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1.
ACS Omega ; 9(25): 27192-27203, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947808

RESUMO

Camellia polyodonta flowers contain limited information available regarding the composition of their bioactive compounds and activity. The objective of this study was to identify phenolic compounds and investigate the effect of different solvents (ethanol and methanol) on the phenolic content and antioxidant activity in C. polyodonta flowers. The analysis using UPLC-Q-TOF-MS/MS revealed the presence of 105 phytochemicals and the most common compounds were flavonols, procyanidins, and ellagitannins. Interestingly, flavonol triglycosides were identified for the first time in these flowers. The study demonstrated that the concentration of the solvent had a significant impact on the total phenolic compound (TPC), total flavonoid compound (TFC), and total proanthocyanidin content (TPAC). The TPC, TFC, and TPAC showed a remarkable increase with the increasing concentration of the solvent, reaching their maximum levels (138.23 mg GAE/g DW, 421.62 mg RE/g DW, 60.77 mg PB2E/g DW) at 70% ethanol. However, the total anthocyanin content reached its maximum at low concentrations (0.49 mg CGE/g DW). Similar trends were observed in the antioxidant activity, as measured by the DPPH· assay (DPPH radical scavenging activity), ABTS·+ assay (ABTS radical cation scavenging activity), and FRAP assay (Ferric reducing antioxidant power). The maximum antioxidant activity was observed at 100% solvents and 70% methanol. Among the 14 individual phenolic compounds, 70% methanol yielded the highest content for 8 (cyanidin-3-O-glucoside, procyanidin B2, procyanidin B4, epicatechin, rutin, kaempferol-3-O-rutinoside, astragaline and quercitrin) out of the 14 compounds. Additionally, it was found that epicatechin was the most abundant phenolic compound, accounting for approximately 20339.37 µg/g DW. Based on these findings, it can be concluded that 70% methanol is the most effective solvent for extracting polyphenols from C. polyodonta flowers. These results provided chemical information and potential antioxidant value for further research in C. polyodonta flowers.

2.
Pharm Res ; 41(6): 1271-1284, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38839720

RESUMO

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.


Assuntos
Liberação Controlada de Fármacos , Microesferas , Polietilenoglicóis , Ratos Sprague-Dawley , Polietilenoglicóis/química , Animais , Progesterona/química , Progesterona/administração & dosagem , Progesterona/farmacocinética , Preparações de Ação Retardada/química , Ratos , Cristalização , Portadores de Fármacos/química , Tamanho da Partícula , Poliésteres/química , Feminino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Disponibilidade Biológica
3.
Eur J Pharmacol ; 977: 176703, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38839028

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.


Assuntos
Nefrite Lúpica , Camundongos Endogâmicos BALB C , Proteína Fosfatase 2 , Estruturas Linfoides Terciárias , Animais , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/metabolismo , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Camundongos , Estruturas Linfoides Terciárias/patologia , Feminino , Camundongos Endogâmicos MRL lpr , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Modelos Animais de Doenças , Baço/efeitos dos fármacos , Baço/patologia , Baço/imunologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Piperazinas
4.
Nat Commun ; 15(1): 3884, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719909

RESUMO

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.


Assuntos
Antígeno B7-1 , Antígeno B7-H1 , Vesículas Extracelulares , Receptor de Morte Celular Programada 1 , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Humanos , Antígeno B7-1/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Camundongos , Linhagem Celular Tumoral , Feminino , Neoplasias/imunologia , Neoplasias/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Masculino , Microambiente Tumoral/imunologia
5.
Hormones (Athens) ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819742

