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1.
Protein Sci ; 33(6): e5004, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723164

RESUMO

Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC50) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genética , Feminino , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Proliferação de Células/efeitos dos fármacos
2.
Nat Ecol Evol ; 8(5): 947-959, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38519631

RESUMO

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.


Assuntos
Culicidae , Mosquitos Vetores , Viroma , Animais , Culicidae/virologia , China , Mosquitos Vetores/virologia , Metagenômica , Arbovírus/genética , Arbovírus/classificação , Filogenia , Biodiversidade
3.
International Eye Science ; (12): 612-617, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012831

RESUMO

AIM:To compare the differences, correlations and consistency of IOL Master 700 or Lenstar LS900 in preoperative ocular biometry and the accuracy of intraocular lens(IOL)degree calculation of cataract patients with high myopia.METHODS: Retrospective study. A total of 136 cases(136 eyes)of high myopia and cataract patients who underwent phacoemulsification at the ophthalmology department of Army Medical Center of PLA from March 2021 to March 2023 were collected, with a mean age of 57.38±8.08 years. Patients were divided into 3 groups based on axial length(AL): 41 eyes in group A(26 mm≤ AL ≤28 mm), 43 eyes in group B(28 mm< AL ≤30 mm)and 52 eyes in group C(AL >30 mm). AL, mean keratometry(Km), anterior chamber depth(ACD), lens thickness(LT)and white-to-white(WTW)were preoperatively measured by two instruments, respectively. Barrett Universal II formula was used to calculate the IOL degrees of all patients, the appropriate reserved diopter was decided individually, and the prediction error(PE)and absolute error(AE)of the two instruments were compared.RESULTS:The AL and ACD of patients in the three groups measured by Lenstar LS900 were higher than the AL measurd by IOL Master 700(all P<0.05), with a difference of AL measured by the two devices: group C>group B>group A. However, there was no statistical significance in LT, Km, and WTW measured by the two instruments(all P>0.05). All biometric parameters measured by the two devices were positively correlated(all r>0.9, P<0.05), and consistent(95% LoA of all groups were narrow). There was no statistically significant difference in AE calculated by the two devices(P>0.05), but the IOL Master 700 calculated a smaller PE than Lenstar LS900(P<0.05), with lower percentage of hyperopic shift in IOL Master 700.CONCLUSION:In cataract patients with high myopia, AL measured by Lenstar LS900 is longer than that by IOL Master 700, and the differences of AL increase along with the growth of AL. Both devices have a good prediction for IOL calculation, but IOL Master 700 has less refractive error, lower percentage of hyperopic shift, and greater clinical advantages IOL Master 700.

4.
China Pharmacy ; (12): 578-583, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012576

RESUMO

OBJECTIVE To study the effects of the curcumin derivative bisdemethoxycurcumin (BC) promoting neuronal differentiation of neuroblastoma cells Neuro-2a (N2a) in mice and its mechanism. METHODS The effects of BC (1, 2, 4, 6, 8, 10 μmol/L) on the viability of N2a cells were detected by MTT assay to determine the concentration range of drug treatment. The control group, retinoic acid (RA) group (10 μmol/L) and BC groups (1, 2 and 4 μmol/L) were set up, and the length of neural protrusions of the differentiated cells was measured and the cell differentiation rate was calculated after 48 h and 72 h of culture. Compared with 0 min group, Western blot was used to detect the phosphorylation levels of protein kinase B (Akt), extracellular- signal regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38) proteins in cells treated by 4 μmol/L BC for 5, 15, 30, 60, 120 min. After intervention with inhibitors LY294002 (LY) and PD98059 (PD), the effects of BC on Akt and ERK1/2 protein phosphorylation levels and promoting neural differentiation were further validated. RESULTS According to the MTT experiment, the BC concentrations for subsequent induction of cell differentiation were determined to be 1, 2, and 4 μmol/L. After 48 hours of differentiation, compared with the control group, the cell differentiation rate in RA group and BC 1, 2 and 4 μmol/L groups, the length of cellular neural processes wjxhhxx413@163.com in the BC 4 μmol/L group significantly increased (P<0.05 or P<0.01);after inducing differentiation of BC for 72 hours,compared with the control group, the cell differentiation rate and the length of cellular neural processes in the RA group, the cell differentiation rate in the BC 4 μmol/L group, and the length of cellular neural processes in the BC 2 μmol/L group all significantly increased (P<0.05 or P<0.01).Compared with the 0 min group, the phosphorylation levels of Akt, ERK1/2, and p38 proteins in cells of the 5, 15, 30, 60 and 120 min groups increased to varying degrees after treated by 4 μmol/L BC, and some differences were statistically significant (P<0.05 or P<0.01). After adding the inhibitor LY/PD, compared with the BC group, the phosphorylation level of ERK1/2 protein in the PD+BC group cells were significantly reduced (P<0.01), and the cell differentiation rates in the LY group, LY+BC group, PD group, and PD+BC group was significantly reduced (P<0.01). CONCLUSIONS BC promotes N2a cell differentiation mainly by increasing cell differentiation rate and neural protrusion length. The mechanism may be related to the activation of mitogen-activated protein kinase/ ERK and PI3K/Akt signaling pathways.

