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Background: 3-hydroxy-3-methylglutaryl-coenzymOHBe A(HMG-CoA) lyase (HMGCL) catalyzes the cleavage of HMG-CoA into acetyl-CoA and acetoacetic acid and serves as a rate-limiting enzyme in the metabolism of ketone bodies. While HMGCL is involved in various biological processes, its specific role in osteosarcoma remains unclear. Methods: Using data from a public database of osteosarcoma patients, we investigated the expression and prognostic value of HMGCL. The effects of HMGCL on the proliferation, migration, and invasion of osteosarcoma cells were assessed using CCK-8 assays, wound healing tests, and transwell invasion assays. We explored and validated the specific molecular mechanisms by which HMGCL influences osteosarcoma through transcriptome sequencing. Finally, we established a subcutaneous tumor formation model in nude mice to investigate the function of HMGCL in vivo. Results: The expression of HMGCL is downregulated in osteosarcoma and correlates with the prognosis of osteosarcoma patients. Overexpression of HMGCL can inhibit the proliferation, migration, and invasion of osteosarcoma cells, as well as tumor growth in vivo. Through our investigation of the underlying mechanism, we found that HMGCL may inhibit the activation of the PI3K/AKT/mTOR signaling pathway via its product, β-HB. This inhibition promotes the phosphorylation of ULK1, thereby facilitating autophagy in osteosarcoma cells and enhancing the malignancy of the disease. Conclusion: HMGCL inhibits the activation of the PI3K/AKT/mTOR signaling pathway mediated by β-HB, thereby reducing the proliferation, migration, and invasion of osteosarcoma cells while promoting autophagy. HMGCL may represent a new target for the treatment of osteosarcoma, offering new hope for patients with this disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that metformin has anti-inflammatory, anti-tumor, anti-aging and vasoprotective effects, and can inhibit the progression of osteoarthritis, but its specific mechanism of action remains unclear. OBJECTIVE: To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups (n=10 per group): blank, control, sham-operated, and metformin groups. The blank group did not undergo any surgery. In the sham-operated group, the joint cavity was exposed. In the model group and the metformin group, the modified Hulth method was used to establish the osteoarthritis model. At 1 day after modeling, the rats in the metformin group were given 200 mg/kg/d metformin by gavage, and the model, blank, and sham-operated groups were given normal saline by gavage. Administration in each group was given for 4 weeks consecutively. Hematoxylin-eosin staining, toluidine blue staining, and safranin O-fast green staining were used to observe the morphological structure of rat knee joints. Immunohistochemical staining and western blot were used to detect the protein expression of SOX9, type II collagen, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), Beclin1, P62, phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), and p-mTOR in rat cartilage tissue. RESULTS AND CONCLUSION: The results of hematoxylin-eosin, toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group, while in the model group, there was irregular cartilage surface of the knee joint and cartilage damage, with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix. In the metformin group, there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats, and the cartilage surface tended to be smooth, with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix. Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups, the expression of SOX9, type II collagen, and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased (P < 0.05). Conversely, the expression of ADAMTS5, P62, as well as p-PI3K, p-AKT, and p-mTOR proteins was significantly increased (P < 0.05). Furthermore, compared with the model group, the expression of SOX9, type II collagen, and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased (P < 0.05), while the expression of ADAMTS5, P62, as well as p-PI3K, p-AKT, and p-mTOR proteins was significantly decreased (P < 0.05). To conclude, Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/mTOR signaling pathway, thus exerting a protective effect on articular cartilage. [ABSTRACT FROM AUTHOR]

