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1.
Bioorg Chem ; 151: 107701, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39154520

RESUMO

Four new diterpenoid tropolones, salvirrddones A-D (1-4), and four new icetexanes, salvirrddices A-D (9-12), along with thirteen new 11,12-seco-norabietane diterpenoids, salvirrddnor A-M (14-24, 31, 32) and sixteen known compounds (5-8, 13, 25-30, 33-37), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Their structures were elucidated by comprehensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Structurally, compounds 1-8 represent a class of rare natural products featuring a unique cyclohepta-2,4,6-trienone moiety with diterpenoid skeletons. Bioassays showed that only diterpenoid tropolones 3, 5, 6, and 7 exhibited significant activity against several human cancer cell lines with IC50 values ranging from 3.01 to 11.63 µM. Additionally, 3 was shown to inhibit Hep3B cell proliferation, block the G0/G1 phase of the cell cycle, induce mitochondrial dysfunction and oxidative stress, promote apoptosis, as well as inhibit migration and invasion in vitro. Meanwhile, 3 demonstrated anti-proliferative, pro-apoptotic, and migration-inhibitory effects in the Hep3B xenograft zebrafish model in vivo. Network pharmacological analysis and molecular docking results suggested that 3 may treat hepatocellular carcinoma (HCC) through the PI3K-Akt signaling pathway, as well as by binding PARP1 and CDK2 targets. Overall, the present results extremely expand the repertoire of diterpenoids from natural products and may provide a novel chemical scaffold for the discovery of new antitumor drugs.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Proliferação de Células , Diterpenos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Salvia , Peixe-Zebra , Humanos , Salvia/química , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Relação Estrutura-Atividade , Animais , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral
2.
Age Ageing ; 53(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108220

RESUMO

BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.


Assuntos
Demência , Osteoartrite , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/epidemiologia , Demência/epidemiologia , Demência Vascular/epidemiologia , Demência Vascular/diagnóstico , Incidência , Modelos Lineares , Imageamento por Ressonância Magnética , Osteoartrite/epidemiologia , Osteoartrite/terapia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Biobanco do Reino Unido , Reino Unido/epidemiologia
3.
Medicine (Baltimore) ; 103(31): e39203, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093766

RESUMO

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.


Assuntos
Anemia , Hemoglobinas , Isoquinolinas , Diálise Renal , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Anemia/tratamento farmacológico , Anemia/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Isoquinolinas/uso terapêutico , Isoquinolinas/efeitos adversos , Isoquinolinas/administração & dosagem , Hemoglobinas/análise , Hemoglobinas/metabolismo , Idoso , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Hematínicos/efeitos adversos , Hematínicos/administração & dosagem , Glicina/análogos & derivados , Glicina/uso terapêutico , Ferritinas/sangue , Resultado do Tratamento
4.
Front Immunol ; 15: 1405146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947338

RESUMO

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Aprendizado de Máquina , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Masculino , Feminino , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imunoterapia/métodos , Nomogramas , Resultado do Tratamento , Adulto , Radiômica
5.
Biosens Bioelectron ; 262: 116541, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38959719

RESUMO

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ferrocianetos , Ouro , Limite de Detecção , Estruturas Metalorgânicas , Neoplasias Ovarianas , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Técnicas Biossensoriais/métodos , Humanos , Estruturas Metalorgânicas/química , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Ferrocianetos/química , Técnicas Eletroquímicas/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Feminino , Ouro/química , Nanopartículas Metálicas/química , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Imunoensaio/métodos , Anticorpos Imobilizados/química , Nanocompostos/química
6.
Nat Prod Res ; : 1-8, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934460

RESUMO

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3-11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 µM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 µM, while other compounds showed low cytotoxic activity.

7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 715-719, 2024 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-38818556

RESUMO

OBJECTIVE: To explore the characteristics of SLCO1B1/SLCO1B3 gene variants among children with Rotor syndrome (RS). METHODS: Four children who were admitted to the Department of Hepatology of Hunan Children's Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1). RESULTS: Genetic testing has identified three variants of the SLCO1B1 gene, including c.1738C>T (p.R580*), c.757C>T (p.R253*) and c.1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c.481+22insLINE-1 and c.1747+1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. CONCLUSION: The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.


