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1.
Neurol Sci ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38653915

RESUMO

OBJECTIVE: To analyze the local functional activity and connectivity features of the brain associated with drug response inpatients newly diagnosed with epilepsy (NDE) who are naïve to anti-seizure medication (ASM). METHODS: Recruited patients, underwent functional magnetic resonance imaging at baseline, and were assigned to the well-controlled (WC, n = 28) or uncontrolled (UC, n = 11) groups based on their response to ASM. Healthy participants were included in the control group (HC, n = 29). The amplitudes of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were used to measure local functional activity, and voxel-wise degree centrality (DC) and seed-based functional connectivity (FC) were used to evaluate the connecting intensity of the brain areas. RESULTS: Compared to the HC and WC groups, the UC group had higher ALFF values in the left posterior central gyrus (PoCG.L) and left inferior temporal gyrus (ITG.L) and higher DC in the bilateral PoCG (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). Both PoCG and ITG.L in the UC group showed stronger FC with multiple brain regions, mainly located in the occipital and temporal lobes, compared to the HC or WC group, while the WC group showed decreased or similar FC compared to the HC group. INTERPRETATION: Excessive enhancement of brain functional activity or connecting intensity in ASM-naïve patients with NDE may be associated with a higher risk of poor drug response.

2.
Arch Gynecol Obstet ; 310(1): 103-111, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342828

RESUMO

OBJECTIVE: Although human umbilical cord-derived mesenchymal stem cells (HU-MSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing, the underlying molecular mechanisms have been poorly understood. It has been shown that the TGF-ß/Smad signaling pathway plays an important role in the process of scar formation. The present study focused on exploring whether HU-MSCs improve uterine incision healing after cesarean delivery in rats via the TGF-ß/Smad signaling pathway. STUDY DESIGN: Pregnant rats were randomly assigned to three groups, including the NP group, incision-injected group (HU-MSCs1 group), and tail vein-injected group (HU-MSCs2 group), and 30 days after cesarean section, sampling was carried out to further explore the specific mechanisms from tissue and protein levels. RESULTS: HU-MSCs secretion could inhibit the fibrosis of scar tissue. We observed that the TGF-ß induced expression of TGF-ß1, Smad2, and Smad3 was attenuated upon HU-MSCs treatment in scar tissue, while the decrease in TGF-ß3 expression was enhanced by HU-MSCs. Furthermore, HU-MSCs treatment accelerated wound healing and attenuated collagen deposition in a damaged uterine rat model, leading to the promoting of uterine incision scarring. In addition, the expression of alpha-smooth muscle actin (a-SMA) was enhanced by HU-MSCs treatment. CONCLUSION: HU-MSCs transplantation promotes rat cesarean section uterine incision scar healing by modulating the TGF-ß/Smad signaling pathway.


Assuntos
Cesárea , Cicatriz , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Transdução de Sinais , Cordão Umbilical , Cicatrização , Animais , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos , Gravidez , Cordão Umbilical/citologia , Humanos , Cicatriz/metabolismo , Ratos Sprague-Dawley , Útero/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteína Smad3/metabolismo , Proteína Smad2/metabolismo
3.
Pak J Med Sci ; 40(3Part-II): 326-331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356823