5.
Birth Defects Res ; 116(1): e2277, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38158794

RESUMO

PURPOSE: The purpose of this study is to explore the regulatory function of COL1A1 against the apoptosis of embryonic stem cells (ESCs) and the potential function in congenital talipes equinovarus (CTEV). METHODS: Muscle tissues were collected from 20 children with CTEV and 20 children without CTEV, followed by detecting the expression of COL1A1 using the RT-PCR method. COL1A1 was knocked down in H1 and H9 human ESCs using the RNA interference technology, followed by determining the level of COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax using the Western blotting assay. RESULTS: COL1A1 was found markedly upregulated in muscle tissues of CTEV children. In H1 and H9 human ESCs, compared to the empty vector, COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax were found notably downregulated after transfected with the siRNA targeting COL1A1. CONCLUSION: COL1A1 induced the apoptosis of ESCs by mediating the PITX1/TBX4 signaling and might be a potential target for treating CTEV.


Assuntos
Pé Torto Equinovaro , Criança , Humanos , Apoptose/genética , Proteína X Associada a bcl-2/genética , Pé Torto Equinovaro/genética , Células-Tronco Embrionárias , Proteínas com Domínio T/genética
6.
Sci Rep ; 13(1): 19239, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935818

RESUMO

Aiming at the problems of backward calibration method of smoke alarm, low production efficiency and difficult real-time monitoring, a digital twin system modeling and monitoring method of smoke alarm calibration is proposed. First, through the analysis of smoke alarm calibration requirements, the overall framework design of the digital twin calibration system for smoke alarm is proposed, and then the twin model of smoke box is constructed by running the digital twin five-dimensional model. The physical smoke box, geometric model, physical model, rule model and behavior model are introduced in detail; Then the communication system architecture, data acquisition and data mapping are used to construct the twin data model; Finally, the feasibility was verified by the calibration system of an enterprise. Through the system, the qualified rate of smoke alarm calibration was increased from 98 to 99.6%, and the repair rate of defective products was reduced by 1.6%.

7.
RSC Adv ; 13(45): 31595-31601, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37908644

RESUMO

The K2S2O8-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC50 values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.

8.
J Infect Dis ; 228(Suppl 3): S180-S188, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37703347

RESUMO

The estimated prevalence of anti-HCV was 3.1% in Taiwan. Studies have shown iatrogenic behavior was the major transmission route. It is highest in specific populations including patients with end stage renal disease (ESRD), human immunodeficiency virus infection, who inject drug (PWID), and under opioid substitution treatment. Approximately 405,160 patients were seropositive for HCV RNA and in need of treatment. Taiwan government claims to reach WHO's 2030 goal of HCV elimination by 2025 and works hard to resolve several barriers of HCV elimination including political commitment, sustainable financing, minimize reimbursement restrictions, instituted monitoring, and perform micro-elimination of specific populations. The last stage of HCV elimination is to accelerate the universal HCV screening program of populations aged 45-79 years and resolve the unawareness issue of HCV infection. Hopefully, we can achieve the targets of HCV elimination set by WHO and reach the goal earlier in 2025.