Assuntos
Testes Genéticos , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Humanos , Masculino , Feminino , Criança , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Pré-Escolar , Testes Genéticos/métodos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Sequenciamento do Exoma , Lactente , Mutação
8.
Clinics (Sao Paulo) ; 79: 100383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38797123

RESUMO

BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.


Assuntos
Biomarcadores , Colestase Intra-Hepática , Citrulinemia , Pró-Calcitonina , Curva ROC , Humanos , Pró-Calcitonina/sangue , Biomarcadores/sangue , Estudos Retrospectivos , Masculino , Feminino , Estudos de Casos e Controles , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/diagnóstico , Citrulinemia/sangue , Citrulinemia/complicações , Citrulinemia/diagnóstico , Lactente , Recém-Nascido , Sensibilidade e Especificidade , Proteína C-Reativa/análise , Valores de Referência
9.
Fitoterapia ; 175: 105954, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583638

RESUMO

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 µM.


Assuntos
Anti-Inflamatórios , Diterpenos , Glucosídeos , Óxido Nítrico , Compostos Fitoquímicos , Componentes Aéreos da Planta , Animais , Células RAW 264.7 , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Estrutura Molecular , Glucosídeos/farmacologia , Glucosídeos/isolamento & purificação , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química , China , Macrófagos/efeitos dos fármacos , Asteraceae/química , Sigesbeckia
10.
Abdom Radiol (NY) ; 49(8): 2902-2912, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38498153

RESUMO

PURPOSE: To compare urethral parameters between cystocele patients with and without stress urinary incontinence (SUI) and explore factors influencing SUI in cystocele patients via dynamic MRI. METHODS: The two-dimensional parameters evaluated included the paravaginal defects, levator ani muscle defects, urethral length, urethral funnel shape, bladder neck funnel width, bladder neck funnel depth, urethral angle, posterior vesicourethral angle, and anterior bladder protrusion. The three-dimensional parameters included the proximal urethra rotation angle, the distal urethra rotation angle, bladder neck mobility, urethral midpoint mobility, and external urethral meatus mobility. The independent samples t test was used for continuous variables, and the chi-square test was used for categorical variables. Binary logistic regression was used to identify factors independently associated with SUI in cystocele patients. RESULTS: The baseline parameters were similar between the 2 groups. Cystocele patients with SUI had a significantly higher point Aa (1.63 ± 1.06 cm vs. 0.81 ± 1.51 cm, p = 0.008); more anterior bladder protrusion (33.3% vs. 11.4%, p = 0.017); greater bladder neck mobility (36.38 ± 11.46 mm vs. 28.81 ± 11.72 mm, p = 0.005); mid-urethral mobility (22.94 ± 6.50 mm vs. 19.23 ± 6.65 mm, p = 0.014); and external urethral meatus mobility (22.42 ± 8.16 mm vs. 18.03 ± 8.51 mm, p = 0.022) than did cystocele patients without SUI. The other urethral parameters were similar in the groups (p > 0.05). Binary logistic regression showed that bladder neck mobility was independently associated with SUI in females with cystoceles (odds ratio, 1.06; 95% CI 1.015-1.107; p = 0.009). CONCLUSION: Cystocele patients with SUI have a higher point Aa, more anterior bladder protrusion, and greater urethral mobility than those without SUI. Bladder neck mobility is independently associated with SUI in females with cystoceles. REGISTRATION NUMBER: NCT03146195.


Assuntos
Cistocele , Imageamento por Ressonância Magnética , Uretra , Incontinência Urinária por Estresse , Humanos , Feminino , Cistocele/diagnóstico por imagem , Cistocele/complicações , Incontinência Urinária por Estresse/diagnóstico por imagem , Uretra/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso
11.
J Orthop Surg Res ; 19(1): 128, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326867

RESUMO

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.


