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1.
Eur J Med Res ; 29(1): 322, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858682

ABSTRACT

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.


Subject(s)
Autism Spectrum Disorder , Humans , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/therapy , Quality of Life , Precision Medicine/methods
2.
Article in English | MEDLINE | ID: mdl-38775884

ABSTRACT

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.

3.
Medicine (Baltimore) ; 103(21): e38260, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788026

ABSTRACT

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.


Subject(s)
Biomarkers , Computational Biology , Pre-Eclampsia , Humans , Female , Pre-Eclampsia/blood , Pre-Eclampsia/immunology , Pre-Eclampsia/diagnosis , Pre-Eclampsia/genetics , Pregnancy , Computational Biology/methods , Biomarkers/blood , ROC Curve , Adult , Gene Expression Profiling/methods
4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 529-534, 2024 May 15.
Article in Chinese | MEDLINE | ID: mdl-38752237

ABSTRACT

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.


Subject(s)
Cervical Vertebrae , Decompression, Surgical , Printing, Three-Dimensional , Spinal Fusion , Spondylosis , Humans , Spondylosis/surgery , Cervical Vertebrae/surgery , Retrospective Studies , Spinal Fusion/methods , Spinal Fusion/instrumentation , Male , Decompression, Surgical/methods , Female , Treatment Outcome , Bone Plates , Vertebral Body/surgery , Spinal Cord Diseases/surgery , Middle Aged
5.
J Agric Food Chem ; 72(17): 9567-9580, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38627202

ABSTRACT

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.


Subject(s)
Cheese , Citrinin , Food Contamination , Monascus , Monascus/metabolism , Monascus/chemistry , Cheese/microbiology , Cheese/analysis , Citrinin/analysis , Food Contamination/analysis , Food Contamination/prevention & control , Humans , Fermentation
6.
Biomed Pharmacother ; 175: 116627, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38653112

ABSTRACT

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.


Subject(s)
Nanoparticles , Protein Corona , Protein Corona/metabolism , Protein Corona/chemistry , Humans , Animals , Drug Delivery Systems/methods , Protein Engineering/methods , Surface Properties
7.
Neurol Sci ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38653915

ABSTRACT

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.

8.
Zhongguo Gu Shang ; 37(2): 153-8, 2024 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-38425066

ABSTRACT

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.


Subject(s)
Anterior Cruciate Ligament Injuries , Knee Injuries , Posterior Cruciate Ligament , Soft Tissue Injuries , Humans , Adult , Middle Aged , Magnetic Resonance Imaging/methods , Arthroscopy , Knee Injuries/diagnostic imaging , Knee Joint/diagnostic imaging , Posterior Cruciate Ligament/injuries , Tomography, Spiral Computed , Anterior Cruciate Ligament Injuries/diagnostic imaging
9.
Arch Gynecol Obstet ; 310(1): 103-111, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38342828

ABSTRACT

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.


Subject(s)
Cesarean Section , Cicatrix , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Signal Transduction , Umbilical Cord , Wound Healing , Animals , Female , Mesenchymal Stem Cell Transplantation/methods , Rats , Pregnancy , Umbilical Cord/cytology , Humans , Cicatrix/metabolism , Rats, Sprague-Dawley , Uterus/metabolism , Transforming Growth Factor beta/metabolism , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism , Smad3 Protein/metabolism , Smad2 Protein/metabolism
10.
Pak J Med Sci ; 40(3Part-II): 326-331, 2024.
Article in English | MEDLINE | ID: mdl-38356823

ABSTRACT

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.

11.
Eur J Pharmacol ; 966: 176348, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38286356

ABSTRACT

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.


Subject(s)
Emodin , Rheum , Rats , Animals , Rats, Sprague-Dawley , Liposomes , Anthraquinones/pharmacology , Anthraquinones/therapeutic use , Lipids
12.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2437-2445, 2024 04.
Article in English | MEDLINE | ID: mdl-37847411

ABSTRACT

Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking ß-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/ß-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , beta Catenin/metabolism , Wnt Signaling Pathway , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic
13.
Biomater Sci ; 12(3): 691-709, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38099460

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Nanoparticles , Photochemotherapy , Porphyrins , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Photochemotherapy/methods , Porphyrins/pharmacology , ErbB Receptors , Photosensitizing Agents/pharmacology , Cell Line, Tumor
14.
Adv Orthop ; 2023: 5306445, 2023.
Article in English | MEDLINE | ID: mdl-38155878

ABSTRACT

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.

