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1.
Int J Nanomedicine ; 19: 8159-8174, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139505

RESUMO

Background: Wound healing has always been a focal point in clinical work. Bacterial infections and immune microenvironment disorders can both hinder normal wound healing. Current wound dressings only serve a covering function. Developing wound dressings with antibacterial and immunomodulatory functions is crucial for aiding wound healing. To address this issue, we have developed a hydrogel with antibacterial and immunomodulatory functions for managing infected wounds. Methods: The present study describes a photo-crosslinked antibacterial hydrogel composed of curcumin, silver nanoparticles-loaded reduced graphene oxide, and silk fibroin methacryloyl for the treatment of infected wounds. The study assessed its antibacterial properties and its capacity to induce macrophage M2 polarization through in vitro and in vivo experiments. Results: The hydrogel demonstrates robust antibacterial properties and enhances macrophage M2 polarization in both in vitro and in vivo settings. Moreover, it accelerates the healing of infected wounds in vivo by stimulating collagen deposition and angiogenesis. Conclusion: Overall, this hydrogel shows great potential in managing wound infections.


Assuntos
Antibacterianos , Grafite , Hidrogéis , Nanopartículas Metálicas , Prata , Cicatrização , Infecção dos Ferimentos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Camundongos , Grafite/química , Grafite/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Curcumina/farmacologia , Curcumina/química , Macrófagos/efeitos dos fármacos , Fibroínas/química , Fibroínas/farmacologia , Células RAW 264.7 , Humanos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Masculino
2.
Biomed Res Int ; 2024: 8182887, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39140001

RESUMO

Despite the potential of neutralizing antibodies in the management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), clinical research on its efficacy in Chinese patients remains limited. This study is aimed at investigating the therapeutic effect of combination of antiviral therapy with neutralizing monoclonal antibodies for recurrent persistent SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion. A prospective study was conducted on Chinese patients who were treated with antiviral nirmatrelvir/ritonavir therapy and the neutralizing antibody tixagevimab-cilgavimab (tix-cil). The primary outcome was the rate of recurrent SARS-CoV-2 infection. Five patients with lymphoma experienced recurrent SARS-CoV-2 pneumonia and received tix-cil treatment. All patients had a history of CD20 monoclonal antibody use within the year preceding SARS-CoV-2 infection, and two patients also had a history of Bruton's tyrosine kinase (BTK) inhibitor use. These patients had notably low lymphocyte counts and exhibited near depletion of B cells. All five patients tested negative for serum SARS-CoV-2 IgG and IgM antibodies. None of the patients developed reinfection with SARS-CoV-2 pneumonia after antiviral and tix-cil treatment during the 6-month follow-up period. In conclusion, the administration of antiviral and SARS-CoV-2-neutralizing antibodies showed encouraging therapeutic efficacy against SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion, along with the potential preventive effect of neutralizing antibodies for up to 6 months.


Assuntos
Anticorpos Neutralizantes , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Linfoma , Ritonavir , SARS-CoV-2 , Humanos , Masculino , Anticorpos Neutralizantes/uso terapêutico , Pessoa de Meia-Idade , Feminino , Antivirais/uso terapêutico , SARS-CoV-2/imunologia , Linfoma/tratamento farmacológico , Linfoma/complicações , COVID-19/imunologia , COVID-19/complicações , Ritonavir/uso terapêutico , Idoso , Estudos Prospectivos , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Combinação de Medicamentos , Recidiva , Lopinavir/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico
3.
Asia Pac J Clin Nutr ; 33(3): 447-456, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38965732