Objective: To investigate effects of macrophage polarization on PI3K/Akt/mTOR signaling pathway and inflammatory response of vascular smooth muscle cells. Methods: THP-1 cells were induced to become macrophages by phaboate, then treated with LPS and IFN-7, IL-4 and IL-13 for 48 h, and cultured with fresh medium without serum for 24 h. Supernatant was used as conditioned medium. Vascular smooth muscle cells were divided into control group, M0 medium group, Ml medium group and M2 medium group. CCK-8 was used to detect cell proliferation, flow cytometry was used to detect cell apoptosis, ELISA was used to detect expressions of inflammatory cytokines IL-la, IL-6 and TGF-β in supernatant of cells, and mRNA and phosphorylated protein expressions of PI3K, Akt and mTOR in vascular smooth muscle cells were detected by RT-qPCR and Western blot. Results: Compared with control group, cell proliferation ability and TGF-β level in supernatant of M0 medium group were significantly decreased (P<0.0l), apoptosis rate, IL-la and IL-6 levels in cell supernatant, mRNA and protein phosphorylation levels of PI3K, Akt and mTOR in cells were significantly increased (P<0.0l). Compared with M0 medium group, cell proliferation ability and TGF-β level in supernatant of Ml medium group were significantly decreased (P<0.05), apoptosis rate, IL-la and IL-6 levels in cell supernatant, mRNA and protein phosphorylation levels of PI3K, Akt and mTOR in cells were significantly increased (P<0.0l), the trend was opposite in M2 medium group (P<0.05). Conclusion: Macrophage polarization can regulate expressions of inflammatory cytokines by regulating PI3K/Akt/mTOR signaling pathway, and participate in inflammatory response in atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is one of the most common cancers in women and poses a serious threat to women's health. Circular RNAs (circRNAs) have been found to be specifically expressed in cancers and regulate the growth and death of tumor cells. The role of circRNAs in breast cancer remain unknown. In this study, we explored the impacts of circRNAs on the progression of breast cancer cells. Methods: Using bioinformatics analysis, we screened out one up-regulated circRNA in breast cancer, and its function and regulatory mechanisms were confirmed by quantitative real-time PCR, cell counting kit-8 experiment, migration assay, dual luciferase reporter assay, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, cell immunofluorescence, clone formation assay, scratch wound healing experiment, RNA immunoprecipitation and subcutaneous tumor-bearing experiments. Results: Circ_0022382 was highly expressed in breast cancer cell lines MDA-MB-231, MCF-7 as well as breast cancer tissues, and promoted the proliferative and migratory capacity of breast cancer cells. In terms of regulatory mechanisms, circ_0022382 activated PI3K/AKT/mTOR signaling pathway and SLC7A11 by sponging let-7a-5p, while knockdown of circ_0022382 contributed to the occurrence of disulfidptosis. In addition, EIF4A3 promoted the expression of circ_0022382 in MDA-MB-231 and MCF-7. Consistently, knockdown of circ_0022382 inhibited the growth of breast cancer cells in vivo. Discussion: Circ_0022382 and its related molecules may be effective targets for diagnosis or targeted therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract G-protein gamma subunit 2 (GNG2) plays a vital role in various cellular processes, yet its specific function in colorectal cancer (CRC), particularly in highly invasive cases and brain metastasis, remains unclear. This study identifies GNG2 as a key regulator in metastatic colorectal cancer (mCRC) through bioinformatics analysis and experimental validation. Functional enrichment analyses reveal that GNG2 is related to the PI3K/AKT/mTOR signaling pathway and cell cycle regulation. These findings were further confirmed by in vitro and in vivo experiments. The overexpression of GNG2 significantly induced G0/G1 arrest and further inhibited the PI3K/AKT/mTOR axis in CRC cell lines, including suppressed proliferation, migration, and invasion and metastasis ability. In vivo studies using an orthotopic xenograft model demonstrated that GNG2 overexpression reduced brain metastasis and extended overall survival in mice. Immunohistochemistry and multiplex immunofluorescence confirmed the association between GNG2 overexpression, the PI3K/AKT/mTOR signaling pathway, and G0/G1 arrest. Our study suggests that GNG2 contributes to tumor suppression in CRC, particularly in preventing brain metastasis, and could serve as a promising biomarker and treatment target for mCRC, offering fresh insights into the molecular processes driving cancer progression and metastasis.

