Risk assessment tool for anemia of chronic disease in systemic lupus erythematosus: a prediction model.

OBJECTIVE: This study aims to develop a predictive model for estimating the likelihood of anemia of chronic disease (ACD) in patients with systemic lupus erythematosus (SLE) and to elucidate the relationship between various factors and ACD METHODS: Individuals diagnosed with SLE for at least one year were enrolled and categorized into two groups: those with ACD and those without anemia symptoms. Patients were randomly assigned to training and test sets at an 8:2 ratio. The least absolute shrinkage and selection operator (LASSO) method was used to select predictors, followed by logistic regression for modeling. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) for both training and test sets. RESULTS: The study included a total of 216 patients, with 172 in the training set and 44 in the test set. LASSO identified 6 variables for constructing the predictive model, resulting in an area under the curve (AUC) of 0.833 (95% CI, 0.773-0.892) in the training set and 0.861 (95% CI, 0.750-0.972) in the test set. Calibration curves indicated consistency between expected and observed probabilities. DCA indicated that the model yielded a net benefit with threshold probabilities ranging from 20% to 90% in the training set and from 10% to 80% in the test set. CONCLUSION: This study presents a predictive model for assessing the risk of ACD in SLE patients. The model effectively captures the underlying mechanism of ACD in SLE and empowers clinicians to make well-informed treatment adjustments. Key Points • Development of a New Predictive Model: This study introduces a new predictive model to evaluate the likelihood of anemia of chronic disease (ACD) in patients with systemic lupus erythematosus (SLE). The model utilizes routine laboratory parameters to identify high-risk individuals, addressing a significant gap in current clinical practice. • Reflection of Potential Mechanisms for ACD Development: By incorporating the factors needed to construct the predictive model, this study also sheds light on the potential mechanisms of ACD development in SLE patients.

Attitudes toward an HPV vaccine for condyloma acuminata and willingness to undergo vaccination among STD clinic attendees in China: Focus on STI prevention with HPV vaccine.

BACKGROUND: Condyloma acuminata (CA) is a common, and recurrent sexually transmitted disease (STD) that greatly contributes to direct health care costs and has a substantial psychosocial impact. Human papillomavirus (HPV) vaccination (containing L1 protein for HPV types 6 and 11) effectively controls CA. OBJECTIVES: We investigated attitudes toward the HPV vaccine for CA and willingness to undergo vaccination among STD clinic attendees in China. METHODS: Attendees at STD clinics at two selected hospitals in Guangdong and Jiangsu Provinces from May to September 2017 were requested to complete a self-administered questionnaire for this cross-sectional study. RESULTS: The participants' median age was 28 years (IQR: 24.0-34.0), and the sex ratio was balanced; 63.5% were from Guangdong, 36.5% were from Jiangsu, and 44.5% had a history of CA. The vaccine acceptance rate was high among the participants (85.8%,235/274) to whom the HPV vaccine for CA was available, especially among those who had heard of CA (89.0%, AOR = 3.14, 95% CI: 1.29-7.63, p = 0.0114). 95 (34.7%) of 274 participants had a positive attitude toward the HPV vaccine for CA. STD clinic attendees who had heard of the connection between HPV and CA (AOR = 2.56, 95% CI: 1.31-5.00, p = 0.0060), had heard of the HPV vaccines or cervical cancer vaccines (AOR = 1.90, 95% CI: 1.02-3.54, p = 0.0444) and had ever proactively discussed CA or the vaccine with others (AOR = 1.95, 95% CI:1.00-3.79, p = 0.0488) had better attitudes toward the HPV vaccine for CA. Over half of the participants (52.5%) expected the price of the HPV vaccine for CA to be under $90. CONCLUSION: The acceptance of the HPV vaccine for CA was high among STD clinic attendees in China, and the participants' self-perceived knowledge of CA and HPV was associated with better attitudes toward the HPV vaccine for CA. Education to improve knowledge is vital for reducing vaccine hesitancy.

Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration.

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.

Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica / 解剖学报

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Transcriptome Profiling of Male Adult Angiostrongylus cantonensis.