RESUMO

BACKGROUND AND OBJECTIVES: Frailty has become a public health challenge in China. To investigate the association of foods consumption and physical activity with prefrailty and frailty among older Chinese adults in urban communities. METHODS AND STUDY DESIGN: In a cross-sectional study from February to July 2023, 1183 older adults aged between 65y-88y were enrolled from urban communities in Chongqing and Shandong province, China. Frailty Index (FI) was applied to measure prefrailty and frailty. Partial proportional odds model was used to assess the association between foods consumption, physical activity and prefrailty/frailty. RESULTS: Higher Dietary Diversity Score (DDS), (OR=0.61, 95% CI=0.46-0.80; OR=0.47, 95% CI=0.28-0.79), Consuming animal-based foods ≥2 times/day (OR=0.62, 95% CI=0.47-0.82; OR=0.54, 95% CI=0.33-0.88), soy products ≥2 times/week (OR=0.69, 95% CI=0.53-0.89; OR=0.51, 95% CI=0.31-0.84), fresh vegetables ≥2 times/day (OR=0.42, 95% CI=0.31-0.57; OR=0.41, 95% CI=0.23-0.72), and nuts ≥2 times/week (OR=0.71, 95% CI=0.55-0.91; OR=0.52, 95% CI=0.32-0.85) was associated with a lower risk of prefrailty and frailty. In addition, higher frequency and longer duration of walking (OR=0.61, 95% CI=0.42-0.88; OR=0.63, 95% CI=0.48-0.81), exercise (OR=0.48, 95% CI=0.35-0.64; OR=0.44, 95% CI=0.32-0.61) per week were significantly associated with lower risk of prefrailty. Furthermore, higher frequency and longer duration of walking (OR=0.42, 95% CI=0.25-0.72; OR=0.46, 95% CI=0.29-0.74), and housework (OR=0.39, 95% CI=0.24-0.65; OR=0.57, 95% CI=0.34-0.96) per week, were significantly associated with lower frailty. CONCLUSIONS: Higher DDS and higher frequency of animal-based foods, soy products, fresh vegetables, and nuts consumption is significantly associated with lower risk of prefrailty and frailty. Additionally, walking and exercising are significantly associated with lower risk of prefrailty, while walking and doing housework is significantly associated with lower frailty.


Assuntos
Dieta , Exercício Físico , Fragilidade , População Urbana , Humanos , Idoso , Estudos Transversais , Masculino , Feminino , China/epidemiologia , Fragilidade/epidemiologia , Idoso de 80 Anos ou mais , População Urbana/estatística & dados numéricos , Dieta/estatística & dados numéricos , Dieta/métodos , Idoso Fragilizado/estatística & dados numéricos , População do Leste Asiático
4.
Mol Ther Nucleic Acids ; 35(2): 102200, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38831898

RESUMO

Cancer-induced bone pain (CIBP) significantly impacts the quality of life and survival of patients with advanced cancer. Despite the established role of neurexins in synaptic structure and function, their involvement in sensory processing during injury has not been extensively studied. In this study using a rat model of CIBP, we observed increased neurexin 2 expression in spinal cord neurons. Knockdown of neurexin 2 in the spinal cord reversed CIBP-related behaviors, sensitization of spinal c-Fos neurons, and pain-related negative emotional behaviors. Additionally, increased acetylation of neurexin 2 mRNA was identified in the spinal dorsal horn of CIBP rats. Decreasing the expression of N-acetyltransferase 10 (NAT10) reduced neurexin 2 mRNA acetylation and neurexin 2 expression. In PC12 cells, we confirmed that neurexin 2 mRNA acetylation enhanced its stability, and neurexin 2 expression was regulated by NAT10. Finally, we discovered that the NAT10/ac4C-neurexin 2 axis modulated neuronal synaptogenesis. This study demonstrated that the NAT10/ac4C-mediated posttranscriptional modulation of neurexin 2 expression led to the remodeling of spinal synapses and the development of conscious hypersensitivity in CIBP rats. Therefore, targeting the epigenetic modification of neurexin 2 mRNA ac4C may offer a new therapeutic approach for the treatment of nociceptive hypersensitivity in CIBP.

5.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 61-65, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836683

RESUMO

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.


Assuntos
Osso e Ossos , Proteína C-Reativa , Fixadores Externos , Osteocalcina , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Osteocalcina/sangue , Osteocalcina/metabolismo , Pessoa de Meia-Idade , Osso e Ossos/metabolismo , Proteína C-Reativa/metabolismo , Fraturas Expostas/cirurgia , Fraturas Expostas/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Pró-Colágeno/sangue , Pró-Colágeno/metabolismo , Método Duplo-Cego , Colágeno Tipo I/metabolismo , Colágeno Tipo I/sangue , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Fragmentos de Peptídeos/sangue , Extremidades/cirurgia , Extremidades/lesões , Peptídeos , Hidrocortisona/sangue
6.
World J Urol ; 42(1): 285, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695883

