Latest ArticlesTo observe the influences of ginsenoside Rb1 （GsRb1） on the proliferation and osteogenic differentiation of human periodontal ligament stem cells （hPDLSCs）, and its molecular mechanism related to stromal cell-derived factor-1 （SDF-1）/CXC chemokine receptor 4 （CXCR4） pathway.
hPDLSCs were isolated and cultured by enzyme digestion method. Cell morphology was observed under an inverted microscope. Flow cytometry was used to detect the proportion of stromal cell antigen 1 （STRO-1） and cluster of differentiation 146 （CD146） positive cells. hPDLSCs were treated with 0, 0.5, 1.0, 2.0, 4.0, 6.0 μmol·L-1 GsRb1, respectively, and the optimal concentration was screened by CCK-8 method. hPDLSCs were divided into control group, GsRb1 （4.0 μmol·L-1） group, AMD3100 （5 μg·mL-1） group, and GsRb1+AMD3100 group, the cell proliferation and alkaline phosphatase （ALP） activity of each group were compared, the mRNA expression of Runt-related gene 2 （Runx2）, oxterix, and osteopontin （OPN） were detected by qRT-PCR, and the formation of mineralized nodules in hPDLSCs was detected by alizarin red staining and quantitative analysis. Western blot was used to detect the expression of SDF-1/CXCR4 signaling pathway-related proteins.
hPDLSCs were arranged radially, with long spindles, and the growth was relatively dense. The proportions of STRO-1 and CD146 positive cells were 97.19% and 98.01%, respectively. With the increase of GsRb1 concentration, the proliferation activity of hPDLSCs was enhanced in a dose-dependent manner （P<0.05）. Compared with the control group, the cell viability and ALP activity in the GsRb1 group were enhanced, and the mRNA expression of Runx2, oxterix, OPN, the amount of mineralized nodules, and the protein expression of SDF-1 and CXCR4 were increased （P<0.05）, while the AMD3100 group was the opposite （P<0.05）.Compared with the GsRb1 group, the cell viability and ALP activity in the GsRb1+AMD3100 group were decreased, and the mRNA expression of Runx2, oxterix, OPN, the amount of mineralized nodules, and the protein expression of SDF-1 and CXCR4 were decreased （P<0.05）.
GsRb1 can promote the proliferation and osteogenic differentiation of hPDLSCs, which may be related to the increased protein expression of SDF-1/CXCR4 signaling pathway.
In order to establish a technical evaluation system in line with the characteristics of traditional Chinese medicine （TCM） and promote the inheritance and innovative development of TCM, China is building a TCM registration and evaluation evidence system combining TCM theory, human experience, and clinical trials. Human experience is of great significance to support the registration and evaluation of new drugs of TCM. Based on the survey of 20 medical institutions in Shanghai, this paper analyzed the current situation and common problems of human experience collection of TCM. It was found that medical institutions had been aware of carrying out human experience collection for the development of TCM preparations or new drugs. However, the hardware conditions, personnel capabilities, and the importance of medical institutions in collecting human experience were still not optimistic. There were difficulties in the collection process. 90%of institutions believed that the quality of collected data did not meet the requirements of drug registration. Regulators and medical institutions should work together to improve and standardize the collection of human experience of TCM by improving collection methods, increasing research capabilities, strengthening the construction of information systems, and enhancing research quality management according to GCP principles, so as to ultimately obtain high-quality evidence materials to support the innovation and transformation of TCM.
Glutamine （Gln） is the key carbon and nitrogen donor and energy source of the body. It is not only a critical player in tumorigenesis but also involved in regulating the development and activation of immune cells. Rapidly proliferating tumor cells will obtain a large amount of nutrients from the tumor microenvironment, leading to depletion of Gln, which significantly inhibits the activity and function of T cells and induces T cell exhaustion. The proliferation of tumor cells was suppressed by Gln metabolism inhibitors, including Gln mimetics, glutaminase inhibitors，and Gln transporter inhibitors. Meanwhile, T cell depletion was not further aggravated. Instead, the tumor microenvironment was improved to enhance the antitumor immune response by regulating multiple mechanisms such as immune checkpoint molecule expression,extracellular matrix structure remodeling, and tumor-associated macrophage polarization. Combining Gln metabolic inhibitors with immune checkpoint inhibitors can also exert synergistic effects.
