos , Folhas de Planta/química , Folhas de Planta/microbiologia , Folhas de Planta/crescimento & desenvolvimento , Endófitos/fisiologia , Endófitos/efeitos dos fármacos , Dióxido de Silício/química , Estresse Salino
14.
Chem Biodivers ; 21(3): e202400017, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321767

RESUMO

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.


Assuntos
Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacologia , Alcaloides/química
15.
Cell Biol Toxicol ; 40(1): 12, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340268

RESUMO

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.


Assuntos
Asma , Dibenzotiepinas , Pneumonia , Piridonas , Triazinas , Animais , Camundongos , Asma/tratamento farmacológico , Asma/metabolismo , Morfolinas/farmacologia , Morfolinas/uso terapêutico
16.
Environ Res ; 250: 118544, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38408630

RESUMO

Wastewater-based epidemiology (WBE) is amply used for estimating human consumption of chemicals, yet information on regional variation of pharmaceuticals and their environmental fate are scarce. Thus, this study aims to estimate the consumption of three cardiovascular, four non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), and four psychoactive pharmaceuticals between urban and suburban catchments in China by WBE, and to explore their removal efficiencies and ecological risks. Eleven analytes were detected in both influent and effluent samples. The estimated consumptions ranged from

Assuntos
Águas Residuárias , Poluentes Químicos da Água , China , Poluentes Químicos da Água/análise , Águas Residuárias/análise , Águas Residuárias/química , Preparações Farmacêuticas/análise , Cidades , Humanos , Medição de Risco , Anti-Inflamatórios não Esteroides/análise , Monitoramento Ambiental , Vigilância Epidemiológica Baseada em Águas Residuárias , Psicotrópicos/análise
17.
Hematology ; 29(1): 2304483, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38251872

RESUMO

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.


Assuntos
Linfoma de Células T Periférico , Humanos , Prognóstico , Linfoma de Células T Periférico/tratamento farmacológico , Estudos Retrospectivos , Progressão da Doença
18.
J Orthop Res ; 42(5): 993-1000, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38047481

RESUMO

Developmental dysplasia of the hip (DDH) is a developmental disorder characterized by acetabular dysplasia leading to early osteoarthritis. This study examines the role of endoplasmic reticulum stress (ERS) in chondrocyte apoptosis and cartilage degeneration within a DDH model. In the rat model of DDH, created using a swaddling technique, significant deformities in the femoral head and acetabulum were observed, alongside an upregulation of matrix metalloproteinase-13 in acetabular cartilage. We also noted increased levels of apoptosis and ERS-related factors in the acetabular cartilage of DDH models. Additionally, rat chondrocytes exposed to high-magnitude cyclic tensile strain (CTS, 1 Hz, 10% equibiaxial strain) in vitro exhibited elevated ERS and increased apoptosis. Importantly, treatment with the ERS inhibitor 4-phenylbutyric acid effectively suppressed apoptosis induced by CTS in chondrocytes. Our findings suggest that ERS contributes to the upregulation of apoptosis-related factors in chondrocytes within the DDH model, indicating the potential of ERS modulation as a therapeutic approach for DDH-related cartilage degeneration.


Assuntos
Doenças das Cartilagens , Condrócitos , Ratos , Animais , Cartilagem , Apoptose , Estresse do Retículo Endoplasmático
20.
PLoS One ; 18(9): e0291738, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733688

RESUMO

Regular use of Thai kratom has been linked to reduced blood triglyceride levels and body mass index (BMI) in healthy individuals. We analyzed Green Thai Kratom (GTK) and Red Thai Kratom (RTK) to investigate their effects on pancreatic digestive enzymes. The ethanol extracts of GTK and RTK inhibited lipase activity more strongly than alpha-glucosidase activity, suggesting the presence of lipase inhibitors. Mitragynine, the major compound in GTK, showed potent lipase inhibition and moderate alpha-glucosidase inhibition. Quercetin, found in both extracts, strongly inhibited alpha-glucosidase but had limited effects on lipase. These findings suggest that mitragynine and quercetin may hinder triglyceride and starch digestion. Combination inhibition studies revealed synergistic effects between mitragynine and quercetin on alpha-glucosidase activity. Additionally, both GTK and RTK extracts reduced fat accumulation in 3T3-L1 adipocyte cells, with quercetin specifically inhibiting Acetyl-CoA carboxylase 1 (ACC1), a key enzyme in fatty acid biosynthesis. Thus, GTK and RTK extracts, particularly mitragynine and quercetin, exhibit potential anti-obesity effects. We report the novel finding that Thai kratom inhibits de novo fatty acid synthesis by targeting ACC1, resulting in decreased fat accumulation in adipocytes. Regular use of Thai kratom in specific populations may improve blood triglyceride levels and reduce BMI by inhibiting lipase, alpha-glucosidase, and ACC1 activity. Further clinical trials are needed to determine optimal dosage, duration, toxicity levels, and potential side effects of Kratom use.


Assuntos
Carboxiliases , Mitragyna , Humanos , alfa-Glucosidases , Ácidos Graxos , Lipase , Quercetina/farmacologia
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