Assuntos
Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Taiwan/epidemiologia , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Políticas , Governo
9.
bioRxiv ; 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37732272

RESUMO

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

10.
Materials (Basel) ; 16(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37049154

RESUMO

TC31 is a new type of high-temperature titanium alloy, but few researchers have studied the combination of forming and heat treatment of a component using this material. The component with high ribs and thin webs was studied by numerical simulation and trail production. Based on the establishment of the finite element model, the forming process was analyzed by simulation software, and the maximum forming load of the component was 1920 kN. Ultimately, there were no folding defects of the component during the forming process. The material flow law was revealed by selecting the typical section of the component, and then the forming process was verified and the fully filled component was obtained. After that, the component was subjected to post-processing, and three heat treatment methods were designed to conduct heat treatment experiments on it (heat treatment: solution treatment and aging treatment). By analyzing the influence of three heat treatment methods on mechanical properties, the optimal heat treatment method was obtained, namely a solution treatment at 960 °C for 2.5 h and aging treatment at 610 °C for 7 h. The ultimate tensile strength, yield strength, elongation, and section shrinkage of the component through forging forming and heat treatment are higher than those of original material; meanwhile, it also indicates that the designed heat treatment has a better effect on the high-temperature mechanical properties of this titanium alloy at 650 °C than that at 450 °C. The research on the combination of the forming and heat treatment of this component provides a reference for the engineering application of high-temperature titanium alloys.

11.
J Enzyme Inhib Med Chem ; 38(1): 2166039, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36683274

RESUMO

Inhibiting a specific target in cancer cells and reducing unwanted side effects has become a promising strategy in pancreatic cancer treatment. MAP4K4 is associated with pancreatic cancer development and correlates with poor clinical outcomes. By phosphorylating MKK4, proteins associated with cell apoptosis and survival are translated. Therefore, inhibiting MAP4K4 activity in pancreatic tumours is a new therapeutic strategy. Herein, we performed a structure-based virtual screening to identify MAP4K4 inhibitors and discovered the compound F389-0746 with a potent inhibition (IC50 120.7 nM). The results of kinase profiling revealed that F389-0746 was highly selective to MAP4K4 and less likely to cause side effects. Results of in vitro experiments showed that F389-0746 significantly suppressed cancer cell growth and viability. Results of in vivo experiments showed that F389-0746 displayed comparable tumour growth inhibition with the group treated with gemcitabine. These findings suggest that F389-0746 has promising potential to be further developed as a novel pancreatic cancer treatment.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Humanos , Linhagem Celular Tumoral , Gencitabina/química , Gencitabina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Pancreáticas/enzimologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Simulação por Computador , Neoplasias Pancreáticas
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009014

RESUMO

OBJECTIVE@#To investigate the effect of ultrasonic bone curette in anterior cervical spine surgery.@*METHODS@#A clinical data of 63 patients with cervical spondylosis who were admitted between September 2019 and June 2021 and met the selection criteria was retrospectively analyzed. Among them, 32 cases were operated with conventional instruments (group A) and 31 cases with ultrasonic bone curette (group B). There was no significant difference between the two groups (P>0.05) in gender, age, surgical procedure, surgical segment and number of occupied cervical space, disease type and duration, comorbidities, and preoperative Japanese Orthopaedic Association (JOA) score, cervical dysfunction index (NDI), and pain visual analogue scale (VAS) score. The operation time, intraoperative bleeding, postoperative drainage, postoperative hospital stay, and the occurrence of postoperative complications were recorded in both groups. Before operation and at 1, 3, and 6 months after operation, the JOA score and NDI were used to evaluate the function and the postoperative JOA improvement rate was calculated, and VAS score was used to evaluate the pain improvement. The anteroposterior and lateral cervical X-ray films were taken at 1, 3, and 6 months after operation to observe whether there was any significant loosening and displacement of internal fixators.@*RESULTS@#Compared with group A, group B had shorter operation time and postoperative hospital stay, less intraoperative bleeding and postoperative drainage, and the differences were significant (P<0.05). All incisions healed by first intention in the two groups, and postoperative complications occurred in 5 cases (15.6%) in group A and 2 cases (6.5%) in group B, showing no significant difference (P>0.05). All patients were followed up 6-12 months (mean, 7.9 months). The JOA score and improvement rate gradually increased in groups A and B after operation, while the VAS score and NDI gradually decreased. There was no significant difference in VAS score between 3 months and 1 month in group B (P>0.05), and there were significant differences between the other time points of each indicator in the two groups (P<0.05). At 1, 3, and 6 months after operation, the JOA score and improvement rate in group B were better than those in group A (P<0.05). X-ray films examination showed that there was no screw loosening or titanium plate displacement in the two groups after operation, and the intervertebral cage or titanium mesh significantly sank.@*CONCLUSION@#Compared with traditional instruments, the use of ultrasonic bone curette assisted osteotomy in anterior cervical spine surgery has the advantages of shorter operation time, less intraoperative bleeding, less postoperative drainage, and shorter hospital stay.