15.
Front Pharmacol ; 14: 1243613, 2023.
Article in English | MEDLINE | ID: mdl-37954849

ABSTRACT

The tumor microenvironment affects the structure and metabolic function of mitochondria in tumor cells. This process involves changes in metabolic activity, an increase in the amount of reactive oxygen species (ROS) in tumor cells compared to normal cells, the production of more intracellular free radicals, and the activation of oxidative pathways. From a practical perspective, it is advantageous to develop drugs that target mitochondria for the treatment of malignant tumors. Such drugs can enhance the selectivity of treatments for specific cell groups, minimize toxic effects on normal tissues, and improve combinational treatments. Mitochondrial targeting agents typically rely on small molecule medications (such as synthetic small molecules agents, active ingredients of plants, mitochondrial inhibitors or autophagy inhibitors, and others), modified mitochondrial delivery system agents (such as lipophilic cation modification or combining other molecules to form targeted mitochondrial agents), and a few mitochondrial complex inhibitors. This article will review these compounds in three main areas: oxidative phosphorylation (OXPHOS), changes in ROS levels, and endogenous oxidative and apoptotic processes.

16.
Front Neurol ; 14: 1153563, 2023.
Article in English | MEDLINE | ID: mdl-37396772

ABSTRACT

Objectives: The network mechanism underlying the initial response to antiseizure medication in epilepsy has not been revealed yet. Given the central role of the thalamus in the brain network, we conducted a case-control study to investigate the association between thalamic connectivity and medication response. Methods: We recruited 39 patients with newly diagnosed and medication-naïve epilepsy of genetic or unknown etiology, including 26 with a good response (GR group) and 13 with a poor response (PR group), and 26 matched healthy participants (control group). We measured the gray matter density (GMD) and the amplitude of low-frequency fluctuation (ALFF) of bilateral thalami. We then set each thalamus as the seed region of interest (ROI) to calculate voxel-wise functional connectivity (FC) and assessed ROI-wise effective connectivity (EC) between the thalamus and targeted regions. Results: We found no significant difference between groups in the GMD or ALFF of bilateral thalami. However, we observed that the FC values of several circuits connecting the left thalamus and the cortical areas, including the bilateral Rolandic operculum, the left insula, the left postcentral gyrus, the left supramarginal gyrus, and the left superior temporal gyrus, differed among groups (False Discovery Rate correction, P < 0.05), with a higher value in the PR group than in the GR group and/or the control group (Bonferroni correction, P < 0.05). Similarly, both the outflow and the inflow EC in each thalamocortical circuit were higher in the PR group than in the GR group and the control group, although these differences did not remain statistically significant after applying the Bonferroni correction (P < 0.05). The FC showed a positive correlation with the corresponding outflow and inflow ECs for each circuit. Conclusion: Our finding suggested that patients with stronger thalamocortical connectivity, potentially driven by both thalamic outflowing and inflowing information, may be more likely to respond poorly to initial antiseizure medication.

17.
Aquac Nutr ; 2023: 9155290, 2023.
Article in English | MEDLINE | ID: mdl-37520289

ABSTRACT

The optimum phenylalanine (Phe) requirement for hybrid grouper (Epinephelusfuscoguttatus ♀ × Epinepheluslanceolatus ♂) juveniles was determined through an 8-week growth trial. A total of seven isoenergetic (340 kcal per 100 g of dry matter), isonitrogenous, and isolipidic diets were made, containing 8.2 (Phe 8.2), 9.2 (Phe 9.2), 10.1 (Phe 10.1), 11.2 (Phe 11.2), 13.3 (Phe 13.3), 15.2 (Phe 15.2), and 17.3 g/kg (Phe 17.3), respectively. Triplicate tanks of juvenile fish (about 16.7 g/fish) were fed each experimental diet twice daily until apparent satiation. The results indicated that different dietary Phe levels significantly influenced weight gain percentage (WG), feed efficiency (FE), protein efficiency ratio (PER), as well as, productive protein value (PPV). Fish fed Phe 8.2 had the lowest WG or PPV among all experimental treatments. Furthermore, the optimal dietary Phe level increased fold height, width, enterocyte, and microvillus height of fish. The Phe 10.1 group exhibited higher growth hormone (GH) expression in the pituitary compared to other groups. Expression of hepatic insulin-like growth factor-1 (IGF-1) and growth hormone receptor 1 (GHR1) displayed a similar pattern of variation to that of GH. The Phe 13.3 group had lower expression of S6 kinase 1 (S6K1) and target of rapamycin (TOR) than other groups. In addition, fish fed Phe 10.1 had lower levels of nuclear factor erythroid 2 (Nrf2) and heat shock protein 70 (HSP70) in the head kidney, and Cu/Zn-superoxide (Cu/ZnSOD) dismutases in the midgut compared to fish fed other Phe levels. Generally, optimal Phe content in the diet of hybrid grouper was estimated to be 12.7 g/kg of dry matter (27.3 g/kg of dietary protein), and at this level, the feed utilization, gut micromorphology, and immunity of fish were also elevated.

