BACKGROUND:Bone marrow mesenchymal stem cells possess multipotent differentiation potential and are an important source of cells for cartilage and bone tissue regeneration research.Kartogenin is a small-molecule drug that has been demonstrated to promote stem cell differentiation towards chondrogenesis.However,the ability to promote osteogenic differentiation is still controversial,and the specific effects of kartogenin on the chondrogenic and osteogenic differentiation of stem cells of different species have not been fully elucidated.OBJECTIVE:To investigate the effects of kartogenin on chondrogenic and osteogenic differentiation in rabbit-derived and rat-derived bone marrow mesenchymal stem cells.METHODS:Rabbit-derived and rat-derived bone marrow mesenchymal stem cells were obtained through whole bone marrow separation and adherence methods,and were treated with varying concentrations of kartogenin.Cell proliferation was detected using the CCK-8 assay.Chondrogenic and osteogenic differentiation was assessed via toluidine blue and alizarin red staining,respectively.After screening for the optimal concentration of kartogenin,alkaline phosphatase staining,qRT-PCR,and western blot assay were employed to analyze the expression of osteogenic and chondrogenic-related genes and proteins.RESULTS AND CONCLUSION:(1)Within the concentration range of 0 to 10 000 nmol/L,kartogenin did not significantly affect the proliferation of rabbit-derived or mouse-derived bone marrow mesenchymal stem cells.(2)The differentiation effect of kartogenin on rabbit-derived and rat-derived bone marrow mesenchymal stem cells showed significant differences.In rabbit-derived bone marrow mesenchymal stem cells,kartogenin predominantly promoted chondrogenic differentiation while inhibiting osteogenic differentiation.This was evident from positive toluidine blue staining,whereas alkaline phosphatase and alizarin red staining exhibited no significant changes.qRT-PCR analysis revealed upregulation of chondrogenic-related genes(Col2a1 and Sox9)and downregulation of genes associated with osteogenesis(Alpl,Col1a1,Runx2,and Bglap).Similar results were found in the western blot assay.(3)In contrast,kartogenin in mouse-derived bone marrow mesenchymal stem cells promoted both chondrogenic and osteogenic differentiation.While toluidine blue staining remained largely unchanged,alkaline phosphatase and alizarin red staining revealed increased positivity,indicative of enhanced osteogenesis.qRT-PCR analysis showed upregulation of not only chondrogenic-related genes(Col2a1 and Sox9)but also genes linked to osteogenesis(Alpl,Col1a1,Runx2,and Bglap).The western blot assay results showed similar results.These findings suggest that kartogenin exerts differential regulatory effects on the differentiation of rabbit and rat bone marrow mesenchymal stem cells,potentially stemming from variations in gene expression profiles and underlying signaling pathways.

BACKGROUND:Bone marrow mesenchymal stem cells possess multipotent differentiation potential and are an important source of cells for cartilage and bone tissue regeneration research.Kartogenin is a small-molecule drug that has been demonstrated to promote stem cell differentiation towards chondrogenesis.However,the ability to promote osteogenic differentiation is still controversial,and the specific effects of kartogenin on the chondrogenic and osteogenic differentiation of stem cells of different species have not been fully elucidated.OBJECTIVE:To investigate the effects of kartogenin on chondrogenic and osteogenic differentiation in rabbit-derived and rat-derived bone marrow mesenchymal stem cells.METHODS:Rabbit-derived and rat-derived bone marrow mesenchymal stem cells were obtained through whole bone marrow separation and adherence methods,and were treated with varying concentrations of kartogenin.Cell proliferation was detected using the CCK-8 assay.Chondrogenic and osteogenic differentiation was assessed via toluidine blue and alizarin red staining,respectively.After screening for the optimal concentration of kartogenin,alkaline phosphatase staining,qRT-PCR,and western blot assay were employed to analyze the expression of osteogenic and chondrogenic-related genes and proteins.RESULTS AND CONCLUSION:(1)Within the concentration range of 0 to 10 000 nmol/L,kartogenin did not significantly affect the proliferation of rabbit-derived or mouse-derived bone marrow mesenchymal stem cells.(2)The differentiation effect of kartogenin on rabbit-derived and rat-derived bone marrow mesenchymal stem cells showed significant differences.In rabbit-derived bone marrow mesenchymal stem cells,kartogenin predominantly promoted chondrogenic differentiation while inhibiting osteogenic differentiation.This was evident from positive toluidine blue staining,whereas alkaline phosphatase and alizarin red staining exhibited no significant changes.qRT-PCR analysis revealed upregulation of chondrogenic-related genes(Col2a1 and Sox9)and downregulation of genes associated with osteogenesis(Alpl,Col1a1,Runx2,and Bglap).Similar results were found in the western blot assay.(3)In contrast,kartogenin in mouse-derived bone marrow mesenchymal stem cells promoted both chondrogenic and osteogenic differentiation.While toluidine blue staining remained largely unchanged,alkaline phosphatase and alizarin red staining revealed increased positivity,indicative of enhanced osteogenesis.qRT-PCR analysis showed upregulation of not only chondrogenic-related genes(Col2a1 and Sox9)but also genes linked to osteogenesis(Alpl,Col1a1,Runx2,and Bglap).The western blot assay results showed similar results.These findings suggest that kartogenin exerts differential regulatory effects on the differentiation of rabbit and rat bone marrow mesenchymal stem cells,potentially stemming from variations in gene expression profiles and underlying signaling pathways.