Assuntos
Humanos , Ultrassom , Estudos Retrospectivos , Titânio , Complicações Pós-Operatórias/epidemiologia , Placas Ósseas , Vértebras Cervicais/cirurgia
13.
Organ Transplantation ; (6): 106-2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-959027

RESUMO

Objective To analyze clinical prognosis, risk factors and predictive indexes of hyperkalemia in recipients after heart transplantation. Methods Clinical data of 158 recipients were retrospectively analyzed. According to the serum potassium levels within postoperative 1-year follow-up, all recipients were divided into the normal serum potassium level group (n=83), hyperkalemia group (n=43) and severe hyperkalemia group (n=32). The incidence and prognosis of hyperkalemia after heart transplantation were summarized. The risk factors and predictive indexes of hyperkalemia after heart transplantation were identified. Results The incidence of hyperkalemia and severe hyperkalemia within postoperative 1 year was 47.5%(75/158) and 20.3%(32/158), respectively. In the severe hyperkalemia group, the fatality was 16%(5/32), higher than 8%(7/83) in the normal serum potassium level group and 7%(3/43) in the hyperkalemia group. The mean serum creatinine (Scr) within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d were the independent risk factors for hyperkalemia following heart transplantation (all P < 0.05). The mean Scr level within 6 months before heart transplantation, postoperative hemodialysis time, and Scr levels at postoperative 1 and 7 d could be used to predict postoperative severe hyperkalemia. Conclusions The recipients with severe hyperkalemia after heart transplantation obtain poor prognosis. The mean Scr level within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, and the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d are the independent risk factors for hyperkalemia after heart transplantation. Perioperative Scr level and postoperative hemodialysis time may be used to predict the incidence of severe hyperkalemia within 1 year after heart transplantation.

14.
Organ Transplantation ; (6): 56-2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-959020

RESUMO

Pediatric heart transplantation is the standard treatment for children complicated with refractory heart failure which is difficult to be treated by conventional surgery or drugs. At present, an increasing quantity of pediatric heart transplantation is being performed worldwide, whereas relevant experience is still lacking in China. In recent 10 years, significant progress has been achieved in pediatric heart transplantation. On one hand, the number of pediatric heart transplantation has been increased year by year. On the other hand, ABO-incompatible heart transplantation, application of ventricular assist device in children, and recipient-donor weight mismatch transplantation have been widely employed to resolve the shortage of donor heart in pediatric heart transplantation. However, relevant experience of pediatric heart transplantation is lacking in China, especially in understanding the indications of pediatric heart transplantation and the application of specific strategies for pediatric heart transplantation, etc. In this article, the development history, advances in therapeutic strategy and clinical prognosis of pediatric heart transplantation were reviewed.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015651

RESUMO

Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1014631

RESUMO

AIM: To explore the improvement effect and mechanism of crocin on cognitive impairmrnt of Alzheimer's disease (AD) rats. METHODS: The hippocampus of SD rats were injected with Aβ 25-35 to establish AD model, then rats were randomly divided into AD group, AD + low, medium, high dose of crocin groups (10, 20, 40 mg/kg) and AD + donepezil group (1 mg/kg), intraperitoneal injection treatment for 4 weeks, set sham group. Dark avoidance test and water maze test were used to evaluate the learning and memory abilities of rats, ELISA was used to detect serum Aβ content, HE staining and Tunel staining were used to determine pathological changes and neuronal apoptosis of hippocampus of rats, immunohistochemistry was used to detect the expression of Brdu, Dcx and NeuN in hippocampus of rats, and Western blot was used to detect the protein expression of Aβ, DKK3, β-catenin, p-GSK-3β/GSK-3β, Caspase-3, Bax, Bcl-2 in hippocampus of rats. RESULTS: Compared to sham group, the learning and memory abilities of AD group rats were decreased, serum Aβ content increased, the pathological change in hippocampus was serious, neuronal apoptosis was increased, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/GSK-3β, Caspase-3, Bax were increased, protein expression of β-catenin, Bcl-2 were decreased (P<0.01). Compared to AD group, after the treatment of doses of crocin and donepezil, the learning and memory abilities of AD rats were improved, serum Aβ content were increased, and the pathological change in hippocampus were alleviated, neuronal apoptosis were reduced, the expression of Brdu, Dcx, NeuN were decreased, the protein expression of Aβ, DKK3, p-GSK-3β/ GSK-3β, Caspase-3, Bax were decreased, the protein expression of β-catenin, Bcl-2 were increased, notely, dose-dependent effect of crocin was significant. CONCLUSION: Crocin reduced neuronal apoptosis and mediated DKK3 to regulate GSK-3β/ β-catenin pathway to improve the cognitive impairment of AD rats.