RESUMO

Objective: Gestational diabetes mellitus (GDM) seriously influences the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, our study planned to probe the correlation between serum microRNA-122 and VEGF expression and pregnancy outcome in GDM patients. Methods: This was a retrospective study of the correlation between serum microRNA-122 and vascular endothelial growth factor (VEGF) expression and pregnancy outcome in GDM patients. Sixty GDM patients admitted to the Fourth Hospital of Shijiazhuang from January 2021 to October 2022 were included in the research group (RG), and another 60 healthy pregnant women were included in the control group (CG). Serum miR-122 and VEGF levels were quantified using quantitative real-time polymerase chain reaction. The value of miR-122 and VEGF in predicting adverse pregnancy outcomes was analyzed by receiver operating characteristic curve. Results: Serum miR-122 and VEGF levels in the RG were higher relative to the CG. The total occurrence of adverse pregnancy outcomes in the RG was higher relative to the CG (P<0.05). Serum miR-122 together with VEGF levels in the poor outcome group was higher relative to the good outcome group (P<0.05). ROC analysis revealed that miR-122 and VEGF could be used to predict adverse pregnancy outcome (P<0.0001). The area under the curve of miR-122 was 0.860, 95% confidence interval (CI) =0.793-0.926, and the area under the curve of VEGF was 0.780, 95% CI =0.694-0.866. Serum levels of miR-122, VEGF were positively related with abortion, preterm delivery, low birth weight infants, macrogenesis infants, and fetal development abnormalities (P<0.001). Conclusion: The higher serum miR-122 and VEGF levels in GDM patients with satisfactory blood glucose control, the greater the probability of adverse pregnancy outcome, which should be paid attention to by clinicians.

4.
Seizure ; 120: 72-82, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908144

RESUMO

PURPOSE: This systematic review and meta-analysis examined the risk factors for suicide-related events (SRE) in patients with epilepsy (PWE). METHODS: The PubMed, Embase, Cochrane Online Library, and ClinicalTrials.gov databases were searched for relevant articles published from 1946 to August 30, 2022. The quality of the extracted articles was assessed using the Newcastle-Ottawa scale. Subsequently, a meta-analysis of PWE was performed to calculate the random-effects pooled odds ratios (ORs) for studies investigating the association between suicide and its associated risk factors. All statistical analyses were performed using R version 4.1.0. RESULTS: A total of 2,803 studies were screened, of which 23 articles comprising 6,723 PWE were included in our meta-analysis. Female sex (odds ratio [OR]=1.24, 95 % confidence interval [CI]: 1.08-1.43), low quality of life (QOL) scores (standardized mean difference [SMD]= -0.89, CI: -1.17 - -0.61), poor social support (OR=3.44, CI: 1.83-6.46), unemployment (OR=1.82, CI: 1.40-2.38), unmarried status (OR=1.48, CI: 1.12-1.97), low income (OR=1.37, CI: 1.07-1.76), low education (OR=1.33, CI: 1.04-1.68), use of antidepressant drugs (OR=7.77, CI: 3.17-19.03), uncontrolled seizures (OR=2.28, CI: 1.63-3.18), use of multiple antiepileptic drugs (OR=1.70, CI: 1.33-2.18), early age at onset of epilepsy (SMD= -0.15, CI: -0.30 - -0.0002), depression (OR=6.85, CI: 4.88-9.62), and anxiety (OR=3.76, CI: 2.92-4.84) were identified as significant risk factors of SRE. SIGNIFICANCE: There are many risk factors for SRE in PWE, as outlined above. Interventions targeting these risk factors may help reduce the risk of SRE in PWE.


Assuntos
Epilepsia , Suicídio , Humanos , Epilepsia/epidemiologia , Epilepsia/psicologia , Fatores de Risco , Suicídio/estatística & dados numéricos , Suicídio/psicologia
5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 529-534, 2024 May 15.
Artigo em Zh | MEDLINE | ID: mdl-38752237