Objective: To investigate the relationship between the expression of serum long non-coding RNA taurine up-regulated gene 1 (LncRNA TUG1) and microRNA-29a-3p (miR-29a-3p) and the degree of lesion, lung function and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/rapamycin target protein (mTOR) signaling pathway in patients with idiopathic pulmonary fibrosis (IPF). Methods: 52 IPF patients (study group) admitted to our hospital from January 2021 to December 2023 were selected, and 50 healthy volunteers (control group) who underwent physical examination in our hospital during the same period were selected. The levels of serum LncRNA TUG1, miR-29a-3p, lung function parameters [total lung capacity (TLC), forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred), forced vital capacity (FVC), carbon monoxide diffusion capacity as a percentage of predicted value (DLCO%pred)], high-resolution computed tomography (HRCT) score and PI3K, Akt and mTOR mRNA expression were com- pared in two groups. The correlation was analyzed by Pearson method. Results: The expression levels of serum LncRNA TUG1, PI3K, Akt and mTOR mRNA in study group were higher than those in control group, and the expression level of miR-29a-3p was lower than that in control group (P<0.05). TLC, FEV,%pred, FVC and DLCO%pred in study group were lower than those in control group, and HRCT score was higher than that in control group (P<0.05). The expression of serum LncRNA TUGI was positively correlated with HRCT score, PI3K, Akt and mTOR mRNA expression, and negatively correlated with TLC, FEV1%pred, FVC and DLCO%pred (P<0. 05). And miR-29a-3p was negatively correlated with HRCT score, PI3K, Akt and mTOR mRNA expression, and positively correlated with TLC, FEV,%pred, FVC and DLCO%pred (P<0.05). Conclusion: Serum LncRNA TUGI is highly expressed, and miR-29a-3p is lowly expressed in IPF patients, the two are closely related to the degree of lung tissue lesions, the degree of lung function damage and the abnormal activation of PI3K/Akt/mTOR signaling pathway in IPF patients [ABSTRACT FROM AUTHOR]

AIM: To explore the possible mechanism of Yiqi-Huoxue formula （YQHXF） in treating cerebral ischemia-reperfusion injury. METHODS: Male SD rats were randomly divided into six groups, namely, the sham, model, nimodipine, and low-, middle- and high-dose YQHXF groups. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established in all groups except the sham group. After successful modeling, the YQHXF low-, medium-, and high-dose groups were given 3. 8, 7. 5, and 15 g∙kg-1∙d-1 of YQHXF, respectively, by gavage, while the nimodipine group was given 12 mg∙kg-1∙d-1 of nimodipine tablets by gavage. The sham and model groups were given 10 mL∙ kg-1∙d-1 of distilled water by gavage. After 14 days of drug intervention, the rats were euthanized and the neurological function was evaluated. The infarct volume was assessed using 2, 3, 5-triphenyltetrazolium chloride （TTC） staining and brain histopathological changes were determined by hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to investigate changes in autophagosomes, with immunofluorescence used to assess expression of microtubule-associated protein 1 light chain 3 （LC3） protein in the cerebral cortex, Western blot was used to measure protein levels of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, mTOR, LC3B, p62, beclin-1, and Atg5, and RT-qPCR was used to determined LC3 and P62 mRNA expression. RESULTS: Compared with the sham group, the neural function scores of rats in the model group rats were significantly increased, and TTC staining revealed large areas of white cerebral infarction. There was severe pathological damage to the cerebral tissue in the ischemic cortical area, and large numbers of autophagosomes were seen inside the cells. Immunofluorescence staining showed significant numbers of LC3B-positive cells （P<0. 01）. Protein expression of beclin-1, Atg5, and LC3-II/LC3-I was significantly upregulated （P<0. 01）, while that of p62 was markedly downregulated （P<0. 01）. The expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR proteins was also significantly reduced （P<0. 