17.
Chinese Pharmacological Bulletin ; (12): 1478-1484, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013742

RESUMO

Aim To investigate the effect of dapagliflozin on the small conductance calcium-activated potassium channel 2 (SK2 channel) protein in the myocardium of diabetic rats and its possible mechanism of action. Methods In vivo: type 2 diabetes model was established by high-glucose and high-fat diet combined with intraperitoneal injection of low-dose streptozotocin (35 mg

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981610

RESUMO

OBJECTIVE@#To investigate the surgical technique and effectiveness of titanium elastic nail (TEN) assisted retrograde channel screw implantation of superior pubic branch.@*METHODS@#The clinical data of 31 patients with pelvic or acetabular fractures treated with retrograde channel screw implantation in superior pubic branch between January 2021 and April 2022 were retrospectively analyzed. Among them, 16 cases were implanted with assistance of TEN (study group) and 15 cases were implanted under the guidance of C-arm X-ray machine (control group). There was no significant difference in gender, age, cause of injury, Tile classification of pelvic fracture, Judet-Letournal classification of acetabular fracture, and time from injury to operation between the two groups ( P>0.05). The operation time, fluoroscopy times, and intraoperative blood loss of each superior pubic branch retrograde channel screw were recorded during operation. X-ray films and three-dimensional CT were reexamined after operation, the quality of fracture reduction was evaluated by Matta score standard, and the position of channel screw was evaluated by screw position classification standard. The fracture healing time was recorded during the follow-up, and the postoperative functional recovery was evaluated by Merle D'Aubigne Postel score system at last follow-up.@*RESULTS@#Nineteen and 20 retrograde channel screws of superior pubic branch were implanted in the study group and the control group, respectively. The operation time, fluoroscopy times, and intraoperative blood loss of each screw in the study group were significantly less than those in the control group ( P<0.05). According to the postoperative X-ray films and three-dimensional CT, none of the 19 screws in the study group penetrated out of the cortical bone or into the joint, and the excellent and good rate was 100% (19/19); in the control group, there were 4 screws of cortical bone penetration, and the excellent and good rate was 80% (16/20); the difference between the two groups was significant ( P<0.05). Matta score standard was used to evaluate the quality of fracture reduction, there was no patient in the two groups with poor reduction results, and the difference was not significant between the two groups ( P>0.05). The incisions of the two groups healed by first intention, and there was no complication such as incision infection, skin margin necrosis, and deep infection. All patients were followed up 8-22 months, with an average of 14.7 months. There was no significant difference in healing time between the two groups ( P>0.05). At last follow-up, the difference in functional recovery evaluated by the Merle D'Aubigne Postel scoring system between the two groups was not significant ( P>0.05).@*CONCLUSION@#TEN assisted implantation technique can significantly shorten the operation time of retrograde channel screw implantation of superior pubic branch, reduce the times of fluoroscopy, and have less intraoperative blood loss and accurate screw implantation, which provides a new safe and reliable method for minimally invasive treatment of pelvic and acetabular fractures.


Assuntos
Humanos , Titânio , Fixação Interna de Fraturas/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Parafusos Ósseos , Resultado do Tratamento , Fraturas Ósseas/cirurgia , Fraturas da Coluna Vertebral , Fraturas do Quadril
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981316

RESUMO

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.


Assuntos
Arsênio/análise , Arsenicais/análise , Sulfetos , Trióxido de Arsênio , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/análise , Produtos Biológicos
20.
Asian Journal of Andrology ; (6): 339-344, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-981949

RESUMO

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.


Assuntos
Masculino , Humanos , Análise do Sêmen , Sêmen , Motilidade dos Espermatozoides , Contagem de Espermatozoides , Astenozoospermia , Espermatozoides
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