Background: The pathogen of angiostrongyliasis is the parasite Angiostrongylus cantonensis, and the transcriptome profiling of the male adult was unclear. We aimed to understand how the male adults adapt, so the expression profile of A. cantonensis adult males was analyzed. Methods: In order to improve the understanding of the transcriptome of adult males, RNA from three groups of male adult A. cantonensis was extracted and reverse transcribed to construct cDNA libraries. After sequencing, annotation of unigenes and transcripts was performed by querying the NR (Non-Redundant Protein Sequence Database), GO (Gene Ontology) and COG/KOG (Clusters of Orthologous Groups of proteins/euKaryotic Ortholog Groups) databases. Results: For each group of adults, 43,260,894 raw reads and 43,200,341 clean reads were obtained. After successful assembly, 87,649 unigenes and 146,895 transcripts were obtained. Annotation of the unigenes and transcripts was identical and male adults expressed a series of genes encoding proteins specific to the male gender at the adult stage, such as proteins involved in energy metabolism, energy synthesis and transport. Expression of the ribosome pathway suggests a relationship with the physical activities during the adult male stage. Conclusion: The transcriptome analysis is a good reference to understand further the expression profile of male adult A. cantonensis.

IgE antibody responses in cerebrospinal fluids relate to the brain pathologic injury of hosts with Angiostrongylus cantonensis infection.

BACKGROUND: The immunoglobulin E (IgE) response to Angiostrongylus cantonensis infection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice. METHODS: BALB/c (high susceptibility), CBA (medium), and C57BL/6 and C57BL/10 (resistance) strain mice were used in this study. The levels of IgM, IgG, and IgE in the serum and cerebrospinal fluid (CSF) from infected mice were compared. A. cantonensis-reactive antigens from BALB/c and C57BL/6 mice CSF were also analyzed. RESULTS: Antibodies against fifth-stage larvae (L5) antigens increased in mice CSF, particularly IgE, relate to worm rejection and the susceptibility of different mouse strains. The increased IgE level in BALB/c mice CSF is lower than that from others, suggesting IgE response in brain is more important than that in serum. Anti-L5 and anti-excretory/secretory (ES) antigen IgE and IgG responses in CSF were analyzed. In addition, the antibody-dependent eosinophil-mediated cytotoxicity induced by anti-excretory/secretory (ES) antigen antibodies may be the reason of severe brain inflammation in infected BALB/c mice. IgE and IgG antibodies against a 105 kDa protein of L5 antigen was detected at week 3 post-infection in C57BL/6 mice and week 5 post-infection in BALB/c mice. We suggest that 105 kDa protein is related with the antibody response of A. cantonensis-infected mice. CONCLUSION: We found that IgE antibodies in mice CSF against L5 antigens related to worm rejection in mice brains. This study may help to identify specific angiostrongyliasis markers that can be applied for clinical diagnosis and treatment in future.

Decellularized tendon scaffolds loaded with collagen targeted extracellular vesicles from tendon-derived stem cells facilitate tendon regeneration.

Stem cell-based treatment of tendon injuries remains to have some inherent issues. Extracellular vesicles derived from stem cells have shown promising achievements in tendon regeneration, though their retention in vivo is low. This study reports on the use of a collagen binding domain (CBD) to bind extracellular vesicles, obtained from tendon-derived stem cells (TDSCs), to collagen. CBD-extracellular vesicles (CBD-EVs) were coupled to decellularized bovine tendon sheets (DBTS) to fabricate a bio-functionalized scaffold (CBD-EVs-DBTS). Our results show that thus obtained bio-functionalized scaffolds facilitate the proliferation, migration and tenogenic differentiation of stem cells in vitro. Furthermore, the scaffolds promote endogenous stem cell recruitment to the defects, facilitate collagen deposition and improve the biomechanics of injured tendons, thus resulting in functional regeneration of tendons.

Climate change and mortality rates of COPD and asthma: A global analysis from 2000 to 2018.