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

Glioblastoma (GBM) is an exceptionally aggressive tumor that originates in the brain,characterized by a notably high mortality rate and a limited responsiveness to pharmacological interven-tions.In recent years,antibody-drug conjugates (ADCs) have emerged as a focal point in the advance-ment of anti-cancer therapeutic research,merging the precise targeting capabilities of antibodies with the powerful killing power of cytotoxins.In recent years,the outcomes of numerous clinical trials investi-gating ADCs targeted against GBM have been notably encouraging.This article endeavors to provide a comprehensive overview of the prevalent ADCs targets for GBM therapy,which include the epidermal growth factor receptor,the cluster of differentiation,the mannose receptor family,the integrin family,and the galectin family.Furthermore,it will delve into the contemporary landscape of ADCs drug research and the significant challenges encountered in the application of ADCs for GBM treatment.

Glioblastoma (GBM) is an exceptionally aggressive tumor that originates in the brain,characterized by a notably high mortality rate and a limited responsiveness to pharmacological interven-tions.In recent years,antibody-drug conjugates (ADCs) have emerged as a focal point in the advance-ment of anti-cancer therapeutic research,merging the precise targeting capabilities of antibodies with the powerful killing power of cytotoxins.In recent years,the outcomes of numerous clinical trials investi-gating ADCs targeted against GBM have been notably encouraging.This article endeavors to provide a comprehensive overview of the prevalent ADCs targets for GBM therapy,which include the epidermal growth factor receptor,the cluster of differentiation,the mannose receptor family,the integrin family,and the galectin family.Furthermore,it will delve into the contemporary landscape of ADCs drug research and the significant challenges encountered in the application of ADCs for GBM treatment.

Objective: To explore the relationship between processed food consumption and blood pressure level of students in a university in Yunnan Province, so as to provide the reference for preventing hypertension in university students. Methods: In October 2021, a cluster sampling method was used to select 4 781 freshmen from a university in Kunming, Yunnan Province. The frequency of processed food consumption of university students was assessed by using the dietary frequency questionnaire, and height, weight and blood pressure were measured. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences in blood pressure level of university students with different demographic variables, and the association between processed food consumption and blood pressure level was analyzed with a generalized linear model. Results: Among the students of a university in Yunnan Province, the detection rates of systolic prehypertension and hypertension were 33.86% and 1.23%, and the detection rates of diastolic prehypertension were 32.13% and hypertension 7.22%. The results of generalized linear model analysis showed that after controlling for demographic variables and other variables that might affect the blood pressure level of university students, the consumption of processed food (bread and cake: β =0.15, 95% CI =0.01-0.29) and ultra processed food (coffee beverage: β =-0.29, 95% CI =-0.54--0.03) were associated with systolic blood pressure level( P <0.05). The consumption of processed food (salted duck egg: β =0.21, 95% CI =0.01-0.41) was correlated with the diastolic blood pressure of college students ( P <0.05). Conclusions Processed food consumption in university students may increase the risk of high blood pressure.The education of healthy eating among college students should be strengthened to reduce the consumption of processed foods.

Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P＞0.99),and there was statistically significant difference in ADC values between the other groups(P＜0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95％confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95％CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.