Assuntos
MicroRNAs , Osteoporose , Humanos , Western Blotting , Proliferação de Células , MicroRNAs/genética , Osteoblastos , Osteoclastos , RNA Circular/genética
12.
Kaohsiung J Med Sci ; 40(4): 335-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38363110

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the role of HOXA transcript at the distal tip (HOTTIP) in its pathogenesis remains underexplored. This study investigates the mechanism by which HOTTIP influences apoptosis and the inflammatory response of fibroblast-like synoviocytes (FLS). An RA mouse model was established, and clinical scores were analyzed. Pathological changes in synovial tissues, bone mineral density (BMD) of the paws, serum tartrate-resistant acid phosphatase (TRAP) activity, and TNF-α and IL-1ß levels were assessed. FLS were transfected, and cell proliferation and apoptosis were examined. The RNA-pull-down assay determined HOTTIP's interaction with mixed-lineage leukemia 1 (MLL1), while RNA immunoprecipitation assay measured HOTTIP expression pulled down by MLL1. The levels of MLL1 and toll-like receptor 4 (TLR4) after MLL1 overexpression based on HOTTIP silencing were determined. Chromatin immunoprecipitation (ChIP) was performed with H3K4me3 as an antibody, followed by the evaluation of TLR4 expression. HOTTIP expression was elevated in RA mouse synovial tissues. Inhibition of HOTTIP led to reduced clinical scores, inflammatory infiltration, synovial hyperplasia, TRAP activity, and TNF-α and IL-1ß levels, along with increased BMD. In vitro Interference with HOTTIP suppressed RA-FLS apoptosis and inflammation. HOTTIP upregulated TLR4 expression by recruiting MLL1 to facilitate TLR4 promoter methylation. MLL1 overexpression reversed HOTTIP silencing-mediated repression of RA-FLS apoptosis. Activation of H3K4 methylation counteracted HOTTIP knockout, ameliorating the inflammatory response. HOTTIP regulates TLR4 expression by recruiting MLL1, leading to TLR4 promoter methylation, thereby suppressing RA-FLS proliferation and inducing cell apoptosis and inflammatory response in RA.


Assuntos
Artrite Reumatoide , Histona-Lisina N-Metiltransferase , Leucemia , RNA Longo não Codificante , Sinoviócitos , Receptor 4 Toll-Like , Animais , Camundongos , Apoptose/genética , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Proliferação de Células/genética , Células Cultivadas , Fibroblastos/patologia , Leucemia/metabolismo , Metilação , RNA Longo não Codificante/metabolismo , Sinoviócitos/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo
13.
ACS Omega ; 9(4): 4744-4753, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38313513

RESUMO

Imatinib (IMA) is a common chemotherapy drug for the treatment of leukemia and can potentially lead to drug resistance and toxicity during the course of treatment. Monitoring IMA concentrations in body fluids is necessary to optimize therapeutic schedules and avoid overdosage. In this paper, a novel ultrasensitive electrochemical sensor based on CuMOF and SWCNTs@AuNPs was developed to determine this antileukemic drug. Herein, AuNPs were supported on carboxylic single-walled carbon nanotubes (SWCNT-COOH), and then poly(diallyldimethylammonium chloride) (PDDA) was used as a dispersant to overcome the internal van der Waals interactions among the CNTs, further increasing the AuNP loading. Moreover, the morphology, structure, composition, and electrochemical properties of the CuMOF-SWCNTs@AuNPs composite film were characterized using SEM, TEM, FT-IR, UV-vis, XRD, XPS, CV, and EIS. Due to the advantage of the superior electrocatalytic and conductive properties of SWCNTs@AuNPs and their preferable adsorptivity and affinity to IMA of CuMOF, the fabricated glassy carbon electrode significantly improved the determination performance via their synergetic amplified effect. Under optimal conditions, a wide linear response was exhibited in the range from 0.05 to 20.0 µM and the low detection limit of 5.2 nM. In addition, our prepared sensor has been applied to the analysis of IMA in blood serum samples with acceptable results. Therefore, our CuMOF-SWCNTs@AuNPs-based electrochemical sensor possessed prominent sensing responses for IMA, which could be used as a prospective approach in clinical application.

14.
Clinics ; 79: 100383, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1564355

RESUMO

Abstract Background Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. Methods In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. Results There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. Conclusion PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

15.
Phytochemistry ; 218: 113958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154730

RESUMO

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.