To study the protective effect of cerebroprotein hydrolysate and its related mechanism of regulating endoplasmic reticulum stress in ischemic stroke based on network pharmacology and animal experiments.
GeneCards and OMIM databases were used to screen the targets related to ischemic stroke and endoplasmic reticulum stress, and Wayne diagram was drawn to get the intersection genes. The protein-protein interaction network diagram was downloaded from String database and visualized by Cytoscape software, and the top 10 genes were screened by cytoHubba plug-in. Finally, Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） were enriched and analyzed. Mouse models of ischemic stroke were made by the suture-occluded method, and randomly divided into sham group, model group, cerebroprotein hydrolysate 0.2 g·kg-1 group and 0.5 g·kg-1 group, and edaravone 8 mg·kg-1 group,with 11 mice in each group. The drug was administered continuously for 5 days after operation. The volume of cerebral infarction was measured by TTC staining, the contents of interleukin （IL）-6, IL-1β, γ-interferon （IFN-γ） and brain-derived neurotrophic factor （BDNF） in cerebral ischemic penumbra and serum were measured by ELISA, and the expression of Caspase-3 and AKT protein in brain tissue was observed by immunohistochemistry.
According to the results of network pharmacology, 41 intersection genes of ischemic stroke and endoplasmic reticulum stress were screened, and the top 10 genes screened were IL-6, ALB, INS, TNF, AKT1, CASP3, MAPK3, TP53, SIRT1 and VEGFA, respectively. GO enrichment resulted in 515 related entries. KEGG pathway enrichment involved lipid and atherosclerosis pathway, human cytomegalovirus infection, Alzheimer’s disease, phosphatidylinositol -3- kinase/ protein kinase B （PI3K/AKT） signaling pathway and so on. Compared with the model group, the cerebral infarction volume was significantly reduced （P<0.01）; the contents of IL-6, IL-1β and IFN-γ in serum and penumbra were decreased significantly （P<0.05）, and the contents of BDNF in serum and penumbra were increased significantly （P<0.05）; the expression of Caspase-3 in brain tissue was decreased significantly （P<0.05）, and the expression of AKT was increased significantly （P<0.05） in the two groups of cerebroprotein hydrolysate.
Based on the analysis of network pharmacology, the endoplasmic reticulum stress mechanism of ischemic stroke may be related to inflammation and apoptosis. The neuroprotective mechanism of cerebroprotein hydrolysate may be related to activating BDNF/PI3K/AKT pathway and inhibiting inflammation and apoptosis.
CD34+ cells have microcirculatory regenerative potential and paracrine anti-inflammatory effects, but the number and function of CD34+ cells involved in vascular repair are decreased in patients with heart failure. Multiple trials have found that CD34+cell transplantation therapy in patients with chronic heart failure can improve myocardial performance, reduce neurohumoral activation, improve exercise capacity and quality of life, and even improve the survival rate in patients with heart failure. CD34+ cell transplantation may be a future treatment option for patients with chronic heart failure.
To explore the effects of berberine on intestinal injury in sepsis rats and its mechanism.
Forty male healthy SD rats were randomly divided into sham group, model group, berberine low, medium, and high dose (25, 50, 100 mg·kg-1) groups, with 8 rats in each group, and the corresponding dose was given by gavage for 7 d. Sepsis model was prepared by cecum ligation and perforation (CLP). After 24 h of modeling, the rats were anesthetized and the ileum specimens were collected. The pathological changes of the ileum were observed and scored under light microscope. The contents of serum heme oxygenase-1 (HO-1), diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), interleukin (IL) -6 and IL-1β were detected by ELISA. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in ileum were detected by colorimetric analysis. The protein levels of HO-1, nuclear factor E2-related factor 2 (Nrf2) and IL-1β in ileum were detected by Western blot.