RESUMO

Objective: To evaluate the safety and effectiveness of applying self-stabilizing zero-profile three-dimensional (3D) printed artificial vertebral bodies in anterior cervical corpectomy and fusion (ACCF) for cervical spondylotic myelopathy. Methods: A retrospective analysis was conducted on 37 patients diagnosed with cervical spondylotic myelopathy who underwent single-level ACCF using either self-stabilizing zero-profile 3D-printed artificial vertebral bodies ( n=15, treatment group) or conventional 3D-printed artificial vertebral bodies with titanium plates ( n=22, control group) between January 2022 and February 2023. There was no significant difference in age, gender, lesion segment, disease duration, and preoperative Japanese Orthopedic Association (JOA) score between the two groups ( P>0.05). Operation time, intraoperative bleeding volume, hospitalization costs, JOA score and improvement rate, incidence of postoperative prosthesis subsidence, and interbody fusion were recorded and compared between the two groups. Results: Compared with the control group, the treatment group had significantly shorter operation time and lower hospitalization costs ( P<0.05); there was no significant difference in intraoperative bleeding volume between the two groups ( P>0.05). All patients were followed up, with a follow-up period of 6-21 months in the treatment group (mean, 13.7 months) and 6-19 months in the control group (mean, 12.7 months). No dysphagia occurred in the treatment group, while 5 cases occurred in the control group, with a significant difference in the incidence of dysphagia between the two groups ( P<0.05). At 12 months after operation, both groups showed improvement in JOA scores compared to preoperative scores, with significant differences ( P<0.05); however, there was no significant difference in the JOA scores and improvement rate between the two groups ( P>0.05). Radiographic examinations showed the interbody fusion in both groups, and the difference in the time of interbody fusion was not significant ( P>0.05). At last follow-up, 2 cases in the treatment group and 3 cases in the control group experienced prosthesis subsidence, with no significant difference in the incidence of prosthesis subsidence ( P>0.05). There was no implant displacement or plate-screw fracture during follow-up. Conclusion: The use of self-stabilizing zero-profile 3D-printed artificial vertebral bodies in the treatment of cervical spondylotic myelopathy not only achieves similar effectiveness to 3D-printed artificial vertebral bodies, but also reduces operation time and the incidence of postoperative dysphagia.


Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Impressão Tridimensional , Fusão Vertebral , Espondilose , Humanos , Espondilose/cirurgia , Vértebras Cervicais/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Masculino , Descompressão Cirúrgica/métodos , Feminino , Resultado do Tratamento , Placas Ósseas , Corpo Vertebral/cirurgia , Doenças da Medula Espinal/cirurgia , Pessoa de Meia-Idade
6.
Eur J Med Res ; 29(1): 322, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858682

RESUMO

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals' social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic-environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.


Assuntos
Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/terapia , Qualidade de Vida , Medicina de Precisão/métodos
7.
Zhongguo Gu Shang ; 37(2): 153-8, 2024 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-38425066

RESUMO

OBJECTIVE: To explore the potential value of three-dimensional fast spin echo(3D-SPACE) combined with multilayer spiral CT (MSCT) in the diagnosis of knee cruciate ligament injury, to provide a new direction for the optimization of subsequent clinical diagnosis. METHODS: A total of 120 patients with knee cruciate ligament injury were treated from April 2020 to April 2021, aged from 21 to 68 with an average of(41.52±4.13) years old. For all patients, separate MSCT scanner scans, 3D-SPACE sequence scans alone and 3D-SPACE sequence combined with MSCT scans were used. The injury and classification of the anterior and posterior cruciate ligament of the knee were compared, the length of the anterior-medial bundle and posterolateral bundle and its angle of the knee with the horizontal plane were observed, the diagnostic value of 3 diagnostic methods in knee cruciate ligament injury were determined. RESULTS: There was no significant difference between the 3D-SPACE sequence scan alone and the MSCT test alone on the total diagnostic rate and grading total diagnostic rate(P>0.05). The total diagnostic rate and grading total diagnostic rate of 3D-SPACE scan combined with MSCT were significantly higher than those of 3D-SPACE scan or MSCT alone(P<0.05). The 3D-SPACE sequence scan alone and the MSCT detection alone had no significant difference in the measurement values related to the anterior and posterior cruciate ligaments of the knee joint(P>0.05). 3D-SPACE sequence scanning combined with MSCT detection on the knee joint anterior and posterior cruciate ligament related measurements were significantly higher than the 3D-SPACE sequence scan or MSCT detection alone(P<0.05). The area under the ROC curve estimated by 3D-SPACE sequence scanning combined with MSCT was 0.960, which was significantly higher than that of 3D-SPACE sequence scanning and MSCT alone evaluating the area under the ROC curve line of 0.756 and 0.795. The combined 3D-SPACE sequence scanning and 3D-SPACE sequence scanning MSCT analysis and prediction models were statistically different(Z=2.236, P<0.05), and MSCT alone and 3D-SPACE sequence scanning combined with MSCT analysis and prediction models were statistically different(Z=2.653, P<0.05). CONCLUSION: The application of 3D-SPACE sequence combined with MSCT scanning for knee cruciate ligament injury can improve the diagnosis rate of patients with knee cruciate ligament injury.It can be used as a diagnostic tool for patients with knee cruciate ligament injury and is worthy of clinical application.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Ligamento Cruzado Posterior , Lesões dos Tecidos Moles , Humanos , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Artroscopia , Traumatismos do Joelho/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Ligamento Cruzado Posterior/lesões , Tomografia Computadorizada Espiral , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem
8.
Biomed Pharmacother ; 175: 116627, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653112

