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1.
Ann Hematol ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761184

RESUMO

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

2.
Ann Hematol ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805037

RESUMO

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

3.
J Integr Neurosci ; 23(5): 103, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38812389

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.


Assuntos
Hipóxia-Isquemia Encefálica , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Recém-Nascido , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Antioxidantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
4.
J Environ Manage ; 351: 119886, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142601

RESUMO

Comparing with single phytohormone application, applying multiple phytohormones to microalgae-based wastewater treatment systems can offer more extensive growth-promoting and stress-protecting effects for microalgae, yet the advantage of stress-relieving salicylic acid (SA) under combined phytohormones application scenario has not been exploited. Employing the improved capillary-driven attached microalgae culturing device (CD-PBR) previously used for single phytohormone application, this study compared the effects of mixed and single phytohormone(s) addition under as low as 10-7 M dosage. In order to make the best of SA for its stress-relieving property, postponed SA addition combined with applying other phytohormone(s) at the beginning of microalgae cultivation was also investigated. Combination of 10-6 M 6-benzylaminopurine (6-BA) with 10-7 M SA was sufficient for enhancing growth-promoting effects and anti-oxidative responses for attached Chlorella sp., while indole-3-acetic acid (IAA) addition was unnecessary. Combination of 6-BA addition at the beginning while postponed SA addition on Day 4 could further sustain such beneficial effects, while removing up to 99.7% total nitrogen (TN) and 97.9% total phosphorus (TP) from the bulk liquid. These results provided innovative strategies on mixed phytohormones addition for microalgae.


Assuntos
Chlorella , Microalgas , Reguladores de Crescimento de Plantas/farmacologia , Biofilmes , Nitrogênio , Biomassa
5.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2585-2596, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812159

RESUMO

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ciclo-Oxigenase 2 , Fígado , NF-kappa B , Panax , Saponinas , Transdução de Sinais , Animais , Acetaminofen/efeitos adversos , Acetaminofen/toxicidade , Camundongos , Panax/química , Masculino , Saponinas/farmacologia , Saponinas/administração & dosagem , NF-kappa B/genética , NF-kappa B/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia
6.
Clin Exp Immunol ; 214(3): 260-274, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-37586814

RESUMO

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , Animais , Humanos , Camundongos , Asma/metabolismo , Interleucinas/metabolismo , Pulmão/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Pyroglyphidae , Camundongos Endogâmicos BALB C
7.
J Appl Microbiol ; 134(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36597783

RESUMO

Acinetobacter baumannii is a strictly aerobic, nonmotile, nonfermenting, gram-negative bacillus. It is a highly infectious and invasive pathogen with high mortality and morbidity rates among immunodeficient patients. Due to increasing levels of drug resistance and the inefficiency of existing antimicrobial treatments, it is crucial to develop novel agents to control this pathogen. Several recent studies have investigated virulence factors that are associated with the pathogenesis of A. baumannii, and could thus serve as novel therapeutic targets. The present review comprehensively summarizes the current understanding of these virulence factors and their mechanisms in A. baumannii. We also highlight factors that could be potential therapeutic targets, as well as list candidate virulence factors for future researchers and clinical practitioners.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Anti-Infecciosos , Humanos , Fatores de Virulência/genética , Virulência , Infecções por Acinetobacter/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla
8.
J Appl Microbiol ; 134(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37037774

RESUMO

AIMS: To investigate the capability, properties, and molecular mechanism of inulin fermentation by lactic acid bacteria (LAB) from Sichuan pickle. METHODS AND RESULTS: A total of 79 LAB strains were purified from 30 aged Sichuan pickle brine samples, and only 21 Lactiplantibacillus plantarum strains (26.58%, 21/79) derived from 15 samples grew well through utilizing inulin as a carbon source. The fermentation tests through using long-chain inulin (lc-inulin) as a carbon source showed that only 6 L. plantarum strains grew well, while other 15 strains could only utilize short-chain oligofructose (FOS), and thin-layer chromatography analysis evidenced a strain specificity of inulin consumption patterns. Lactiplantibacillus plantarum YT041 is a vigorous inulin fermenter, and whole genome sequencing data revealed that sacPTS1 and fosRABCDXE operons might be associated with the fermentation of FOS and lc-inulin, respectively. CONCLUSIONS: The phenotype of inulin consumption is commonly present in LAB from Sichuan pickle, which is strain-specific and largely depends on their specific ecological niche and degree of polymerization.