Compared with the sham group, ileum histopathological score was significantly increased in the model group (P<0.01), and contents of HO-1, IL-1β, IL-6, TNF-α, DAO, iFABP in serum, and MDA in intestinal tissue were increased, while SOD activity was decreased, and the expressions of Nrf2, HO-1 and IL-1β protein in the model group were significantly increased (P<0.01). Compared with the model group, the ileum histopathologic score of the berberine high dose group was significantly decreased (P<0.01), the contents of IL-1β, IL-6, TNF-α, DAO, iFABP in serum and MDA in intestinal tissue were also decreased (P<0.05), while the HO-1 content in serum and SOD activity in intestinal tissue were increased (P<0.01), and the protein expressions of Nrf2 and HO-1 in the berberine high dose group were significantly increased, but the IL-1β protein expression was decreased (P<0.05).
Berberine can effectively improve intestinal damage caused by sepsis, and its mechanism may be related to the up-regulation of Nrf2/HO-1 expression.
Alzheimer’s disease (AD) is the most common form of irreversible dementia. In addition to assessing of patients’ memory abilities, positron emission tomography (PET), as a non-invasive diagnostic modality with high sensitivity and qualitative or quantitative imaging of the target sites, can qualitatively and quantitatively evaluate β-amyloid (Aβ), tau proteins, synaptic proteins, and other related biomarkers, which is of great significance in the diagnosis of AD. As PET imaging approved by FDA, [18F]-flutemetamol, a derivative of 18F labelled thioflavin-T, and [18F]-florbetaben, [18F]-florbetapir, which are phenylpyridine derivates, have high specificity in their affinity for Aβ plaque binding. Other radionuclides such as 68Ga and 64Cu labeled radiotracers also showed high affinity with Aβ plaques. Quinoline derivatives [18F]-THK5351, [18F]-PPQ8, benzimidazolopyrimidine and pyridine-indole derivatives [18F]-T807, and lansoprazole derivatives [11C]-NML as PET imaging agents, can quantify tau protein tangles. And the structural derivatives of levetiracetam [11C]-UCB-J and [18F]-SDM-8 can measure synaptic density, while the structural derivatives [18F]-FPEB of 3-fluoro-4-acetylidene-benzylnitrile can assist in the diagnosis of AD by binding with mGluR5. The fluorobenzoyl derivative [18F]-altanserin, with ketoserin as its structural parent, acts on 5-hydroxytryptamine to study the molecular changes of early AD.
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor that occurs in the biliary system, with a hidden onset, poor overall prognosis and high mortality. Futibatinib is a fibroblast growth factor receptor (FGFR) 1-4 inhibitor, which was approved by the U.S. Food and Drug Administration in 2022 for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic ICC with FGFR2 gene fusions or other rearrangements. Phase Ⅰ and Ⅱ clinical trials have shown that futibatinib has good clinical effect on ICC, which can significantly improve the objective response rate and prolong the survival time of ICC patients. The common adverse events include hyperphosphatemia, diarrhea, constipation, and dry mouth, with a high incidence of adverse events.
To investigate the potentially inappropriate medications (PIM) in elderly patients with hypertension combined with cerebral infarction and to develop a nomogram model based on Lasso-logistic regression of the influencing factors.
A total of 105 patients with hypertension combined with cerebral infarction and multi-drug therapy discharged from January to December 2020 were included，and the PIM was evaluated by the criteria of potentially inappropriate medications for older adults in China. The PIM influencing factors were analyzed by Lasso-logistic regression, Nomogram model of factors influencing the PIM risk was developed, and the discrimination and accuracy of the model were evaluated.
The incidence of PIM in 105 patients of hypertension complicated with cerebral infarction was 85 cases (81.0%) and 184 times, involving 26 drugs. The 1st drug was clopidogrel with 48 times (26.1%). A statistically significant effect of the number of drugs (P=0.003, OR=1.412, 95% CI: 0.582 to 2.868) and diabetes (P<0.001, OR=0.081, 95% CI: -3.899 to -1.129) on PIM was suggested by the Lasso-logistic regression. Of the model, a good accuracy and discrimination was suggested by the area under the ROC curve (AUC), which was 85.3% (95% CI: 0.772 to 0.933), and an acceptable predictive power was suggested by internal validation with Bootstrap method (B=1 000).
The nomogram model based on Lasso-logistic regression can better identify the risk of PIM. Elderly patients with hypertension complicated with cerebral infarction and multi-drug therapy have a high risk of PIM, and it is necessary to reduce the number of medications to reduce the risk of PIM.
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