Latest ArticlesTo study the anti-tumor effect of icotinib combined with metformin on non-small cell lung cancer （NSCLC） H1975 cells and its possible mechanism.
CCK-8 assay was used to detect the proliferation inhibitory effect and combination index （CI） of icotinib monotherapy （0, 0.1, 1, 5, 10, 20, 40 μmol·mL-1）, metformin monotherapy （0, 2, 4, 8, 16, 32, 64 mmol·mL-1）, and icotinib （0, 0.125, 0.25, 0.5, 1 times of IC50） combined with metformin （0.5 times of IC50） on the H1975 cells. The migratory ability of the cells was detected by scratch test，and the invasive ability of the cells was detected by invasion test. Annexin V-FITC/PI flow cytometry was used to detect the rate of apoptosis. Western blot was used to detect the expression level of related proteins.
The IC50 of icotinib and metformin for the inhibition on H1975 cells after 48 h were （49.90±4.84） μmol·mL-1 and （13.20±1.27）mmol·mL-1, respectively. Icotinib and metformin produced a synergistic effect in H1975 cells（CI<1）. Compared with the metformin group and the icotinib group, the migration rate and invasion ability of combination group were significantly decreased, and the apoptosis rate was significantly increased （P<0.05）；the expression of p-Akt, p-mTOR and Bcl-2 were significantly decreased, while the expression of p-AMPK and Bax were significantly increased （P<0.05）.
Icotinib and metformin have significant synergic antitumor effects and proapoptotic effects on non-small cell lung cancer H1975 cells, and the underlying mechanism may be related to enhancing activation of AMPK and inhibition of Akt/mTOR signaling pathway.
To study the antibacterial mechanism of palmatine based on network pharmacology, molecular docking, and molecular dynamics.
The drug targets of palmatine were predicted through the Swiss Target Prediction website, and the potential antibacterial targets of palmatine were obtained by mapping them with the antibacterial targets retrieved from GeneCards and OMIM databases. Protein-protein interaction network was constructed using STRING database and Cytoscape software and key targets were screened. The DAVID database was used to carry out Gene Ontology（GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of potential targets, and visual processing was performed to build the “Component-Target-Pathway” network of palmatine. The binding of palmatine to key targets was validated through molecular docking and molecular dynamics simulations. In vitro antibacterial experiments were conducted to verify the antibacterial activity of palmatine.
A total of 28 critical anti-bacterial targets of palmatine were screened and enriched to 199 GO entries and 105 related pathways. “Ingredients-Target-Pathway”network showed that MAPK8, RAC1, and STAT3 were key anti-bacterial targets.The molecular docking results indicated that palmatine had an excellent binding effect with key targets MAPK8 and RAC1. Molecular dynamics studies found that there were hydrogen bonds and hydrophobic interactions between palmatine and proteins, enabling stable binding of palmatine to target proteins. In vitro antibacterial experiments showed that palmatine had strong inhibitory activity against Staphylococcus aureus and Candida albicans, and it had synergistic effects when combined with positive drugs.
Palmatine may exert its antibacterial effects by inhibiting the gene expression of MAPK8 and RAC1 through endocrine resistance and signaling pathways such as PI3K-Akt and FoxO.
To analyze the general patterns and characteristics of osimertinib related interstitial lung disease（ILD）.
The case reports of osimertinib related ILD from CNKI, VIP, Wanfang and PubMed database between November 2015 to June 2023 were searched and analyzed.
A total of 25 case reports were enrolled,involving 28 cases with ILD, 14 male and 14 female cases, aged 32 to 86 years old. PD-1 inhibitors were used sequentially in 4 patients before administering osimertinib, 21 patients developed ILD in 3 months, 25 patients experienced symptom relief after discontinuation reduction medication, and 3 patients died.
ILD should be closely guarded in 3 months of the application of osimertinib, especially these patients who received the sequence treatment of PD-1 inhibitors.The key to improving the prognosis is to stop using osimertinib immediately after ILD.
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 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.
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.
To investigate the effect of canagliflozin on liver cancer cells and its regulatory mechanism.
The effects of canagliflozin on the proliferation of liver cancer cell HepG2, Huh7 and HCCM were detected by cell clone formation assay and CCK-8 assay. Flow cytometry was used to measure changes in reactive oxygen species (ROS) levels, both intracellular and mitochondrial ROS levels, as well as alterations in mitochondrial membrane potential. Western blot was employed to assess the expression of proteins related with proliferation and cGAS-STING pathway. Mitochondrial DNA (mtDNA) release and inflammatory factor mRNA expression level were detected by RT-qPCR.
Compared with human normal liver cell MIHA, the inhibitory effect of canagliflozin on HepG2 cell proliferation was more significant (P<0.05，semi-inhibitory concentrations were >40 μmol·L-1 and 15 μmol·L-1, respectively). Compared with the control group, the clone number of liver cancer cells and the expression of proliferation-related proteins in the canagliflozin group were decreased in a concentration dependent manner (P<0.05). Additionally, the intracellular and mitochondrial ROS levels were increased, the mitochondrial membrane potential was decreased, and the cytoplasmic mtDNA release level, cGAS-STING pathway-related protein expression and pro-inflammatory factor mRNA levels were increased (all P<0.05). Compared with the canagliflozin group, the intracellular and mitochondrial ROS levels, cytoplasmic mtDNA release levels, cGAS-STING pathway-related protein expression and pro-inflammatory factor mRNA levels in the N-acetyl-L-cysteine (NAC) +canagliflozin group were decreased (all P<0.05). Compared with the canagliflozin group, the proliferation activity and the expression of proliferation-related proteins in the cGAS inhibitor RU.521 + canagliflozin group were significantly increased (all P<0.05).
Canagliflozin induces oxidative stress in liver cancer cells, leading to the accumulation of ROS within cells and mitochondria, impairment of mitochondrial function, leakage of mtDNA into the cytoplasm, activation of the cGAS-STING pathway, and subsequent release of intracellular pro-inflammatory factors. These processes collectively contribute to the modulation of liver cancer cells proliferation.
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Clinically, it manifests as progressive muscle weakness and atrophy, ultimately leading to death, imposing a significant burden on patients’ families and society. The pathogenesis of ALS remains unclear. Currently, several ALS treatment drugs have failed to significantly extend survival or alter the outcome. In recent years, cell therapy has been increasingly applied to refractory or incurable diseases. Various types of stem cell therapies have been developed for ALS treatment, undergoing preclinical research and clinical trials. This article provides an overview of the application of cell therapy in ALS, with a detailed examination of the research and development history of the representative cell therapy NurOwn in ALS. And the achievements and challenges of current ALS cell therapy, suggesting the optimization of cell type selection and efficacy evaluation metrics in future ALS cell therapy research were further discussed. This optimization aims to guide the development, approval, and market entry of ALS cell therapies, benefiting patients and their families.
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