RESUMO

Nanoparticles (NPs) serve as versatile delivery systems for anticancer, antibacterial, and antioxidant agents. The manipulation of protein-NP interactions within biological systems is crucial to the application of NPs in drug delivery and cancer nanotherapeutics. The protein corona (PC) that forms on the surface of NPs is the interface between biomacromolecules and NPs and significantly influences their pharmacokinetics and pharmacodynamics. Upon encountering proteins, NPs undergo surface alterations that facilitate their clearance from circulation by the mononuclear phagocytic system (MPS). PC behavior depends largely on the biological microenvironment and the physicochemical properties of the NPs. This review describes various strategies employed to engineer PC compositions on NP surfaces. The effects of NP characteristics such as size, shape, surface modification and protein precoating on PC performance were explored. In addition, this study addresses these challenges and guides the future directions of this evolving field.


Assuntos
Nanopartículas , Coroa de Proteína , Coroa de Proteína/metabolismo , Coroa de Proteína/química , Humanos , Animais , Sistemas de Liberação de Medicamentos/métodos , Engenharia de Proteínas/métodos , Propriedades de Superfície
9.
Eur J Pharmacol ; 966: 176348, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38286356

RESUMO

Rhubarb free anthraquinones (RhA) have significant lipid-regulating activity. However, whether RhA monomers have a role in lipid-regulating and their mechanism of action remains unclear. Based on the cholesterol accumulated HepG2 cell model, the cholesterol-regulating effect of RhA monomers and their combinations was investigated. The expression of sterol-regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) of the model cells was analyzed to preliminarily explore the mechanism of action. After that, the liposomes of each active RhA monomer were separately prepared with the same lipid materials and the same preparation method so that each monomer has similar or equal bioavailability after oral administration to rats. Finally, the hypercholesterolemic rat model was established, and the effect of active RhA monomers loaded liposomes as well as their combinations on cholesterol-regulating was investigated and their mechanism of action was analyzed. The results showed that aloe-emodin, rhein and emodin were the main cholesterol-regulating components of RhA, and the combination of rhein and emodin showed significant cholesterol-lowering effect, which may be related to the expression of SREBP2, HMGCR and SQLE in the rat liver.