RESUMO

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Idoso , Humanos , Masculino , Biópsia/métodos , Isótopos de Gálio , Radioisótopos de Gálio , Biópsia Guiada por Imagem/métodos , Nomogramas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Valor Preditivo dos Testes , Próstata/patologia , Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco
7.
Bioorg Chem ; 148: 107469, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781669

RESUMO

PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response. In this study, we reported the identification of a newly found PARP7 inhibitor (XLY-1) with higher inhibitory activity (IC50 = 0.6 nM) than that of RBN-2397 (IC50 = 6.0 nM). Additionally, XYL-1 displayed weak inhibitory activity on PARP1 (IC50 > 1.0 µM). Mechanism studies showed that XYL-1 could enhance the type Ⅰ interferon signaling in vitro. Pharmacodynamic experiments showed that 50 mg/kg XYL-1 could significantly inhibit tumor growth (TGI: 76.5 %) and related experiments showed that XYL-1 could restore type Ⅰ interferon signaling and promote T cell infiltration in tumor tissues. Taken together, XYL-1 shows promise as a potential candidate for developing cancer immunotherapy agents.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Imunoterapia , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos Endogâmicos BALB C
8.
Int J Orthop Trauma Nurs ; 54: 101096, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38599149

RESUMO

BACKGROUND: Hip fracture always requires hospitalization with high cost, which cause the complicated experiences and feelings. OBJECTIVE: To inform pre- and in-hospital communication practices between healthcare professionals and patients through a systematic review and qualitative research that synthesizes the experiences and feelings of older patients with hip fracture during the perioperative period. METHODS: We searched the Cochrane Library, PubMed, Web of Science, CINAHL, and three Chinese databases for relevant studies. Qualitative studies were included if they were related to the experiences and needs of hospitalization of older patients with hip fracture. Study quality was evaluated using the 2016 Joanna Briggs Institute quality evaluation criteria for qualitative research, and the results were consolidated using an thematic synthesis approach. RESULTS: Sixteen studies were included in our meta-synthesis. We extracted 58 clear research topics. Eight new categories were formed after induction and integration, which were finally merged into three integrated results. Integration result 1: Patients suffered a large amount of physical and psychological trauma. Integration result 2: A balance of proper protection and independence for patients is required. Integration result 3: Adequate pre-discharge preparation is required. CONCLUSIONS: Our review suggests that healthcare professionals should reduce pain catastrophizing and the fear of falling after surgery among older people with hip fracture. Furthermore, adequate pre-discharge preparation should be made jointly with patients. Meeting patients' diverse needs by various methods will promote active and healthy aging.

9.
Regen Biomater ; 11: rbae015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487713

RESUMO

The prognosis of glioblastoma (GBM) remains challenging, primarily due to the lack of a precise, effective imaging technique for comprehensively characterization. Addressing GBM diagnostic challenges, our study introduces an innovative dual-modal imaging that merges near-infrared (NIR) fluorescent imaging with magnetic resonance imaging (MRI). This method employs superparamagnetic iron oxide nanoparticles coated with NIR fluorescent dyes, specifically Cyanine 7, and targeted peptides. This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles, provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions, offering a comprehensive diagnostic tool for GBM. Notably, the probe traverses the blood-brain barrier, targeting GBM in vivo via peptides, producing clear and discernible images in both modalities. Cytotoxicity and histopathology assessments confirm the probe's favorable safety profile. These findings suggest that the dual-modal MR\NIR fluorescent imaging probe could revolutionize GBM prognosis and survival rates, which can also be extended to other tumors type.

10.
Ecotoxicol Environ Saf ; 274: 116203, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479313

RESUMO

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.


Assuntos
Poluentes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Adulto , Criança , Humanos , Resíduos Sólidos , Monitoramento Ambiental/métodos , Dibenzodioxinas Policloradas/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzofuranos , Poluentes Atmosféricos/análise , Incineração , Dioxinas/toxicidade , Medição de Risco , Dibenzofuranos Policlorados/análise , Solo
11.
Amino Acids ; 56(1): 19, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460031