BACKGROUND: Climate change plays a significant role in global health threats, particularly with respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, but the long-term global-scale impact of climate change on these diseases' mortality remains unclear. OBJECTIVE: This study aims to investigate the impact of climate change on the age-standardized mortality rates (ASMR) of COPD and asthma at national levels. METHODS: We used Global Burden of Disease (GBD) data of ASMR of COPD and asthma from 2000 to 2018. The climate change index was represented as the deviance percentage of temperature (DPT) and relative humidity (DPRH), calculated based on 19-year temperature and humidity averages. Annual temperature, RH, and fine particulate matter (PM2.5) levels in 185 countries/regions were obtained from ERA5 and the OECD's environmental statistics database. General linear mixed-effect regression models were used to examine the associations between climate change with the log of ASMR (LASMR) of COPD and asthma. RESULTS: After adjusting for annual PM2.5, SDI level, smoking prevalence, and geographical regions, a 0.26% increase in DPT was associated with decreases of 0.016, 0.017, and 0.014 per 100,000 people in LASMR of COPD and 0.042, 0.046, and 0.040 per 100,000 people in LASMR of asthma for both genders, males, and females. A 2.68% increase in DPRH was associated with increases of 0.009 and 0.011 per 100,000 people in LASMR of COPD. We observed a negative association of DPT with LASMR for COPD in countries/regions with temperatures ranging from 3.8 to 29.9 °C and with LASMR for asthma ranging from -5.3-29.9 °C. However, we observed a positive association of DPRH with LASMR for both COPD and asthma in the RH range of 41.2-67.2%. CONCLUSION: Climate change adaptation and mitigation could be crucial in reducing the associated COPD and asthma mortality rates, particularly in regions most vulnerable to temperature and humidity fluctuations.

An Integrative Explainable Artificial Intelligence Approach to Analyze Fine-Scale Land-Cover and Land-Use Factors Associated with Spatial Distributions of Place of Residence of Reported Dengue Cases.

Dengue fever is a prevalent mosquito-borne disease that burdens communities in subtropical and tropical regions. Dengue transmission is ecologically complex; several environmental conditions are critical for the spatial and temporal distribution of dengue. Interannual variability and spatial distribution of dengue transmission are well-studied; however, the effects of land cover and use are yet to be investigated. Therefore, we applied an explainable artificial intelligence (AI) approach to integrate the EXtreme Gradient Boosting and Shapley Additive Explanation (SHAP) methods to evaluate spatial patterns of the residences of reported dengue cases based on various fine-scale land-cover land-use types, Shannon's diversity index, and household density in Kaohsiung City, Taiwan, between 2014 and 2015. We found that the proportions of general roads and residential areas play essential roles in dengue case residences with nonlinear patterns. Agriculture-related features were negatively associated with dengue incidence. Additionally, Shannon's diversity index showed a U-shaped relationship with dengue infection, and SHAP dependence plots showed different relationships between various land-use types and dengue incidence. Finally, landscape-based prediction maps were generated from the best-fit model and highlighted high-risk zones within the metropolitan region. The explainable AI approach delineated precise associations between spatial patterns of the residences of dengue cases and diverse land-use characteristics. This information is beneficial for resource allocation and control strategy modification.

Corrigendum: Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches.

[This corrects the article DOI: 10.3389/fmicb.2023.1126418.].

Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches.

The emergence of potentially life-threatening zoonotic malaria caused by Plasmodium knowlesi nearly two decades ago has continued to challenge Malaysia healthcare. With a total of 376 P. knowlesi infections notified in 2008, the number increased to 2,609 cases in 2020 nationwide. Numerous studies have been conducted in Malaysian Borneo to determine the association between environmental factors and knowlesi malaria transmission. However, there is still a lack of understanding of the environmental influence on knowlesi malaria transmission in Peninsular Malaysia. Therefore, our study aimed to investigate the ecological distribution of human P. knowlesi malaria in relation to environmental factors in Peninsular Malaysia. A total of 2,873 records of human P. knowlesi infections in Peninsular Malaysia from 1st January 2011 to 31st December 2019 were collated from the Ministry of Health Malaysia and geolocated. Three machine learning-based models, maximum entropy (MaxEnt), extreme gradient boosting (XGBoost), and ensemble modeling approach, were applied to predict the spatial variation of P. knowlesi disease risk. Multiple environmental parameters including climate factors, landscape characteristics, and anthropogenic factors were included as predictors in both predictive models. Subsequently, an ensemble model was developed based on the output of both MaxEnt and XGBoost. Comparison between models indicated that the XGBoost has higher performance as compared to MaxEnt and ensemble model, with AUCROC values of 0.933 ± 0.002 and 0.854 ± 0.007 for train and test datasets, respectively. Key environmental covariates affecting human P. knowlesi occurrence were distance to the coastline, elevation, tree cover, annual precipitation, tree loss, and distance to the forest. Our models indicated that the disease risk areas were mainly distributed in low elevation (75-345 m above mean sea level) areas along the Titiwangsa mountain range and inland central-northern region of Peninsular Malaysia. The high-resolution risk map of human knowlesi malaria constructed in this study can be further utilized for multi-pronged interventions targeting community at-risk, macaque populations, and mosquito vectors.