Assuntos
Emodina , Rheum , Ratos , Animais , Ratos Sprague-Dawley , Lipossomos , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Lipídeos
10.
Artigo em Inglês | MEDLINE | ID: mdl-38775884

RESUMO

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

11.
Medicine (Baltimore) ; 103(21): e38260, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788026

RESUMO

Preeclampsia (PE) is a pregnancy complication characterized by placental dysfunction. However, the relationship between maternal blood markers and PE is unclear. It is helpful to improve the diagnosis and treatment of PE using new biomarkers related to PE in the blood. Three PE-related microarray datasets were obtained from the Gene Expression Synthesis database. The limma software package was used to identify differentially expressed genes (DEGs) between PE and control groups. Least absolute shrinkage and selection operator regression, support vector machine, random forest, and multivariate logistic regression analyses were used to determine key diagnostic biomarkers, which were verified using clinical samples. Subsequently, functional enrichment analysis was performed. In addition, the datasets were combined for immune cell infiltration analysis and to determine their relationships with core diagnostic biomarkers. The diagnostic performance of key genes was evaluated using the receiver operating characteristic (ROC) curve, C-index, and GiViTi calibration band. Genes with potential clinical applications were evaluated using decision curve analysis (DCA). Seventeen DEGs were identified, and 6 key genes (FN1, MYADM, CA6, PADI4, SLC4A10, and PPP4R1L) were obtained using 3 types of machine learning methods and logistic regression. High diagnostic performance was found for PE through evaluation of the ROC, C-index, GiViti calibration band, and DCA. The 2 types of immune cells (M0 macrophages and activated mast cells) were significantly different between patients with PE and controls. All of these genes except SLC4A10 showed significant differences in expression levels between the 2 groups using quantitative reverse transcription-polymerase chain reaction. This model used 6 maternal blood markers to predict the occurrence of PE. The findings may stimulate ideas for the treatment and prevention of PE.


Assuntos
Biomarcadores , Biologia Computacional , Pré-Eclâmpsia , Humanos , Feminino , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/imunologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Gravidez , Biologia Computacional/métodos , Biomarcadores/sangue , Curva ROC , Adulto , Perfilação da Expressão Gênica/métodos
12.
J Agric Food Chem ; 72(17): 9567-9580, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38627202

RESUMO

Monascus is a filamentous fungus that has been used in the food and pharmaceutical industries. When used as an auxiliary fermenting agent in the manufacturing of cheese, Monascus cheese is obtained. Citrinin (CIT) is a well-known hepatorenal toxin produced by Monascus that can harm the kidneys structurally and functionally and is frequently found in foods. However, CIT contamination in Monascus cheese is exacerbated by the metabolic ability of Monascus to product CIT, which is not lost during fermentation, and by the threat of contamination by Penicillium spp. that may be introduced during production and processing. Considering the safety of consumption and subsequent industrial development, the CIT contamination of Monascus cheese products needs to be addressed. This review aimed to examine its occurrence in Monascus cheese, risk implications, traditional control strategies, and new research advances in prevention and control to guide the application of biotechnology in the control of CIT contamination, providing more possibilities for the application of Monascus in the cheese industry.


Assuntos
Queijo , Citrinina , Contaminação de Alimentos , Monascus , Monascus/metabolismo , Monascus/química , Queijo/microbiologia , Queijo/análise , Citrinina/análise , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Humanos , Fermentação
13.
Biomater Sci ; 12(3): 691-709, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38099460

RESUMO

Presently, the commonly used anti-tumor drugs lack targeting ability, resulting in a limited therapeutic efficacy and significant side effects. In this view, platelet membranes (PMs) not only exhibit specific binding of its P-selectin protein with CD44, which is highly expressed on breast cancer cells, to promote tumor-active targeting by PM biomimetic nanoplatforms, but also respond to vascular damage, thus inducing biochemotactic targeting to further facilitate the aggregation of these nanoplatforms. Therefore, in this study, a PM was applied to construct a biochemotactic-targeting nanotherapeutic platform based on dendritic large pore mesoporous silica nanoparticles (DLMSNs) co-loaded with chlorin e6 (Ce6) and lapatinib (LAP) to achieve the combination of photodynamic therapy (PDT) and EGFR inhibition therapy for breast cancer. Under laser irradiation, PM@DLMSN/Ce6/Lap could not only effectively kill breast tumor cells by the PDT, but also damage blood vessels. By combining the EGFR inhibition of LAP, PM@DLMSN/Ce6/Lap could better inhibit the migration and movement of tumor cells. In vitro and in vivo results showed that PM@DLMSN/Ce6/Lap could achieve active-targeting drug delivery to breast tumors and further recruit more nanoparticles to accumulate at tumor sites after the PDT-induced damage of blood vessels through biochemotactic targeting, achieving continuous EGFR inhibition to prevent tumor proliferation and metastasis. In conclusion, this study not only provides a new strategy for the clinical treatment of breast cancer, but also provides a design idea for improving the targeted delivery of anti-tumor drugs.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Fotoquimioterapia/métodos , Porfirinas/farmacologia , Receptores ErbB , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124901, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39094268