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between dietary branched-chain amino acids (BCAAs) and the risk of developing hypertension. METHODS: A cohort study of 14,883 Chinese adults without hypertension at baseline with were followed for an average of 8.9 years. Dietary intakes of BCAAs, including Ile, Leu, and Val, were collected using 3-day 24-h meal recall and household condiment weighing. Cox proportional hazards regression, restricted cubic splines, interaction analysis, and sensitivity analysis were used to assess the relationship between dietary BCAAs and risk of developing self-reported hypertension, adjusting for age, gender, region, body mass index (BMI), smoking and drinking status, physical activity, energy intake, salt intake. RESULTS: Among 14,883 study subjects, 6386(42.9%) subjects aged ≥ 45 years at baseline, 2692 (18.1%) had new-onset hypertension during the study period, with a median age of 56 years. High levels of dietary BCAAs were associated with an increased risk of new-onset hypertension. Compared with the 41st-60th percentile, multivariable adjusted hazard ratio (HR) for new-onset hypertension was 1.16 (95% CI 1.01-1.32) for dietary BCAAs 61st-80th percentiles, 1.30 (1.13-1.50) for 81st-95th, 1.60 (1.32-1.95) for 96th-100th. The cut-off value of new-onset hypertension risk, total BCAAs, Ile, Leu, and Val were 15.7 g/day, 4.1 g/day, 6.9 g/day, 4.6 g/day, respectively, and the proportion of the population above these intake values were 13.9%, 13.1%, 15.4%, and 14.4%, respectively. Age, BMI, and salt intake had an interactive effect on this relationship (P < 0.001). CONCLUSION: There was a significant positive association between total dietary BCAAs, Ile, Leu, Val intake and the risk of developing hypertension, after adjustment for confounders. This relationship was influenced by age, BMI, and salt intake. Further research is needed to clarify the mechanism and potential role of BCAAs in the pathogenesis of hypertension.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Prospectivos , Aminoácidos de Cadeia Ramificada , Hipertensão/epidemiologia
12.
BMC Nephrol ; 25(1): 64, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395806

RESUMO

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-ß1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-ß1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-ß1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-ß1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-ß1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.


Assuntos
Óxidos N-Cíclicos , Insuficiência Renal Crônica , Marcadores de Spin , Fator de Crescimento Transformador beta1 , Animais , Ratos , Albuminas/química , Albuminas/metabolismo , Peso Corporal , Colágeno/metabolismo , Creatinina , Dieta , Fibrose , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Nefrectomia , NF-kappa B/metabolismo , Estresse Oxidativo , Insuficiência Renal Crônica/tratamento farmacológico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Biomarcadores , Sódio na Dieta/efeitos adversos
13.
J Med Chem ; 67(5): 4083-4099, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38348878

RESUMO

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized BMS-202 as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, X14 displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC50 = 15.73 nM). Furthermore, X14 exhibited good binding affinity to both human PD-L1 (KD = 14.62 nM) and mouse PD-L1 (KD = 392 nM). In particular, X14 showed favorable pharmacokinetic properties (oral bioavailability, F = 58.0%). In the 4T1 (mouse breast cancer cells) syngeneic mouse model, intragastric administration of X14 at 10 mg/kg displayed significant antitumor efficacy (TGI = 66%). Mechanistic investigations revealed that X14 effectively enhanced T-cell infiltration within the tumor microenvironment. Our study demonstrates that compound X14 exhibits potential as a candidate compound for the development of orally effective small-molecule inhibitors targeting PD-1/PD-L1.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Camundongos , Animais , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Imunoterapia , Neoplasias/terapia
14.
PeerJ ; 12: e16953, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406291

