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1.
J Magn Reson Imaging ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602245

RESUMO

BACKGROUND: The detection rate of lung nodules has increased considerably with CT as the primary method of examination, and the repeated CT examinations at 3 months, 6 months or annually, based on nodule characteristics, have increased the radiation exposure of patients. So, it is urgent to explore a radiation-free MRI examination method that can effectively address the challenges posed by low proton density and magnetic field inhomogeneities. PURPOSE: To evaluate the potential of zero echo time (ZTE) MRI in lung nodule detection and lung CT screening reporting and data system (lung-RADS) classification, and to explore the value of ZTE-MRI in the assessment of lung nodules. STUDY TYPE: Prospective. POPULATION: 54 patients, including 21 men and 33 women. FIELD STRENGTH/SEQUENCE: Chest CT using a 16-slice scanner and ZTE-MRI at 3.0T based on fast gradient echo. ASSESSMENT: Nodule type (ground-glass nodules, part-solid nodules, and solid nodules), lung-RADS classification, and nodule diameter (manual measurement) on CT and ZTE-MRI images were recorded. STATISTICAL TESTS: The percent of concordant cases, Kappa value, intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman. The p-value <0.05 is considered significant. RESULTS: A total of 54 patients (age, 54.8 ± 11.9 years; 21 men) with 63 nodules were enrolled. Compared with CT, the total nodule detection rate of ZTE-MRI was 85.7%. The intermodality agreement of ZTE-MRI and CT lung nodules type evaluation was substantial (Kappa = 0.761), and the intermodality agreement of ZTE-MRI and CT lung-RADS classification was moderate (Kappa = 0.592). The diameter measurements between ZTE-MRI and CT showed no significant difference and demonstrated a high degree of interobserver (ICC = 0.997-0.999) and intermodality (ICC = 0.956-0.985) agreements. DATA CONCLUSION: The measurement of nodule diameter by pulmonary ZTE-MRI is similar to that by CT, but the ability of lung-RADS to classify nodes from MRI images still requires further research. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

2.
BMJ Open Respir Res ; 11(1)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580439

RESUMO

BACKGROUND: Despite substantial progress in reducing the global burden of chronic obstructive pulmonary disease (COPD), traditional methods to promote understanding and management of COPD are insufficient. We developed an innovative model based on the internet of things (IoT) for screening and management of COPD in primary healthcare (PHC). METHODS: Electronic questionnaire and IoT-based spirometer were used to screen residents. We defined individuals with a questionnaire score of 16 or higher as high-risk population, COPD was diagnosed according to 2021 Global Initiative for COPD (Global Initiative for Chronic Obstructive Lung Disease) criteria. High-risk individuals and COPD identified through the screening were included in the COPD PHC cohort study, which is a prospective, longitudinal observational study. We provide an overall description of the study's design framework and baseline data of participants. RESULTS: Between November 2021 and March 2023, 162 263 individuals aged over 18 from 18 cities in China were screened, of those 43 279 high-risk individuals and 6902 patients with COPD were enrolled in the cohort study. In the high-risk population, the proportion of smokers was higher than that in the screened population (57.6% vs 31.4%), the proportion of males was higher than females (71.1% vs 28.9%) and in people underweight than normal weight (57.1% vs 32.0%). The number of high-risk individuals increased with age, particularly after 50 years old (χ2=37 239.9, p<0.001). Female patients are more common exposed to household biofuels (χ2=72.684, p<0.05). The majority of patients have severe respiratory symptoms, indicated by a CAT score of ≥10 (85.8%) or an Modified Medical Research Council Dyspnoea Scale score of ≥2 (65.5%). CONCLUSION: Strategy based on IoT model help improve the detection rate of COPD in PHC. This cohort study has established a large clinical database that encompasses a wide range of demographic and relevant data of COPD and will provide invaluable resources for future research.


Assuntos
Internet das Coisas , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Coortes , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Atenção Primária à Saúde
3.
J Colloid Interface Sci ; 667: 529-542, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38653074

RESUMO

Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH)x) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH)x@PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH)x@PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H2S). Finally, CAT-Mn(SH)x@PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH)x@PMB-MNs. It exhibited enhanced enzyme and antioxidant activities, along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects. Hence,this study introduces a time-space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds.