Differential expression of glucose metabolism-related genes and AMP-activated protein kinases in crop tissue of male and female pigeons (Columba livia domestica) during the incubation and chick-rearing periods.

The objective of this study was to explore the carbohydrate contents of crop milk, insulin and glucose concentrations in serum and the expression patterns of AMP-activated protein kinases (AMPKs) and genes related to glucose metabolism in pigeon crops during the breeding period. Crop milk was collected from squabs of rearing Day 1 (R1) to R6. Contents of total sugar and reducing sugar increased to the maximum levels at R6 (p < 0.05). Forty-two pairs of adult pigeons were allotted to seven groups by different breeding stages, and their crops and serum were sampled. No significant differences were found in either insulin or glucose levels in serum. The glucose transporter 2 gene level was the greatest at R15 in females, whereas it was at R7 in males. However, sodium-dependent glucose transporters 1 expression in both sexes decreased from incubation Day 17 (I17) to R7. In females, glucokinase expression peaked at R1, and at R1 and R7 in males. Pyruvate kinase mRNA levels peaked at R7 in females and at R15 males. The mRNA abundance of fructose-1,6-bisphosphatase 1 in both sexes and glucose-6-phosphatase in females decreased after I10. While phosphoenolpyruvate carboxykinase 1 expression decreased after I17 (p < 0.05). Protein levels of AMPKα in crops were minimized at R1 (p < 0.05). In females, expression of AMPKα1 and AMPKα2 was inhibited at I17 and R1 (p < 0.05). In males, AMPKα1 expression was decreased at R7 (p < 0.05) and AMPKα2 was reduced at I10 and R1. pAMPK expression was the lowest at I17 in females, and it was at R7 and R25 in males. Conclusively, glycolysis in pigeon crops was enhanced during chick-rearing, while gluconeogenesis was significantly inhibited. The stability of the insulin level suggests that it was probably not involved in the regulation of glucose metabolism in crop tissues.

Comparison of growth and quality of wild and cultivated Artemisia stolonifera / 中国中药杂志

This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.

Effects of shading intensity on growth and quality of Artemisia stolonifera / 中国中药杂志

The purpose of this study was to analyze the effects of shading intensity on the growth, yield, and quality of Artemisia stolonifera so as to provide references for the artificial cultivation of A. stolonifera. The seedlings of A. stolonifera with consistent growth underwent shading treatment at four shading intensity levels(0, 55%, 85%, and 95%) with different layers of black shading nets. The agronomic indexes, yield, moxa yield, total ash, quality characteristics of moxa during combustion and pyrolysis, main volatile components, flavonoids, and phenolic acids were measured. The results showed that under shading conditions, the stem diameter, leaf width, 5-leaf spacing, branch number, and yield of A. stolonifera decreased significantly, while the plant height, leaf length, leaf number, chlorophyll content, and moxa yield increased first and then decreased with the increase in shading intensity. The burning performance of moxa under natural light was better than that under moderate and severe shading conditions. The content of eucalyptol first increased and then decreased with the increase in shading intensity. The humulene content was negatively correlated with shading intensity. Other major volatile components showed no significant difference under various shading conditions. The content of neochlorogenic acid, cryptochlorogenic acid, isoschaftoside, and isochlorogenic acid B was positively correlated with shading intensity, while the content of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C decreased first and then increased with the increase in shading intensity. To sum up, A. stolonifera is a light-loving plant, and shading can greatly reduce the yield, the content of internal components, and the burning performance of moxa. It is the main reason why A. stolonifera is mainly distributed in the forest edge, open forest, roadside, and wasteland grass in the middle and high mountains in the wild. For artificial domestication and cultivation of A. stolonifera, it is better to select plots with sufficient light.