RESUMO

Background: Currently, bone marrow mesenchymal stem cells (BMSCs) have been reported to promote endometrial regeneration in rat models of mechanically injury-induced uterine adhesions (IUAs), but the therapeutic effects and mechanisms of hypoxic BMSC-derived exosomes on IUAs have not been elucidated. Objective: To investigate the potential mechanism by which the BMSCS-derived exosomal miR-424-5p regulates IUA angiogenesis through the DLL4/Notch signaling pathway under hypoxic conditions and promotes endometrial injury repair. Methods: The morphology of the exosomes was observed via transmission electron microscopy, and the expression of exosome markers (CD9, CD63, CD81, and HSP70) was detected via flow cytometry and Western blotting. The expression of angiogenesis-related genes (Ang1, Flk1, Vash1, and TSP1) was detected via RT‒qPCR, and the expression of DLL4/Notch signaling pathway-related proteins (DLL4, Notch1, and Notch2) was detected via Western blotting. Cell proliferation was detected by a CCK-8 assay, and angiogenesis was assessed via an angiogenesis assay. The expression of CD3 was detected by immunofluorescence. The endometrial lesions of IUA rats were observed via HE staining, and the expression of CD3 and VEGFA was detected via immunohistochemistry. Results: Compared with those in exosomes from normoxic conditions, miR-424-5p was more highly expressed in the exosomes from hypoxic BMSCs. Compared with those in normoxic BMSC-derived exosomes, the proliferation and angiogenesis of HUVECs were significantly enhanced after treatment with hypoxic BMSC-derived exosomes, and these effects were weakened after inhibition of miR-424-5p. miR-424-5p can target and negatively regulate the expression of DLL4, promote the expression of the proangiogenic genes Ang1 and Flk1, and inhibit the expression of the antiangiogenic genes Vash1 and TSP1. The effect of miR-424-5p can be reversed by overexpression of DLL4. In IUA rats, treatment with hypoxic BMSC exosomes and the miR-424-5p mimic promoted angiogenesis and improved endometrial damage. Conclusion: The hypoxic BMSC-derived exosomal miR-424-5p promoted angiogenesis and improved endometrial injury repair by regulating the DLL4/Notch signaling pathway, which provides a new idea for the treatment of IUAs.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Doenças Uterinas , Animais , Feminino , Ratos , Proteínas Adaptadoras de Transdução de Sinal/genética , Angiogênese , Proteínas de Ligação ao Cálcio/genética , Exossomos/genética , MicroRNAs/genética , Transdução de Sinais/genética , Doenças Uterinas/metabolismo
15.
J Bone Joint Surg Am ; 106(3): 218-226, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38113300

RESUMO

BACKGROUND: There is considerable debate regarding the longitudinal changes in overall rotator cuff (RC) muscle atrophy and intramuscular fatty infiltration (FI) following RC repair. We analyzed the longitudinal changes in overall 3D supraspinatus muscle volume and intramuscular FI (3D FI) to determine the effect of tear size and repair integrity on 3D muscle volume and intramuscular FI. METHODS: Forty-seven patients who underwent arthroscopic RC repair and had 6-point Dixon shoulder magnetic resonance imaging (MRI) preoperatively and 3 and 12 months postoperatively were enrolled. The 3D supraspinatus muscle volume and intramuscular FI were calculated at the 3 time points, and their changes over time were evaluated in the entire cohort as well as according to tear size and repair integrity. The agreement of the difference between time points among the patients was assessed by Bland-Altman analysis. RESULTS: In the cohort as a whole, there were no significant longitudinal changes in the 3D supraspinatus volume (19.65 ± 7.26 to 19.48 ± 7.46 cm 3 , p = 0.911) or 3D FI (17.18% ± 8.85% to 17.30% ± 9.18%, p = 0.977) from preoperatively to the final 12-month time point, overall and in the tear size and repair integrity subgroups. The 3D supraspinatus volume was significantly decreased at 3 months (17.39 ± 6.12 cm 3 , p < 0.001) but then increased again by 12 months (p < 0.001), reaching a value similar to the preoperative level. The 3D FI had a small increase at 3 months (18.18% ± 9.65%, p = 0.097) but subsequently decreased slightly again (p = 0.211), such that there were no significant longitudinal changes. The differences in the 3D supraspinatus volume and FI between these time points showed high agreement among patients. CONCLUSIONS: The overall 3D supraspinatus volume and 3D FI showed no longitudinal change between the preoperative baseline and the 12-month follow-up after arthroscopic RC repair. Tear size and repair integrity had no impact on the longitudinal patterns of muscle volume and intramuscular FI changes. The 3D supraspinatus volume decreased during the first 3 months but recovered to baseline at 12 months postoperatively; 3D FI was relatively stable throughout the 12 months of follow-up after repair. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Humanos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Artroscopia/métodos , Ombro , Imageamento por Ressonância Magnética , Ruptura
16.
ACS Biomater Sci Eng ; 10(1): 298-312, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38124374