01）. In addition, the mRNA expression of LC3 was significantly upregulated （P<0. 01）, with downregulation of P62 mRNA levels （P < 0. 01）. Compared with the model group, both the YQHXF medium- and highdose groups showed upregulated LC3-II/LC3-I values after 12 h of reperfusion （P<0. 01）, followed by downregulation of the ratios （P<0. 05） after 3, 7, and 14 days of reperfusion. Furthermore, after 14 days of reperfusion, compared with the model group, the middle- and high-dose YQHXF groups and the nimodipine group showed reduced neurological function scores（ P<0. 01）, reduced cerebral infarction volumes（ P<0. 01）, improvements in the pathological damage to cortical tissue, and reduced autophagosome formation to varying degrees. At the same time, the number of LC3B-positive cells was reduced （P<0. 01）. Protein expression of beclin-1, Atg5, and LC3-II/LC3-I was significantly downregulated, while that of p62 was upregulated （P<0. 01）. The mRNA expression of LC3 and p62 was consistent with the protein levels （P< 0. 01）. In addition, the expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR proteins was upregulated （P< 0. 01）. CONCLUSION: YQHXF can dynamically regulate autophagy in ischemic brain tissue, with inhibition of excess autophagy by activation of the PI3K/Akt/mTOR signaling pathway, thus reducing the infarct volume, alleviating brain damage, and promoting the recovery of neurological function. [ABSTRACT FROM AUTHOR]

Monocrotaline (MCT), a major pyrrolizidine alkaloid, is well-known for its high liver toxicity. Dysregulation of autophagy induced apoptosis can lead to various liver diseases, including those induced by chemical compounds. Therefore, we aim to explore whether autophagy might serve as a potential strategy for addressing liver apoptosis caused by MCT. In primary rat hepatocytes (PRHs), MCT significantly increased the number of autophagosomes and the expression levels of LC3II, Becline-1, and Atg5, while it decreased the expression of p62 in a concentration-dependent manner at doses of 100, 200, 300, and 400 µM. Western blot assays revealed MCT inhibited the phosphorylation levels of the PI3K/AKT/mTOR pathway. To elucidate the role of autophagy in mediating MCTinduced apoptosis, we further pretreated PRHs with the autophagy agonist Rapamycin and the inhibitors Bafilomycin A1 and Chloroquine, respectively, and assessed the apoptosis of PRHs induced by MCT. The results displayed that Rapamycin increased the apoptosis rate and the expression of cleaved caspase-3, whereas Bafilomycin A1 and Chloroquine reduced the apoptosis and the expression of cleaved caspase-3 in PRHs. This study confirms that autophagy enhances PRHs apoptosis induced by MCT. In summary, this study demonstrates that MCT-induced autophagy via inhibition of the PI3K/AKT/mTOR pathway can lead to apoptosis in PRHs. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by significant hypoxemia, which impairs the oxygen supply necessary for optimal lung function. This study aimed to investigate the effects of sodium propionate (SP), the primary end product of intestinal flora fermentation of dietary fiber, on lipopolysaccharide (LPS)-induced ARDS in rats. The rats were treated with SP, after which the lung wet/dry ratio, arterial partial oxygen pressure (PaO2), levels of pro- and anti-inflammatory cytokines, tight junction proteins ZO-1 and Occludin, as well as LC3 and phosphorylated PI3K (p-PI3K)/p-AKT/p-mTOR protein levels, were measured. Additionally, histopathological analysis was conducted. The results indicated that SP effectively alleviated arterial hypoxemia in rats and mitigated the pathological damage to both intestinal and lung tissues caused by LPS. Notably, SP significantly reduced the levels of inflammatory factors TNF-α and IL-6 in the blood and bronchoalveolar lavage fluid (BALF) of ARDS rats, while increasing the concentration of the anti-inflammatory factor IL-10. Furthermore, SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the LC3II/LC3I ratio in lung tissue. Therefore, SP may improve LPS-induced ARDS in rats by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, promoting autophagy, decreasing the production and release of inflammatory markers, and reducing alveolar epithelial damage. [ABSTRACT FROM AUTHOR]