RESUMO

PURPOSE: Cardiovascular disease is one of the leading causes of mortality in patients with obesity. Metabolically healthy obesity (MHO), in which people do not have metabolic disorders, is a transient state of obesity. However, over the long term, a proportion of individuals with MHO develop metabolic syndrome (MetS). We aimed to investigate the effect of substantial weight loss following bariatric surgery in MHO on carotid intima-media thickness (CIMT) and pulse-wave velocity (PWV), which are independent predictors of subclinical atherosclerosis. METHODS: This prospective study included 38 patients (34 women, four men) undergoing bariatric surgery who had severe obesity but without comorbidities (hypertension, diabetes, and hyperlipidemia), and 28 control individuals who were matched for age and sex. CIMT and PWV of the left common carotid artery were measured. At 12-month follow-up after bariatric surgery, measurements were repeated in the 38 patients with obesity. RESULTS: Mean baseline body mass index (BMI) in the MHO group was 40.55 ± 3.59 kg/m2, which decreased by 33.1% after bariatric surgery. Compared with controls, CIMT and PWV were increased in MHO (543.53 ± 55.29 vs. 407.82 ± 53.09 µm, 6.70 ± 1.22 vs. 5.45 ± 0.74 m/s, respectively; all P < 0.001). At 12 months post-bariatric surgery, CIMT in MHO was lower than baseline (466.79 ± 53.74 vs. 543.53 ± 55.29 µm, P = 0.009), but PWV was not significantly different from baseline (6.27 ± 0.86 vs. 6.70 ± 1.22 m/s, P = 0.132). Multivariate regression showed that BMI was an independent predictor of CIMT (ß = 0.531, P < 0.001). CONCLUSION: Carotid artery structure and function were impaired in MHO, and improved carotid artery structure was associated with weight loss in MHO after bariatric surgery.

6.
BMC Oral Health ; 24(1): 591, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773498

RESUMO

BACKGROUND: Periodontitis can be avoided with a healthy lifestyle. However, studies have only looked at one lifestyle, ignoring the connection between lifestyle patterns and periodontitis. The purpose of this study was to look at the association between modifiable lifestyle patterns and periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey in 2009-2010 and 2011-2012. Smoke, drink, exercise, sleep duration, oral exams, and self-rated oral health were all lifestyle factors. The CDC/AAP classification/case definition was used to evaluate periodontitis. Drawing upon latent class analysis, distinct patterns of lifestyle were identified, with each participant exclusively affiliated with a single pattern. The association between lifestyle classes and periodontitis was then examined using ordinal logistic regression. RESULTS: 4686 (52%) of the total 9034 participants, with a mean age of 54.08, were women. Three lifestyle latent classes were found by fitting 2-10 models: "Class 1" (52%), " Class 2" (13%), and " Class 3" (35%). The "Class 1" displayed a prevalence of oral examination (75%), favorable self-rated oral health (92%), and engagement in physical activity (50%). The 'Class 2' exhibited the lowest alcohol consumption (64%) and smoking rates (73%) but the highest prevalence of physical inactivity (98%). The 'Class 3' showed a tendency for smoking (72%), alcohol consumption (78%), shorter sleep duration (50%), absence of oral examinations (75%), and suboptimal self-rated oral health (68%). The influencing variables for the latent classes of lifestyle were age, education, and poverty level. Periodontitis risk may rise by 24% for each additional unhealthy lifestyle practiced by participants (OR = 1.24, 95% CI: 1.18-1.31). The 'Class 3' (OR = 1.80, 95% CI: 1.52-2.13) had a greater risk of periodontitis compared to the 'Class 1'. CONCLUSIONS: Our analysis revealed that unhealthy lifestyle patterns are associated with periodontitis. These different lifestyle patterns need to be taken into account when developing public health interventions and clinical care.


Assuntos
Estilo de Vida , Inquéritos Nutricionais , Periodontite , Humanos , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Periodontite/epidemiologia , Estados Unidos/epidemiologia , Adulto , Fumar/epidemiologia , Exercício Físico , Consumo de Bebidas Alcoólicas/epidemiologia , Fatores de Risco , Idoso
7.
Clin Nucl Med ; 49(6): 569-571, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38598734

RESUMO

ABSTRACT: A 56-year-old man with metastatic lung adenocarcinoma received combined 177 Lu-FAP-2286 radiation therapy and targeted therapy. After 1 treatment cycle, improvement of symptoms and radiological remission was observed. Moreover, the patient did not report any adverse effects.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/radioterapia , Metástase Neoplásica , Lutécio , Adenocarcinoma/radioterapia , Adenocarcinoma/diagnóstico por imagem , Terapia de Alvo Molecular , Terapia Combinada
8.
Pharmaceutics ; 16(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38675141