4.
Int J Behav Nutr Phys Act ; 21(1): 42, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650004

RESUMO

BACKGROUND: Healthy lifestyle behaviors (LBs) have been widely recommended for the prevention and management of cardiovascular disease (CVD). Despite a large number of studies exploring the association between combined LBs and CVD, a notable gap exists in integration of relevant literatures. We conducted a systematic review and meta-analysis of prospective cohort studies to analyze the correlation between combined LBs and the occurrence of CVD, as well as to estimate the risk of various health complications in individuals already diagnosed with CVD. METHODS: Articles published up to February 10, 2023 were sourced through PubMed, EMBASE and Web of Science. Eligible prospective cohort studies that reported the relations of combined LBs with pre-determined outcomes were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using either a fixed or random-effects model. Subgroup analysis, meta-regression, publication bias, and sensitivity analysis were as well performed. RESULTS: In the general population, individuals with the healthiest combination of LBs exhibited a significant risk reduction of 58% for CVD and 55% for CVD mortality. For individuals diagnosed with CVD, adherence to the healthiest combination of LBs corresponded to a significant risk reduction of 62% for CVD recurrence and 67% for all-cause mortality, when compared to those with the least-healthy combination of LBs. In the analysis of dose-response relationship, for each increment of 1 healthy LB, there was a corresponding decrease in risk of 17% for CVD and 19% for CVD mortality within the general population. Similarly, among individuals diagnosed with CVD, each additional healthy LB was associated with a risk reduction of 27% for CVD recurrence and 27% for all-cause mortality. CONCLUSIONS: Adopting healthy LBs is associated with substantial risk reduction in CVD, CVD mortality, and adverse outcomes among individuals diagnosed with CVD. Rather than focusing solely on individual healthy LB, it is advisable to advocate for the adoption of multiple LBs for the prevention and management of CVD. TRIAL REGISTRATION: PROSPERO: CRD42023431731.


Assuntos
Doenças Cardiovasculares , Estilo de Vida , Humanos , Estudos Prospectivos , Prognóstico , Estilo de Vida Saudável , Comportamentos Relacionados com a Saúde , Exercício Físico , Fatores de Risco , Comportamento de Redução do Risco
5.
Front Microbiol ; 14: 1288920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029178

RESUMO

The effects of Helicobacter pylori eradication on gastric mucosa-colonizing microbes in patients with functional dyspepsia (FD) remain unclear. Here, we explored microbial variation induced by H. pylori infection and eradication treatment in FD patients. Gastric microbial abundance and diversity were significantly reduced in the H. pylori-infected FD patients. Eradication treatment increased alpha and beta diversity of gastric mucosa-colonizing microbes, and promoted the expansion of several probiotic microbes, such as Leuconostoc mesenteroides, which exhibited a matched antagonistic performance against H. pylori. Significant variation was observed in gastric mucosa-colonizing microbes between H. pylori-positive and H. pylori-negative FD patients. Eradication treatment induced microbial diversity recovery and may provide sufficient nutrition and space for probiotic microbes, such as Leuconostoc mesenteroides.

6.
Cell Commun Signal ; 21(1): 325, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957625

RESUMO

BACKGROUND: Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. METHODS: Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. RESULTS: Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. CONCLUSIONS: Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , RNA Citoplasmático Pequeno , Humanos , Lipídeos , Análise de Célula Única , Microambiente Tumoral
7.
FASEB J ; 37(12): e23284, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37905981

RESUMO

Cellular apoptosis is a central mechanism leveraged by chemotherapy to treat human cancers. 5-Methylcytosine (m5C) modifications installed on both DNA and mRNA are documented to regulate apoptosis independently. However, the interplay or crosstalk between them in cellular apoptosis has not yet been explored. Here, we reported that promoter methylation by DNMT1 coordinated with mRNA methylation by NSun2 to regulate osteosarcoma cell apoptosis. DNMT1 was induced during osteosarcoma cell apoptosis triggered by chemotherapeutic drugs, whereas NSun2 expression was suppressed. DNMT1 was found to repress NSun2 expression by methylating the NSun2 promoter. Moreover, DNMT1 and NSun2 regulate the anti-apoptotic genes AXL, NOTCH2, and YAP1 through DNA and mRNA methylation, respectively. Upon exposure to cisplatin or doxorubicin, DNMT1 elevation drastically reduced the expression of these anti-apoptotic genes via enhanced promoter methylation coupled with NSun2 ablation-mediated attenuation of mRNA methylation, thus rendering osteosarcoma cells to apoptosis. Collectively, our findings establish crosstalk of importance between DNA and RNA cytosine methylations in determining osteosarcoma resistance to apoptosis during chemotherapy, shedding new light on future treatment of osteosarcoma, and adding additional layers to the control of gene expression at different epigenetic levels.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Metilação , RNA Mensageiro/genética , Citosina , DNA , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Apoptose/genética
8.
Toxicol In Vitro ; 93: 105704, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769856

RESUMO

Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthole (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, the Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased the mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis, and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with the p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.