Assuntos
Alimentos Fermentados , Lactobacillales , Lactobacillus plantarum , Inulina/metabolismo , Lactobacillales/metabolismo , Genômica , Fenótipo , Alimentos Fermentados/microbiologia , Fermentação , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo
9.
BMC Med Imaging ; 23(1): 131, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37715139

RESUMO

OBJECTIVE: To identify CT features and establish a nomogram, compared with a machine learning-based model for distinguishing gastrointestinal heterotopic pancreas (HP) from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: This retrospective study included 148 patients with pathologically confirmed HP (n = 48) and GIST (n = 100) in the stomach or small intestine that were less than 3 cm in size. Clinical information and CT characteristics were collected. A nomogram on account of lasso regression and multivariate logistic regression, and a RandomForest (RF) model based on significant variables in univariate analyses were established. Receiver operating characteristic (ROC) curve, mean area under the curve (AUC), calibration curve and decision curve analysis (DCA) were carried out to evaluate and compare the diagnostic ability of models. RESULTS: The nomogram identified five CT features as independent predictors of HP diagnosis: age, location, LD/SD ratio, duct-like structure, and HU lesion/pancreas A. Five features were included in RF model and ranked according to their relevance to the differential diagnosis: LD/SD ratio, HU lesion/pancreas A, location, peritumoral hypodensity line and age. The nomogram and RF model yielded AUC of 0.951 (95% CI: 0.842-0.993) and 0.894 (95% CI: 0.766-0.966), respectively. The DeLong test found no statistically significant difference in diagnostic performance (p > 0.05), but DCA revealed that the nomogram surpassed the RF model in clinical usefulness. CONCLUSION: Two diagnostic prediction models based on a nomogram as well as RF method were reliable and easy-to-use for distinguishing between HP and GIST, which might also assist treatment planning.


Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Nomogramas , Estudos Retrospectivos , Pâncreas/diagnóstico por imagem , Aprendizado de Máquina , Tomografia Computadorizada por Raios X
10.
J Digit Imaging ; 36(6): 2554-2566, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37578576

RESUMO

This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Fenótipo , Estudos Retrospectivos , Método Duplo-Cego
11.
Molecules ; 28(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36771172

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with an extremely poor prognosis and low survival rate. Due to its inconspicuous symptoms, PDAC is difficult to diagnose early. Most patients are diagnosed in the middle and late stages, losing the opportunity for surgery. Chemotherapy is the main treatment in clinical practice and improves the survival of patients to some extent. However, the improved prognosis is associated with higher side effects, and the overall prognosis is far from satisfactory. In addition to resistance to chemotherapy, PDAC is significantly resistant to targeted therapy and immunotherapy. The failure of multiple treatment modalities indicates great dilemmas in treating PDAC, including high molecular heterogeneity, high drug resistance, an immunosuppressive microenvironment, and a dense matrix. Nanomedicine shows great potential to overcome the therapeutic barriers of PDAC. Through the careful design and rational modification of nanomaterials, multifunctional intelligent nanosystems can be obtained. These nanosystems can adapt to the environment's needs and compensate for conventional treatments' shortcomings. This review is focused on recent advances in the use of well-designed nanosystems in different therapeutic modalities to overcome the PDAC treatment dilemma, including a variety of novel therapeutic modalities. Finally, these nanosystems' bottlenecks in treating PDAC and the prospect of future clinical translation are briefly discussed.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Microambiente Tumoral , Neoplasias Pancreáticas
12.
Sheng Li Xue Bao ; 75(1): 49-58, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36859834