18.
Front Plant Sci ; 14: 1142211, 2023.
Article in English | MEDLINE | ID: mdl-37384362

ABSTRACT

Rusty root syndrome is a common and serious disease in the process of Panax ginseng cultivation. This disease greatly decreases the production and quality of P. ginseng and causes a severe threat to the healthy development of the ginseng industry. However, its pathogenic mechanism remains unclear. In this study, Illumina high-throughput sequencing (RNA-seq) technology was used for comparative transcriptome analysis of healthy and rusty root-affected ginseng. The roots of rusty ginseng showed 672 upregulated genes and 526 downregulated genes compared with the healthy ginseng roots. There were significant differences in the expression of genes involved in the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction. Further analysis showed that the cell wall synthesis and modification of ginseng has a strong response to rusty root syndrome. Furthermore, the rusty ginseng increased aluminum tolerance by inhibiting Al entering cells through external chelating Al and cell wall-binding Al. The present study establishes a molecular model of the ginseng response to rusty roots. Our findings provide new insights into the occurrence of rusty root syndrome, which will reveal the underlying molecular mechanisms of ginseng response to this disease.

19.
Ecotoxicology ; 32(6): 711-719, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37386302

ABSTRACT

As luminescent nanomaterials, the carbon quantum dots (CQDs) research focused on emerging applications since their discovery. However, their toxicological effects on the natural environment are still unclear. The freshwater planarian Dugesia japonica is distributed extensively in aquatic ecosystems and can regenerate a new brain in 5 days after amputation. Therefore it can be used as a new model organism in the field of neuroregeneration toxicology. In our study, D. japonica was cut and incubated in medium treated with CQDs. The results showed that the injured planarian lost the neuronal ability of brain regeneration after treatment with CQDs. Its Hh signalling system was interfered with at Day 5, and all cultured pieces died on or before Day 10 due to head lysis. Our work reveals that CQDs might affect the nerve regeneration of freshwater planarians via the Hh signalling pathway. The results of this study improve our understanding of CQD neuronal development toxicology and can aid in the development of warning systems for aquatic ecosystem damage.


Subject(s)
Planarians , Quantum Dots , Animals , Planarians/physiology , Ecosystem , Quantum Dots/toxicity , Brain
20.
PeerJ ; 11: e15481, 2023.
Article in English | MEDLINE | ID: mdl-37273534

ABSTRACT

Objectives: To investigate the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1) in the mucosal tissues and peripheral blood of patients with ulcerative colitis (UC). Methods: Eighty patients with UC were recruited from January 2021 to August 2022 from the Shanxi Province People's Hospital. PD-1 and PD-L1 expression was assessed by immunohistochemistry in mucosal tissues. An enzyme-linked immunosorbent assay was used to measure soluble PD-1 and PD-L1 levels in peripheral blood serum, and the membrane-bound forms of PD-1 (mPD-1), (T-helper cell) Th1 and Th17, in peripheral blood were determined by flow cytometry. Result: PD-1 expression was observed only in the monocytes of the mucosal lamina propria of UC patients, while PD-L1 was mainly located in both epithelial cells and monocytes on the cell membrane. The expression level of PD-1/PD-L1 in the monocytes and epithelial cells of mucosal lamina propria increased with disease activity (P < 0.05). The percentages of PD-1/T and PD-1/CD4+T in the peripheral blood of moderate UC patients (PD-1/T 12.83 ± 6.15% and PD-1/CD4+T 19.67 ± 9.95%) and severe UC patients (PD-1/T 14.29 ± 5.71% and PD-1/CD4+T 21.63 ± 11.44%) were higher than in mild UC patients (PD-1/T 8.17 ± 2.80% and PD-1/CD4+T 12.44 ± 4.73%; P < 0.05). There were no significant differences in PD-1/CD8+T cells between mild and severe UC patients (P > 0.05). There was a statistically significant difference in the expression level of sPD-L1 between the UC groups and healthy controls, and the expression level of sPD-L1 increased with disease severity (P < 0.05); however, there was no statistically significant difference in sPD-1 expression levels between the UC groups and healthy controls (P > 0.05). The correlation coefficients between Th1 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.427, 0.589, 0.486, and 0.329, respectively (P < 0.001). The correlation coefficients between Th17 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.323, 0.452, 0.320, and 0.250, respectively (P < 0.05). Conclusion: The expression level of PD-1/PD-L1 was correlated with UC disease activity, and two forms of PD-1 and PD-L1 may be used as a potential marker for predicting UC and assessing disease progression in UC patients. PD-1/PD-L1 imbalance was a significant phenomenon of UC immune dysfunction. Future research should focus on two forms of PD-1/PD-L1 signaling molecules to better understand the pathogenesis of UC and to identify potential drug therapies.


Subject(s)
Colitis, Ulcerative , Humans , B7-H1 Antigen , Programmed Cell Death 1 Receptor , Ligands , Enzyme-Linked Immunosorbent Assay
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