Assuntos
Cumarínicos , Sistema de Sinalização das MAP Quinases , Miócitos Cardíacos , Humanos , Apoptose , Autofagia , Cumarínicos/farmacologia , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Trastuzumab
9.
Open Life Sci ; 18(1): 20220681, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37589012

RESUMO

Bamboo charcoal, a type of manufactured biochar, is produced by pyrolyzing bamboo residue under anoxic conditions. Its beneficial properties in absorption, catalyst support, and agricultural function have attracted significant attention; however, relatively few studies have examined its effects on the soil microbiota. In this study, we analyzed the effects of bamboo charcoal on soil physicochemical properties, enzymes, and microbial community structure in tea plantations and investigated the optimal amount of bamboo charcoal to be added to organic fertilizer. The results show that bamboo charcoal can further increase soil available nitrogen, total and available phosphorus and potassium, organic carbon content, pH, and urease activity. However, only the combined use of bamboo charcoal and organic fertilizer significantly increased total nitrogen, sucrase, and ß-glucosidase activities in the soil. Bamboo charcoal also significantly increased the Chao1 and Shannon indices of microbiota diversity in a concentration-dependent manner. The structure of the bacterial community changed significantly after the bamboo charcoal addition, with Proteobacteria, Actinobacteria, and Firmicutes increasing and Acidobacteria decreasing. This study provides fundamental insights into the suitability of bamboo charcoal application for the ecological remediation of diseased soils.

10.
Food Chem ; 428: 136716, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37413835

RESUMO

Panax notoginseng is a world-renowned tonic herb, which has been used as a characteristic food in Southwest China for hundreds of years. However, the taste of Panax notoginseng is extremely bitter and serious after tasting, and its bitter components are unknown. This manuscript proposes a new strategy for discovering bitter components of Panax notoginseng based on the integrated analysis of pharmacophore model, system separation and bitter tracing technology. Firstly, 16 potential bitter components were obtained by UPLC-Q-Orbitrap HRMS combined with virtual screening, most of which were saponins.Then, the bitter components were further separated by system component separation and 5 potential bitter components were obtained. Finally, the main contributors of bitterness in Panax notoginseng were verified to be Ginsenoside Rg1, Ginsenoside Rb1 and Ginsenoside Rd by components knock-in and fNIRS. In general, this paper is the first literature report on the relatively systematic study of bitter components in Panax notoginseng.


Assuntos
Medicamentos de Ervas Chinesas , Ginsenosídeos , Panax notoginseng , Saponinas , Paladar , Farmacóforo , Ginsenosídeos/análise , Cromatografia Líquida de Alta Pressão
11.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2138-2145, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282902

RESUMO

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) µm to(37.91±0.42) µm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.


Assuntos
Tecnologia Farmacêutica , Tecnologia , Pós , Solubilidade , Extratos Vegetais , Tamanho da Partícula
12.
Neurosci Lett ; 809: 137298, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37196973