RESUMO

Interleukin 6 (IL-6), an important component of cardiac microenvironment, favors cardiac repair by improving cardiomyocyte regeneration in different models. This study aimed to investigate the effects of IL-6 on stemness maintenances and cardiac differentiation of mouse embryonic stem cells (mESCs). The mESCs were treated with IL-6 for two days, and then subjected to CCK-8 essay for proliferation analysis and quantitative real-time PCR (qPCR) to evaluate the mRNA expression of genes related to stemness and germinal layers differentiation. Phosphorylation levels of stem cell-related signal pathways were detected by Western blot. siRNA was used to interfere the function of STAT3 phosphorylation. Cardiac differentiation was investigated by the percentage of beating embryoid bodies (EBs) and qPCR analysis of cardiac progenitor markers and cardiac ion channels. IL-6 neutralization antibody was applied to block the endogenous IL-6 effects since the onset of cardiac differentiation (embryonic day of 0, EB0). The EBs were collected on EB7, EB10 and EB15 to investigate the cardiac differentiation by qPCR. On EB15, Western blot was applied to investigate the phosphorylation of several signaling pathways, and immunochemistry staining was adopted to trace the cardiomyocytes. IL-6 antibody was administered for two days (short term) on EB4, EB7, EB10 or EB15, and percentages of beating EBs at late developmental stage were recorded. The results showed that exogenous IL-6 promoted mESCs proliferation and favored maintenances of pluripotency, evidenced by up-regulated mRNA expression of oncogenes (c-fos, c-jun) and stemness markers (oct4, nanog), down-regulated mRNA expression of germ layer genes (branchyury, FLK-1, pecam, ncam, sox17), and increased phosphorylation of ERK1/2 and STAT3. siRNA targeting JAK/STAT3 partially attenuated the effects of IL-6 on cell proliferation and mRNA expression of c-fos and c-jun. During differentiation, long term IL-6 neutralization antibody application decreased the percentage of beating EBs, down-regulated mRNA expression of ISL1, GATA4, α-MHC, cTnT, kir2.1, cav1.2, and declined the fluorescence intensity of cardiac α actinin in EBs and single cell. Long term IL-6 antibody treatment decreased the phosphorylation of STAT3. In addition, short term (2 d) IL-6 antibody treatment starting from EB4 significantly reduced the percentage of beating EBs in late development stage, while short term IL-6 antibody treatment starting from EB10 significantly increased the percentage of beating EBs on EB16. These results suggest that exogenous IL-6 promotes mESCs proliferation and favors stemness maintenance. Endogenous IL-6 regulates mESC cardiac differentiation in a development-dependent manner. These findings provide important basis for the study of microenvironment on cell replacement therapy, as well as a new perspective for understanding the pathophysiology of heart diseases.


Assuntos
Interleucina-6 , Células-Tronco Embrionárias Murinas , Animais , Camundongos , Diferenciação Celular , Proteínas Proto-Oncogênicas c-fos , RNA Mensageiro
13.
Biochem Biophys Res Commun ; 624: 40-46, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-35932578

RESUMO

Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus (DM) and has become the second cause of end-stage renal disease (ESRD). This study intends to investigate the molecular mechanism of increased mitochondrial fission in podocytes under the effect of high glucose (HG), and to preliminarily study the role of mitochondrial fission factor (MFF)-mediated mitochondrial fission in podocyte injury of DN. In vitro studies, we found that HG induced increased mitochondrial fission and podocyte damage. At the same time MFF mRNA and protein levels was increased, suggesting that MFF was transcriptional upregulated under HG conditions. Consistent with this, in vivo studies found that mitochondrial fission was also significantly increased in podocytes of diabetic nephropathy mice, and MFF expression was up-regulated. Therefore, our study proves that mitochondrial fission increases in podocytes under DM both in vitro and in vivo, and the up-regulation of MFF expression may be one of the reasons for the increase of mitochondrial fission. After inhibiting the expression of MFF, the survival rate of podocytes was significantly decreased under HG conditions, suggesting that MFF may play a protective role in podocyte injury in DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Animais , Apoptose , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Camundongos , Dinâmica Mitocondrial , Podócitos/metabolismo , Regulação para Cima
14.
Bioorg Chem ; 120: 105639, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35093691