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

9.
Clin Nucl Med ; 49(6): 505-512, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38498615

RESUMO

PURPOSE: We aimed to evaluate the efficacy and safety of 225 Ac-DOTATATE targeted α therapy (TAT) in various neuroendocrine neoplasms (NENs) with high somatostatin receptor (SSTR) expression. PATIENTS AND METHODS: This single-center prospective study included 10 patients with histologically diagnosed NENs that exhibited increased SSTR expression on 68 Ga-DOTATATE PET/CT imaging. All patients received 225 Ac-DOTATATE TAT. The primary end points were molecular imaging-based response and disease control rate (DCR), measured using the slightly modified Positron Emission Tomography Response Criteria in Solid Tumors 1.0. The secondary end points were adverse event profiles and clinical responses. The adverse event profile was determined according to the Common Terminology Criteria for Adverse Events version 5.0. Clinical response was assessed using the EORTC QLQ-C30 v3.0 (European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire version 3.0). RESULTS: A molecular imaging-based partial response was observed in 40% of all patients, SD in 40%, PD in 20%, and DCR in 80%. The DCR was 83.3% (5/6) in patients who were previously treated with 177 Lu-DOTATATE. According to the EORTC QLQ-C30 v3.0 score, most symptoms improved after 225 Ac-DOTATATE treatment, with only diarrhea showing no improvement. Grade III/IV hematological, kidney, and liver toxicities were not observed. The median follow-up time was 14 months (7-22 months), and no deaths were reported. CONCLUSIONS: This initial study suggests that 225 Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.


Assuntos
Tumores Neuroendócrinos , Octreotida , Compostos Organometálicos , Receptores de Somatostatina , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Receptores de Somatostatina/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Octreotida/análogos & derivados , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Compostos Organometálicos/efeitos adversos , Resultado do Tratamento , Adulto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Regulação Neoplásica da Expressão Gênica , Segurança , Estudos Prospectivos
10.
Bioresour Technol ; 399: 130575, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479629

RESUMO

Aerobic kitchen waste composting can contribute to greenhouse gas (GHGs) emissions and global warming. This study investigated the effects of biochar and zeolite on GHGs emissions during composting. The findings demonstrated that biochar could reduce N2O and CH4 cumulative releases by 47.7 %and 47.9 %, respectively, and zeolite could reduce the cumulative release of CO2 by 28.4 %. Meanwhile, the biochar and zeolite addition could reduce the abundance of potential core microorganisms associated with GHGs emissions. In addition, biochar and zeolite reduced N2O emissions by regulating the abundance of nitrogen conversion functional genes. Biochar and zeolite were shown to reduce the impact of bacterial communities on GHGs emissions. In summary, this study revealed that biochar and zeolite can effectively reduce GHG emissions during composting by altering the compost microenvironment and regulating microbial community structure. Such findings are valuable for facilitating high-quality resource recovery of organic solid waste.


Assuntos
Compostagem , Gases de Efeito Estufa , Zeolitas , Gases de Efeito Estufa/análise , Zeolitas/química , Solo/química , Metano/análise , Carvão Vegetal , Nitrogênio/análise , Óxido Nitroso/análise
11.
Clin Nucl Med ; 49(5): 472-474, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465996

RESUMO

ABSTRACT: A 57-year-old woman with a metastatic bone malignant solitary fibrous tumor received 177 Lu-FAP-2286 therapy. After 1 treatment cycle, 68 Ga-FAP-2286 PET/CT revealed remission of the lesions. Moreover, the patient did not report any adverse effects.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tumores Fibrosos Solitários , Feminino , Humanos , Pessoa de Meia-Idade , Radioisótopos , Radioisótopos de Gálio , Lutécio , Tumores Fibrosos Solitários/diagnóstico por imagem
12.
Radiol Med ; 129(5): 737-750, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38512625

RESUMO

PURPOSE: Breast cancer's impact necessitates refined diagnostic approaches. This study develops a nomogram using radiology quantitative features from contrast-enhanced cone-beam breast CT for accurate preoperative classification of benign and malignant breast tumors. MATERIAL AND METHODS: A retrospective study enrolled 234 females with breast tumors, split into training and test sets. Contrast-enhanced cone-beam breast CT-images were acquired using Koning Breast CT-1000. Quantitative assessment features were extracted via 3D-slicer software, identifying independent predictors. The nomogram was constructed to preoperative differentiation benign and malignant breast tumors. Calibration curve was used to assess whether the model showed favorable correspondence with pathological confirmation. Decision curve analysis confirmed the model's superiority. RESULTS: The study enrolled 234 female patients with a mean age of 50.2 years (SD ± 9.2). The training set had 164 patients (89 benign, 75 malignant), and the test set had 70 patients (29 benign, 41 malignant). The nomogram achieved excellent predictive performance in distinguishing benign and malignant breast lesions with an AUC of 0.940 (95% CI 0.900-0.940) in the training set and 0.970 (95% CI 0.940-0.970) in the test set. CONCLUSION: This study illustrates the effectiveness of quantitative radiology features derived from contrast-enhanced cone-beam breast CT in distinguishing between benign and malignant breast tumors. Incorporating these features into a nomogram-based diagnostic model allows for breast tumor diagnoses that are objective and possess good accuracy. The application of these insights could substantially increase reliability and efficacy in the management of breast tumors, offering enhanced diagnostic capability.