RESUMO

Fluorescent solvatochromic dyes that are sensitive to the nature of local microenvironmental, have been explored as probes in applications ranging from the imaging biomolecules to understanding of basic biomolecule functions. To expand the scope of fluorescent solvatochromic dyes for G-quadruplex (G4) DNA structures, and to illustrate the relationship between structure and properties, three newly designed D-π-A type fluorescent dyes were synthesized by introducing diarylimidazole to carbazole skeleton linked to benzene, furan or thiophene π-conjugated bridge and connected with pyridinium acceptor, respectively. Their structural characteristics, optical properties, and G4 DNA binding properties were discussed in detail. In general, the incorporation of furan and thiophene as π-conjugated bridges leads the better conjugation and molecular coplanarity with more efficient intramolecular charge transfer (ICT) effect compared with benzene bridge. The fluorescence intensities induced upon interaction were found that TP-6 with thiophene π-conjugated bridge had the strongest response toward G4 DNAs. In addition, the application of this dye as a fluorescent agent for living cell imaging was also demonstrated.

15.
J Colloid Interface Sci ; 676: 506-520, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39047378

RESUMO

The synergistic anti-tumor impact of phototherapy and a cascading immune response are profoundly limited by hypoxia and a weakened immune response. Intravenous and intratumoral injection of therapeutic drugs also cause pain, rapid drug clearance and low utilization rates. Here, a novel cryo-millineedle platform for intratumoral delivery of a phototherapy system, S.epi@IR820, is developed in this work, combining the properties of Staphylococcus epidermidis (S. epidermidis) and IR820 for photo-immunotherapy of colorectal cancer. In this cryo-millineedle platform, S. epidermidis enhances the near-infrared absorption and light stability of IR820 and catalyzes the decomposition of H2O2 into O2 via an endogenous catalase to relieve tumor hypoxia, improve phototherapy and enhance immunogenic cell death (ICD). More interestingly, the native immunogenicity of S. epidermidis and ICD elicited by phototherapy achieved a potent anti-tumor immune response. To the best of our knowledge, this is the first study to utilize native S. epidermidis to relieve hypoxia and facilitate phototherapy. Both in vitro and in vivo experiments showed that the millineedle based phototherapy system can efficiently catalyse the decomposition of H2O2 into O2, facilitate phototherapeutic killing of CT26 tumor cells by S.epi@IR820 and enhance ICD, thus successfully activated the immune response and achieved the photo-immunotherapy against colorectal cancer. In conclusion, this study provides a novel strategy for enhanced anti-tumor efficiency of photo-immunotherapy, and develops an effective method for orthotopic administration of tumors.