RESUMO

Dengue virus, belonging to a genus Flavivirus, caused public health problem in recent years. One controversial vaccine of DENV was approved and there is no antiviral for the clinic treatment of DENV, therefore, efficient antivirals to DENV are of great medical significance. In this study, we conducted the design, synthesis, cell-based and target-based activity evaluation of 28 compounds based on indoline structural skeleton against DENV infection. Among them, 13 active compounds against DENV infection were discovered and their structure-activity relationship (SAR) was summarized. In this study, indoline carbohydrazine has derived more active compounds than indoline carboamide. It is discovered that TBS group exhibits a good pharmacophore to enhance anti-DENV activity. Further exploration indicated that post-treatment acts as effective time of addition and compound 15 targeting the post-entry stages of DENV2 viral life cycle. SPR imaging results support there are strong interaction of 13 and 15 with RdRp and compounds 13 and 15 reduce RdRp enzymatic activity, revealing that RdRp of DENV NS5 is the drug target for these series of compounds. Molecular docking deciphered the relationship of the structural feature with the putative binding mode by 13 and 15 with RdRp domain of DENV2 NS5 by hydrogen bonds and hydrophobic interactions to establish the fitted low energy conformation. Future studies will focus on designing more potent inhibitors for the treatment and prevention of dengue virus replication and infection, and understanding the more profound underlying structural features of inhibitors and drug action of the mechanism.


Assuntos
Vírus da Dengue , Antivirais/química , Indóis , Simulação de Acoplamento Molecular , RNA Polimerase Dependente de RNA , Relação Estrutura-Atividade
15.
Age Ageing ; 51(1)2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34673897

RESUMO

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.


Assuntos
Fragilidade , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Mieloma Múltiplo/diagnóstico , Estudos Prospectivos
16.
Inorg Chem ; 60(10): 7364-7371, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33891407

RESUMO

Photocatalytic carbon dioxide reduction (CO2RR) is considered to be a promising sustainable and clean approach to solve environmental issues. Polyoxometalates (POMs), with advantages in fast, reversible, and stepwise multiple-electron transfer without changing their structures, have been promising catalysts in various redox reactions. However, their performance is often restricted by poor thermal or chemical stability. In this work, two transition-metal-modified vanadoborate clusters, [Co(en)2]6[V12B18O54(OH)6]·17H2O (V12B18-Co) and [Ni(en)2]6[V12B18O54(OH)6]·17H2O (V12B18-Ni), are reported for photocatalytic CO2 reduction. V12B18-Co and V12B18-Ni can preserve their structures to 200 and 250 °C, respectively, and remain stable in polar organic solvents and a wide range of pH solutions. Under visible-light irradiation, CO2 can be converted into syngas and HCOO- with V12B18-Co or V12B18-Ni as catalysts. The total amount of gaseous products and liquid products for V12B18-Co is up to 9.5 and 0.168 mmol g-1 h-1. Comparing with V12B18-Co, the yield of CO for V12B18-Ni declines by 1.8-fold, while that of HCOO- increases by 35%. The AQY of V12B18-Co and V12B18-Ni is 1.1% and 0.93%, respectively. These values are higher than most of the reported POM materials under similar conditions. The density functional theory (DFT) calculations illuminate the active site of CO2RR and the reduction mechanism. This work provides new insights into the design of stable, high-performance, and low-cost photocatalysts for CO2 reduction.

17.
Acta Odontol Scand ; 79(7): 536-544, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33843405

RESUMO

OBJECTIVE: To establish and verify models predictive of thin periodontal phenotype and alveolar fenestration/dehiscence in the anterior teeth of patients with skeletal Class III malocclusion. MATERIAL AND METHODS: Retrospective data of 669 anterior teeth (305 in maxillae and 364 in mandibles) from 80 patients with skeletal Class III malocclusion before augmented corticotomy were collected. Distribution of thin periodontal phenotype and alveolar fenestration and dehiscence were evaluated and their associations with potential influencing factors were explored using univariate and multivariate analyses. The predictive models were visualized as nomograms, the accuracy of which was tested by receiver operating curve analyses. RESULTS: Thin phenotype was associated with Mazza bleeding index, sex, tooth type, probing depth and width of keratinized gingiva (WKG). Labial dehiscence was associated with age, jaw, labial bone thickness, mandibular plane angle, sagittal root position (SRP), sex, tooth type, and WKG. Labial fenestration was associated with sex, tooth type, SRP, and periodontal phenotype. The areas under the curves of nomogram prediction models for periodontal phenotype, alveolar dehiscence, and alveolar fenestration were 0.84, 0.81, and 0.73, respectively. CONCLUSIONS: Female sex, lateral incisor, and limited WKG may be risk factors for thin periodontal phenotype. Age, canine, male sex, mandible, thin labial bone thickness, and root positioned against the labial plate may be risk factors for labial dehiscence; and female sex, thick phenotype, root positioned against the labial plate, lateral incisor, and canine may be risk factors for labial fenestration. The predictive performance of the models was acceptable.