Assuntos
Neoplasias da Mama , Tomografia Computadorizada de Feixe Cônico , Meios de Contraste , Nomogramas , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada de Feixe Cônico/métodos , Estudos Retrospectivos , Diagnóstico Diferencial , Adulto , Idoso
13.
Aging (Albany NY) ; 16(4): 4014-4032, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38393698

RESUMO

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Citofagocitose , Prognóstico , Anticorpos , Nomogramas , Microambiente Tumoral
14.
World J Clin Cases ; 12(2): 405-411, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313643

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

15.
Biomolecules ; 14(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38397460

RESUMO

MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in the microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell line sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEV secretion. Target cell analysis suggested that the sEV miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEV miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Metástase Linfática , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Microambiente Tumoral
16.
BMC Nephrol ; 25(1): 47, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311719

RESUMO

BACKGROUND: Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD. METHODS: We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA). RESULTS: A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP. CONCLUSIONS: Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation. TRIAL REGISTRATION: CRD42023396704.


Assuntos
Anemia , Hematínicos , Isoquinolinas , Insuficiência Renal Crônica , Humanos , Anemia/tratamento farmacológico , Anemia/etiologia , Proteína C-Reativa , Doença Crônica , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Isoquinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
17.
J Environ Manage ; 351: 119952, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171126

RESUMO

Composting is an environmentally friendly method that facilitates the biodegradation of organic solid waste, ultimately transforming it into stable end-products suitable for various applications. The element iron (Fe) exhibits flexibility in form and valence. The typical Fe-related additives include zero-valent-iron, iron oxides, ferric and ferrous ion salts, which can be targeted to drive composting process through different mechanisms and are of keen interest to academics. Therefore, this review integrated relevant literature from recent years to provide more comprehensive overview about the influence and mechanisms of various Fe-related additives on composting process, including organic components conversion, humus formation and sequestration, changes in biological factors, stability and safety of composting end-products. Meanwhile, it was recommended that further research be conducted on the deep action mechanisms, biochemical pathways, budget balance analysis, products stability and application during organic solid waste composting with Fe-related additives. This review provided guidance for the subsequent targeted application of Fe-related additives in compost, thereby facilitating cost reduction and promoting circular economy objectives.


Assuntos
Compostagem , Resíduos Sólidos , Ferro , Solo , Biodegradação Ambiental , Compostos Ferrosos
18.
Pharmacol Res ; 200: 107062, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211637

RESUMO

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention. Especially, research on medicinal plant-derived extracellular vesicles (MPDEVs) are increasing, which are considered a kind of promising natural compound. This review summarizes current knowledge on MPDEVs in terms of bioactive compounds, including small RNA, protein, lipid, and metabolite, have been found on the surface and/or in the lumen of MPDEVs. Moreover, both in vitro and in vivo experiments have shown that MPDEVs exert broad biomedical functions, such as anti-inflammatory, anticancer, antioxidant, modulate microbiota, etc. MPDEVs may be a better substitute than animal-derived extracellular vesicles (ADEVs) because of safety and biocompatibility in the future.


Assuntos
Exossomos , Vesículas Extracelulares , Plantas Medicinais , Animais , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Comunicação Celular , RNA/metabolismo
19.
Clin Nucl Med ; 49(4): 338-339, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38049973

RESUMO

ABSTRACT: The treatment of metastatic pheochromocytoma is challenging. We report a case of a woman with recurrent pheochromocytoma with multiple metastases who achieved excellent response after 4 cycles of 177 Lu-DOTATATE therapy. She did not experience any observable adverse effects. Her disease was still stable 6 months after the fourth cycle of treatment.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Tomografia por Emissão de Pósitrons , Radioisótopos , Cintilografia , Feminino , Humanos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/radioterapia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/radioterapia , Lutécio
20.
J Clin Periodontol ; 51(1): 97-107, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850252

RESUMO

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.


Assuntos
Doenças Periodontais , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Estudos Transversais , Estudos Prospectivos , Biobanco do Reino Unido , Estudos de Coortes , Bancos de Espécimes Biológicos , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia
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