16.
JACS Au ; 4(7): 2547-2556, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39055154

RESUMO

Biocatalysis is an effective approach for producing chiral drug intermediates that are often difficult to synthesize using traditional chemical methods. A time-efficient strategy is required to accelerate the directed evolution process to achieve the desired enzyme function. In this research, we evaluated machine learning-assisted directed evolution as a potential approach for enzyme engineering, using a moderately diastereoselective ketoreductase library as a model system. Machine learning-assisted directed evolution and traditional directed evolution methods were compared for reducing (±)-tetrabenazine to dihydrotetrabenazine via kinetic resolution facilitated by BsSDR10, a short-chain dehydrogenase/reductase from Bacillus subtilis. Both methods successfully identified variants with significantly improved diastereoselectivity for each isomer of dihydrotetrabenazine. Furthermore, the preparation of (2S,3S,11bS)-dihydrotetrabenazine has been successfully scaled up, with an isolated yield of 40.7% and a diastereoselectivity of 91.3%.

17.
Front Nutr ; 10: 1342100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38268669

RESUMO

Background: The relationship between sarcopenia and cirrhosis is unclear. In this research, our aim is to evaluate the prevalence of sarcopenia among individuals with liver cirrhosis and its correlation with survival and mortality risks. Methods: We conducted searches on PubMed, Web of Science, EMBASE, and Cochrane for English articles published up to July 10, 2023, and additionally manually searched the bibliography of relevant articles. We incorporated research on sarcopenia in patients with cirrhosis to examine the connection between sarcopenia and the likelihood of survival and mortality. Statistical analyses were carried out utilizing the Stata version 15.1 software. Depending on the heterogeneity of the results, we employed either fixed-effects models or random-effects models for data synthesis. To assess publication bias, we employed funnel plots and conducted Egger's test. Results: We included 40 studies involving 8,945 patients with cirrhosis. The overall prevalence of cirrhosis was 41% (95% CI 34%-48%). Male patients and those with liver cirrhosis and hepatic encephalopathy had a higher prevalence of sarcopenia (44% for male patients and 48% for hepatic encephalopathy patients). Sarcopenia emerged as a risk factor for both survival (HR = 2.57, 95% CI 2.02-3.27, p < 0.001) and mortality (HR = 2.13, 95% CI 1.86-2.44, p < 0.001) in patients with cirrhosis. Subgroup analyses consistently yielded the same results for study sites, whether HCC patients were excluded from the cohort, whether patients were from the liver transplant cohort or had undergone tips surgery, the definition of sarcopenia (L3-SMI or other methods), and the diagnostic criteria used by patients. The presence of sarcopenia was also a significant risk factor for hepatic encephalopathy [HR = 2.27, 95% CI (1.76-2.94), p < 0.001]. Conclusion: This systematic review and meta-analysis reveal that patients with cirrhosis have a prevalence of sarcopenia of 41% and is associated with survival rate and mortality rate. Therefore, we should attach importance to the screening of sarcopenia in patients with cirrhosis, early detection of susceptible populations, and appropriate measures to reduce the occurrence and adverse outcomes.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

18.
Adv Orthop ; 2023: 5306445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38155878

RESUMO

Objective: To investigate the safety and efficacy of piezosurgery in anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). Methods: 47 patients with complex CSM (cCSM) underwent ACDF surgery from 2014 to 2017. Among these patients, 26 underwent ACDF using piezosurgery (group A) and 21 underwent ACDF by using traditional tools such as high-speed air drill, bone curette, and Kerrison bone punch (group B). Average surgical time, intraoperative blood loss, surgical complications, preoperative and postoperative Japanese Orthopaedic Association (JOA) scores, and improvement rate were measured. Results: Average surgical time and intraoperative blood loss were significantly lower in group A than those in group B (P < 0.01). The incidences of surgical complications were 3.8% and 23.8% in the A and B groups (P < 0.05), respectively. There were no significant differences in JOA scores and improvement rates between data collection periods at preoperative, 3-day postoperative, and 1-year postoperative follow-ups (P > 0.05). Conclusion: For treating cCSM, both the piezosurgery and traditional tools led to significant neurological improvement. However, the piezosurgery was superior to the traditional tools in terms of surgical time, blood loss, and complication rate. Hence, piezosurgery was a safe and effective adjunct for ACDF treating cCSM.

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