Assuntos
Má Oclusão Classe III de Angle , Nomogramas , China , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Incisivo , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Estudos Retrospectivos
18.
J Cancer Educ ; 36(3): 452-462, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33057985

RESUMO

The emerging discipline of oncofertility advocates for the timely provision of fertility preservation (FP) to all cancer patients of childbearing age by healthcare providers. A lack of practice due to limited FP-related knowledge was found among healthcare providers. A systematic review was undertaken on the educational programs on FP for healthcare providers. An initial search was performed in MEDLINE, PsycINFO, CINAHL, Web of Science, PubMed, and Scopus databases in October 2019. This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Among the 160 articles that were identified, five relevant articles published between 2009 and 2019 were reviewed. Of the five studies, three were quantitative nonrandomized studies, one was a randomized controlled trial, and one was a qualitative study. Three programs were relevant to oncology nurses, one was relevant to social workers as well as nurses, and one was relevant to oncology fellows and residents. The four programs significantly increased healthcare providers' knowledge about FP, but clinical practice was only improved in the Educating Nurses about Reproductive Issues in Cancer Healthcare program (P < 0.01). Nevertheless, most of the studies used a self-made questionnaire or tool to assess the effects of the training programs. The educational programs improved the FP-related knowledge of healthcare providers but lacked the high-quality randomized controlled trials needed to provide robust evidence on the effectiveness of training programs using standard tools. More training projects should be developed based on learning theories or models to improve oncofertility care in clinical practice.


Assuntos
Preservação da Fertilidade , Neoplasias , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Am J Orthod Dentofacial Orthop ; 159(3): 312-320, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33526298

RESUMO

INTRODUCTION: This study investigated the prevalence of and risk factors for alveolar fenestration and dehiscence in the anterior teeth of Chinese patients with skeletal Class III malocclusion. METHODS: This study included clinical and radiographic examinations and intraoperative observations of 460 anterior teeth from 54 patients who underwent corticotomy and periodontal regenerative surgery before orthodontic treatment. Fenestration and dehiscence were detected and recorded during open-flap surgery. Univariate and multivariate analyses were performed to assess relationships between fenestration and dehiscence and age, sex, history of previous orthodontic treatment, mandibular plane angle, dentition, tooth position, sagittal root position, periodontal biotype, gingival recession, width of keratinized gingiva, and width of the basal bone. RESULTS: The prevalence of buccal alveolar bone defects was 16.1% (fenestration) and 20.7% (dehiscence) at the tooth level. Multivariate logistic regressions showed that fenestration was significantly associated with tooth position (canine vs central incisor, odds ratio [OR] = 3.324; P = 0.006; lateral incisor vs central incisor, OR = 5.588; P  <0.001), and sagittal root position (buccally positioned vs centrally positioned, OR = 5.865; P = 0.025). Dehiscence was significantly associated with dentition (mandible vs maxilla, OR = 11.685; P  <0.001), tooth position (canine vs central incisor, OR = 3.863; P = 0.007), age (OR = 1.227; P = 0.010), sex (male vs female, OR = 5.530; P = 0.026), and history of orthodontic treatment (yes vs no, OR = 4.773; P = 0.028). CONCLUSIONS: Buccally positioned teeth in the osseous housing, lateral incisors, and canines were more likely to exhibit alveolar fenestration. Mandibular teeth and canines, patients who were older, were male, and had a history of orthodontic treatment, were more likely to exhibit alveolar dehiscence.


Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , China/epidemiologia , Feminino , Humanos , Masculino , Mandíbula , Prevalência , Fatores de Risco
20.
J Prosthodont ; 30(8): 645-650, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33938077

RESUMO

The failing dentition of partially edentulous individuals may be used as an initial reference for stackable restrictive surgical guides during full-arch immediate implant placement. The stackable guide option derived from a digital workflow increases the predictability of the performance of bone reduction, immediate implant placement, and immediate loading of provisional implant-supported fixed dental prostheses. The present paper aims to report a practical approach to design and produce a metal framework with occlusal rests to facilitate the use of a tooth-supported surgical guide when full-arch immediate implant placement is indicated in patients with failing dentition.


Assuntos
Implantes Dentários , Carga Imediata em Implante Dentário , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Humanos , Tecnologia , Fluxo de Trabalho
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