Assuntos
Antineoplásicos , Sesquiterpenos Policíclicos , Salvia , Sesquiterpenos , Humanos , Células HeLa , Simulação de Acoplamento Molecular , Sesquiterpenos/química , Antineoplásicos/farmacologia , Salvia/química , Estrutura Molecular
16.
BMJ Open ; 13(12): e077974, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38101828

RESUMO

OBJECTIVES: Carcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS. DESIGN: We conducted a retrospective study in the Surveillance, Epidemiology and End Results (SEER) database (1975-2018) for primary CS. SETTING AND PARTICIPANTS: SEER database includes publicly available information from regional and state cancer registries in the US centres. A total of 5042 CS patients were identified. We selected the top five anatomic CS (uterus, double adnexa, lung, bladder and breast) patients for further analysis. PRIMARY OUTCOME MEASURES: Incidence was estimated by geographical region, age, sex, race, stage and primary site. Trends were calculated using joinpoint regression. The cancer-specific survival (CSS) rate and initial treatment were summarised. RESULTS: Nearly 80% of CS occurred in the uterus and double adnexa, followed by lung, bladder and breast. The elderly and black population presented the highest age-adjusted rate of CS. The rates of distant metastasis in CS progressively increased from 1989 to 2018. Atlanta was the area with the highest incidence at 0.7 per 100 000. Pulmonary and bladder CS more frequently occurred in men and were diagnosed with regional stage. Distant metastasis was mostly found in ovary/fallopian tube CS. Radiotherapy was more commonly applied in uterine CS, while adnexa CS cases were more likely to receive chemotherapy. Multiple treatments were more used in breast CS. Pulmonary CS seemed to suffer worse CSS (median: 9.92 months), for which radiotherapy might not provide survival benefits (HR 0.60, 95% CI 0.42 to 0.86). Compared with the common histological types in each site, CS had the shortest survival. CONCLUSIONS: CS has unique clinical features in each primary site. Substantial prognosis variances exist based on tumour locations. The aggressive course is the common feature in CS at all sites.


Assuntos
Carcinossarcoma , Sarcoma , Masculino , Feminino , Humanos , Idoso , Estudos Retrospectivos , Programa de SEER , Sistema de Registros , Prognóstico , Carcinossarcoma/epidemiologia , Carcinossarcoma/terapia
17.
World J Clin Cases ; 11(30): 7440-7449, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37969466

RESUMO

BACKGROUND: Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment. Pharmacogenomics can help guide individualized drug therapy and improve outcomes. CASE SUMMARY: We report a case of a preterm infant with multiple complications, including bronchopulmonary dysplasia (BPD), sepsis, intracranial hemorrhage, and hypertension. The infant was treated with various drugs, including dexamethasone and amlodipine. The infant was diagnosed with neonatal hypertension based on blood pressure measurements exceeding the 95th percentile for his age and sex. The possible causes of hypertension included dexamethasone, hydrochlorothiazide, spironolactone, and BPD. The infant was treated with oral amlodipine to lower his blood pressure. A pharmacogenomic test was performed to evaluate the genetic polymorphisms of ABCB1 and CYP3A5, which are involved in the metabolism and transport of dexamethasone and amlodipine. The infant's blood pressure was well controlled after the dose of amlodipine was reduced according to the pharmacogenomic results. The infant had a stable general condition and was discharged on the 100th d after birth. CONCLUSION: This case illustrates the importance of regular blood pressure monitoring and etiological investigation in preterm infants with hypertension. Pharmacogenomics can provide useful information for individualized drug therapy and safety in this population.