Research progress in the protective efficacy of human papillomavirus vaccines in males / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is one of the most common sexually transmitted pathogens. It can cause a variety of diseases such as condyloma acuminatum, anal cancer, penile cancer and oropharyngeal cancer in men, resulting in a high disease burden. With the development of society, the application of HPV vaccines in males has attracted more attention. Currently, there are many clinical trials and real-world research results of HPV vaccines applied to boys and men worldwide, and many countries have introduced HPV vaccination for underage boys into their national immunization programs. This article intended to review the research progress in the efficacy of HPV vaccines in male population.

Effectiveness of HPV vaccines in real-world study / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is an epitheliotropic virus. High-risk HPV infections lead to precancerous lesions which may progress to cancer in the cervix, vagina and vulva, while low-risk HPV infections cause benign lesions such as genital warts and recurrent respiratory papillomas. HPV infection remains one of the major public health problems threatening human health. To date, six prophylactic preventive HPV vaccines have been licensed, and the effectiveness of HPV vaccination has gradually appeared in some countries with earlier vaccination. HPV vaccination has been proved to be effective in protecting against diseases related to HPV infection, which leads to significant reductions in the incidence of vaccine-type HPV-related infection, high cervical lesions, anogenital warts, recurrent respiratory papillomatosis and other relevant diseases. The herd protection effect of the vaccines is outstanding. Meanwhile, a bivalent HPV vaccine has been demonstrated for the cross-protection against HPV infections of non-vaccine types (HPV31/33/45) in real-world vaccination practice.

Early neurological deterioration in patients with minor ischemic stroke caused by large vessel occlusion: risk factors and the impact of rescue endovascular thromboectomy on outcomes at discharge / 国际脑血管病杂志

Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.

Effects of activating mTORC2/Akt signaling pathway on dopaminergic neurons and behaviors in 6-hydroxydopamin model mice / 解剖学报

Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.

Effect and molecular mechanism of mammalian target of rapamycin complex 2 / Akt signaling pathway on 6-hydroxydopamine-treated SH-SY5Y cell model / 解剖学报

[Abstract] Objective To study whether the regulation of mammalian target of rapamycin complex 2(mTORC2) / Akt signaling pathway has a protective effect on SH-SY5Y cell line damaged by 6-hydroxydopamine (6-OHDA), and to clarify its molecular mechanism. Methods SH-SY5Y cells treated with retinoic acid (RA) were given 6-OHDA, mTORC2 signaling pathway inhibitor PP242 and agonist A-443654 respectively. The changes of cell number in each group were investigated by immunofluorescent staining; The total protein was extracted and the expression level and interaction of key proteins in mTORC2 signaling pathway were determined by Western blotting and co-immunoprecipitation (CoIP); The apoptosis rate of cells in each group was detected by flow cytometry. At the same time, the co-culture Parkinson’ s disease (PD) model was made using SH-SY5Y cell line and Bv-2 cell line; MTT colorimetric method was used to detect the cell viability of each group; ELISA was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cell culture supernatant. Results The number of tyrosine hydroxylase(TH) / proliferating cell nuclear antigen (PCNA) / hochest-, TH / 5-bronmo-2’ -deoxyuridine(BrdU) -labeled positive cells in 6-OHDA-lesioned PD cell model group was significantly lower than that in the normal group; The apoptosis rate was higher; The expression of Rictor, p-Akt and regulated in DNA damage and development 1(REDD1) was increased; There was an interaction between Rictor and p-Akt or REDD1; The cell viability was significantly reduced in the co-culture model; the content of TNF-α and IL-β increased in the cell culture supernatant. With further up-regulation of the abovementioned protein expressions, the cell survival, apoptosis and pro-inflammatory cytokine levels in A-443654 group were significantly ameliorated, while PP242 group showed the opposite changes. Conclusion A-443654 activates mTORC2 signaling pathway by p-Akt, which increases the expression of Rictor and REDD1 protein. These changes contribute to the amelioration in cell survival rate, apoptosis rate, and the proliferation and differentiation and decreasion of apoptosis rate of SH-SY5Y cells. These result improved 6-OHDA-induced cell damage and inhibited the release of pro-inflammatory cytokines.

Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism / 中国中药杂志

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.