RESUMO

Sonodynamic therapy is an emerging noninvasive tumor treatment method that utilizes ultrasound to stimulate sonosensitizers to produce a large amount of reactive oxygen species, inducing tumor cell death. Though sonodynamic therapy has very promising prospects in cancer treatment, the application of early organic sonosensitizers has been limited in efficacy due to the high blood clearance-rate, poor water solubility, and low stability. Inorganic sonosensitizers have thus been developed, among which piezoelectric semiconductor materials have received increasing attention in sonodynamic therapy due to their piezoelectric properties and strong stability. In this review, we summarized the designs, principles, modification strategies, and applications of several commonly used piezoelectric materials in sonodynamic therapy and prospected the future clinical applications for piezoelectric semiconductor materials in sonodynamic therapy.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanoestruturas/uso terapêutico
17.
Biosci. j. (Online) ; 34(6): 1724-1732, nov.-dec. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-968989

RESUMO

A total of 114 moderately halophilic bacteria were isolated from marine sediment environments. The isolates are belonged to 23 species based on the 16S rRNA sequence analysis. 63, 52, 47, 57, 74, 15 and 4 isolates are able to produce protease, amylase, lipase, pectinase, pulluanase, xylanase, cellulase, respectively. Combined hydrolytic enzyme activity analysis show that 15 strains present 1 hydrolytic activity, 32 strains present 2 hydrolytic activities, 21 strains present 3 hydrolytic activities, 26 strains present 4 hydrolytic activities, 11 strains present 5 hydrolytic activities and 2 strains present 6 hydrolytic activities. Hydrolase activities are widely distributed in a variety of species. The highest rates for production of protease, amylase, lipase, pectinase, pullanase, xylanase and cellulase were observed in species of B. baekryungensis, Hallobacillus sp., B. pumilus, B. megaterium or P. chungwhensis, B. amyloliquefaciens, B. pumilus, B. baekryungensis, respectively. However, the higher activities of protease, pectinase and pulluanase are frequently produced by the species of Halomonas sp. B. amyloliquefaciens or P. chungwhensis, and Vibrio sp. respectively. This investigation show that the diversity of halophilic bacteria from marine sediments could serve as a potential source of hydrolytic enzymes for industrial applications. (AU)


Um total de 114 bactérias moderadamente halofílicas foram isoladas de ambientes de sedimentos marinhos. Os isolados pertencem a 23 espécies com base na análise da sequência 16S rRNA. 63, 52, 47, 57, 74, 15 e 4 isolados são capazes de produzir protease, amilase, lipase, pectinase, pululanase, xilanase, celulase, respectivamente. A análise da atividade enzimática hidrolítica combinada mostra que 15 cepas apresentam 1 atividade hidrolítica, 32 cepas apresentam 2 atividades hidrolíticas, 21 cepas apresentam 3 atividades hidrolíticas, 26 cepas apresentam 4 atividades hidrolíticas, 11 cepas apresentam 5 atividades hidrolíticas e 2 cepas apresentam 6 atividades hidrolíticas. Atividades de hidrolase são amplamente distribuídas em uma variedade de espécies. As maiores taxas de produção de protease, amilase, lipase, pectinase, pululanase, xilanase e celulase foram observadas em espécies de B. baekryungensis, Hallobacillus sp., B. pumilus, B. megaterium ou P. chungwhensis, B. amyloliquefaciens, B. pumilus, B. baekryungensis, respectivamente. No entanto, as atividades mais elevadas de protease, pectinase e pululanase são freqüentemente produzidas pelas espécies de Halomonas sp. B. amyloliquefaciens ou P. chungwhensis e Vibrio sp. respectivamente. Esta investigação mostra que a diversidade de bactérias halofílicas de sedimentos marinhos pode servir como uma fonte potencial de enzimas hidrolíticas para aplicações industriais. (AU)


Assuntos
Microbiologia do Solo , Bactérias/enzimologia , Sedimentos Geológicos
18.
Acta cir. bras ; 33(6): 542-550, June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-949355

RESUMO

Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.


Assuntos
Animais , Masculino , Triglicerídeos/sangue , Calcitriol/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Valores de Referência , Glicemia/análise , Peso Corporal , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Regulação para Cima , Western Blotting , Reprodutibilidade dos Testes , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Receptores de Adiponectina/análise , Receptores de Adiponectina/efeitos dos fármacos , Lipase Lipoproteica/análise , Lipase Lipoproteica/efeitos dos fármacos
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