RESUMO

OBJECTIVE: The objective of this study is to explore the brain activity alterations in Parkinson's disease (PD) from the perspectives of neuronal activity, synchronization of neuronal activity, and coordination of whole-brain activity. METHODS: In this study, we recruited 38 PD patients and 35 matched healthy controls (HCs). We explored intrinsic brain activity alterations in PD by comparing resting-state functional magnetic resonance imaging (rs-fMRI) metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC). Two-sample t-tests were used to determine the differences between the two groups. Spearman correlation analysis was used to explore the relationships between abnormal ALFF, fALFF, PerAF, ReHo, and DC values and clinical indicators such as the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (H&Y) stage, and duration of disease. RESULTS: Compared with the HCs, PD had increased ALFF,fALFF, and PerAF in the temporal lobe and cerebellum, and decreased ALFF,fALFF, and PerAF in the occipital-parietal lobe in the neuronal activity. In the synchronization of neuronal activity, PD patients had increased ReHo in the right inferior parietal lobule and decreased ReHo in the caudate. In the coordination of whole-brain activity, PD patients had increased DC in the cerebellum and decreased DC in the occipital lobe. Correlation analysis showed that there is a correlation between abnormal brain regions and clinical indicators in PD. Notably, the changes in occipital lobe brain activity were found in ALFF, fALFF, PerAF, and DC, and were most correlated with the clinical indicators of PD patients. CONCLUSIONS: This study found that intrinsic brain function in several occipital-temporal-parietal and cerebellum regions was altered in PD patients, potentially related to the clinical indicators of PD. These results may enhance our understanding of the underlying neural mechanisms of PD and may contribute to further exploring the selection of therapeutic targets in PD patients.


Assuntos
Mapeamento Encefálico , Doença de Parkinson , Humanos , Mapeamento Encefálico/métodos , Doença de Parkinson/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cerebelo
13.
Cell Death Dis ; 14(2): 118, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781836

RESUMO

Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients' survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Proliferação de Células , 2-Naftilamina/uso terapêutico , Linhagem Celular Tumoral , Apoptose , Quinases Associadas a rho
15.
BMC Med Imaging ; 22(1): 209, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447133

RESUMO

OBJECTIVE: To explore the characteristics of peripheral blood, high resolution computed tomography (HRCT) imaging and the radiomics signature (RadScore) in patients infected with delta variant virus under different coronavirus disease (COVID-19) vaccination status. METHODS: 123 patients with delta variant virus infection collected from November 1, 2021 to March 1, 2022 were analyzed retrospectively. According to COVID-19 vaccination Status, they were divided into three groups: Unvaccinated group, partially vaccinated group and full vaccination group. The peripheral blood, chest HRCT manifestations and RadScore of each group were analyzed and compared. RESULTS: The mean lymphocyte count 1.22 ± 0.49 × 10^9/L, CT score 7.29 ± 3.48, RadScore 0.75 ± 0.63 in the unvaccinated group; The mean lymphocyte count 1.55 ± 0.70 × 10^9/L, CT score 5.27 ± 2.72, RadScore 1.03 ± 0.46 in the partially vaccinated group; The mean lymphocyte count 1.87 ± 0.70 × 10^9/L, CT score 3.59 ± 3.14, RadScore 1.23 ± 0.29 in the fully vaccinated group. There were significant differences in lymphocyte count, CT score and RadScore among the three groups (all p < 0.05); Compared with the other two groups, the lung lesions in the unvaccinated group were more involved in multiple lobes, of which 26 cases involved the whole lung. CONCLUSIONS: Through the analysis of clinical features, pulmonary imaging features and radiomics, we confirmed the positive effect of COVID-19 vaccine on pulmonary inflammatory symptoms and lymphocyte count (immune system) during delta mutant infection.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Vacinação
16.
Mol Pharm ; 19(9): 3007-3025, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35848076

RESUMO

Orodispersible dosage forms, characterized as quick dissolving and swallowing without water, have recently gained great attention from the pharmaceutical industry, as these forms can satisfy the needs of children, the elderly, and patients suffering from mental illnesses. However, poor taste by thorough exposure of the drugs' dissolution in the oral cavity hinders the effectiveness of the orodispersible dosage forms. To bridge this gap, we put forward three taste-masking strategies with respect to the intensity of time, concentration, and perception. We further investigated the raw material processing, the composition of auxiliary material, formulation techniques, and process control in each strategy and drew conclusions about their effects on taste masking.


Assuntos
Percepção , Paladar , Administração Oral , Idoso , Criança , Formas de Dosagem , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Solubilidade
17.
Int J Biol Sci ; 18(7): 2882-2897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541895

RESUMO

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.


Assuntos
Cardiotoxicidade , Doxorrubicina , Encefalina Metionina , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Proliferação de Células , Doxorrubicina/toxicidade , Encefalina Metionina/metabolismo , Encefalina Metionina/farmacologia , Humanos , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteínas de Ligação a RNA/genética
18.
Transfus Med Hemother ; 49(6): 346-357, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36654975

RESUMO

Background: Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals. Methods: Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix. Results: We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found. Conclusion: These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.

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