18.
Altern Ther Health Med ; 29(8): 512-517, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37652424

RESUMO

Background: Total hip arthroplasty (THA) has emerged as a pivotal approach for addressing femoral neck fractures (FNFs), a prevalent type of fracture in older people. Restoring joint functionality following surgery significantly contributes to patients' overall well-being. Therefore, the implementation of rational and effective rehabilitation exercises is crucial. Objective: This study aims to investigate the impact of phased rehabilitation management on patients with FNFs who have undergone THA. Methods: In this prospective comparative study, a total of 89 patients were enrolled. Among them, 49 patients underwent phased rehabilitation management, while 40 patients received conventional postoperative rehabilitation. The evaluation encompassed a range of assessments, including the Harris Hip Score (HHS) for the evaluation of hip joint function, the Five-Times-Sit-to-Stand Test (FTSST) to quantify lower limb muscle strength, the Barthel Index to assess activities of daily living, and the Visual Analog Scale (VAS) to measure pain intensity. Furthermore, preoperative and postoperative serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were diligently measured to provide a comprehensive understanding of the patient's inflammatory responses. Results: Overall, the study group exhibited a significantly higher average HHS after surgery compared to the control group. Notably, the VAS scores at 1 day and 3 days post-surgery in both groups demonstrated a reduced trend compared to preoperative values. This trend was more significant in the study group compared to the control group. The time taken for the FTSST in patients undergoing phased rehabilitation management was less compared to the control group. Furthermore, phased rehabilitation management was associated with more significant improvements in activities of daily living. Notably, IL-6 levels were higher in both the study and control groups at 1 day postoperatively than before surgery, while they decreased at 3 days postoperatively compared to the 1-day mark. The study group exhibited significantly lower levels of CRP (mg/L) and ESR (mm/h) compared to the control group. Conclusions: Implementing phased rehabilitation management for patients with FNFs following THA improves hip joint function, lower limb muscle strength, daily living activities, pain intensity, and inflammatory response.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Humanos , Idoso , Artroplastia de Quadril/reabilitação , Atividades Cotidianas , Estudos Prospectivos , Interleucina-6 , Resultado do Tratamento , Fraturas do Colo Femoral/cirurgia
19.
J Neurosurg Sci ; 67(2): 241-247, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35301841

RESUMO

INTRODUCTION: The aim of this meta-analysis was to evaluate the effects of acellular nerve grafts (ANGs) with bone marrow mesenchymal stem cells (BMSCs) or Schwann cells (SCs) on the treatment of sciatic nerve defect in rats. EVIDENCE ACQUISITION: Electronic databases were accessed to identify eligible targets. ANGs data were extracted for meta-analysis using Review Manager 5.3. EVIDENCE SYNTHESIS: The rats subjected to ANGs+BMSCs or ANGs+SCs are characterized by different sciatic nerve function index, nerve conduction, latency, amplitude, myelin sheath thickness, myelinated nerve fibers and gastrocnemius wet weight. accompanied with evidently superior recovery of limb function. These differences are of statistical significance (P<0.05) when compared to that of control group with ANGs only. CONCLUSIONS: ANGs with BMSCs or SCs can promote nerve regeneration and functional recovery in peripheral nerve defects.


Assuntos
Células-Tronco Mesenquimais , Células de Schwann , Ratos , Animais , Ratos Sprague-Dawley , Células de Schwann/transplante , Regeneração Nervosa/fisiologia , Nervo Isquiático
20.
J Biomater Appl ; 37(8): 1497-1506, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36469608

RESUMO

OBJECTIVES: To evaluate the effects of a modified porcine acellular dermal matrix (P-ADM), subepithelial connective tissue graft (SCTG) and other commercial bovine acellular dermal matrix membrane materials (B-ADM) on gingival soft tissue augmentation in the oral esthetic zone. MATERIAL AND METHODS: The characteristics of P-ADM were observed by scanning electron microscope (SEM), Hematoxylin and eosin (H&E) and Masson's trichrome staining (Masson staining). The biocompatibility of P-ADM was verified by CCK8, phalloidin and living/dead cell staining. Beagle dog models were constructed and the thickness of gingiva was analyzed by the intraoral scanner. The morphology was observed by H&E and Masson staining. RESULTS: Scanning electron microscopy, H&E and Masson staining showed that the P-ADM was mainly composed of collagen fibers, with no component of nuclear. The results of CCK8, phalloidin and living/dead cell staining indicated that the P-ADM had good cytocompatibility and no cytotoxicity. Human gingival fibroblasts were able to adhere and stretch on the surface of the material with pseudopodia. The SCTG group outperformed the B-ADM and P-ADM groups in terms of effectiveness, according to the analysis of digital oral scanning data at various time points following incremental soft tissue surgery. Compared with the B-ADM group, the effect of soft tissue increment was better in the P-ADM group. CONCLUSIONS: P-ADM, as a biocompatible biomaterial, can be used as an alternative biomaterial for oral soft tissue thickening. However, the results of this study need to be verified by more clinical trials.


Assuntos
Derme Acelular , Animais , Humanos , Bovinos , Suínos , Cães , Faloidina , Gengiva , Tecido Conjuntivo/transplante , Transplante de Pele/métodos
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