Objective: To investigate influences of curcumin on LPS-induced autophagy in corneal stromal cells by regulating phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Methods: Mouse corneal stromal cells were grouped into control group, LPS group (1 µg/µl LPS), L-Cur group (15 µmol/L curcumin), M-Cur group (30 µmol/L curcumin), H-Cur group (50 µmol/L curcumin), and H-Cur+740Y-P group (50 µmol/L curcumin+ 10 µmol/L PI3K activator 740Y-P). MTT was applied to detect effect of curcumin on corneal stromal cytotoxicity and cell viability; ELISA was applied to detect levels of inflammatory factors in corneal stromal cells; immunofluorescence staining was applied to detect levels of Beclin1 and LC3 in mouse corneal stromal cells; Western blot was applied to detect expressions of autophagy-related proteins and pathway-related proteins in corneal stromal cells. Results: 0~90 µmol/L curcumin had no obvious toxicity to corneal stromal cells. Compared with control group, A570 nm, levels of Beclin1 and LC3 II/I in LPS group were obviously decreased (P<0.05), levels of IL-6, IL-8, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR were obviously increased (P<0.05); compared with LPS group, A570 nm,, levels of Beclin1 and LC3II/I in L-Cur group, M-Cur group, H-Cur group were obviously increased in turn (P<0.05), levels of IL-6, IL-8, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR were obviously decreased in turn (P<0.05); H-Cur+740Y-P eliminated beneficial effect of curcumin on corneal stromal cells. Conclusion: Curcumin may promote LPS-induced autophagy in corneal stromal cells by down-regulating PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Actin-like protein 8 (ACTL8) significantly correlates with tumor growth and prognosis across various cancer types. Nevertheless, the potential relationship between ACTL8 and gastric cancer (GC) remains uncertain. Objective: This study aimed to elucidate the role of ACTL8 in human GC cells and to explore its mechanism. Methods: Bioinformatics analysis tools, such as GEPIA2, Kaplan–Meier, and STRING, were utilized for a comprehensive investigation of the characteristics and functional roles of ACTL8 in GC, including differential expression, prognostic value, and related signaling pathways. Subsequently, gene expression analyses, cell function assays, and signaling pathway experiments were conducted to verify key findings. Results: Bioinformatics analysis showed that ACTL8 was significantly elevated in GC and closely associated with poor prognosis. Gene expression experiments confirmed the bioinformatics results. Furthermore, ACTL8 knockdown markedly reduced GC cell proliferation and inhibited migration and invasion. Mechanistically, a significant increase in the phosphorylation levels of signaling proteins was observed in GC cells following ACTL8 overexpression, and PI3K/Akt/mTOR pathway inhibitors could reverse this effect. Conclusion: ACTL8 expression is significantly upregulated in GC cells and is closely correlated with poor patient prognosis. Further mechanistic studies revealed that ACTL8 may promote GC cell migration and proliferation through activation of the PI3K/Akt/mTOR signaling pathway. Consequently, ACTL8 emerges as a promising therapeutic target for GC. [ABSTRACT FROM AUTHOR]

The upregulation of programmed death ligand 1 (PD-L1) plays a crucial role in facilitating cancer cells to evade immune surveillance through immunosuppression. However, the precise regulatory mechanisms of PD-L1 in hepatocellular carcinoma (HCC) remain undefined. The correlation between PD-L1 and ubiquitin-like molecules (UBLs) was studied using sequencing data from 20 HCC patients in our center, combined with TCGA data. Specifically, the association between FAT10 and PD-L1 was further validated at both the protein and mRNA levels in HCC tissues from our center. Subsequently, the effect of FAT10 on tumor progression and immune suppression was examined through both in vivo and in vitro experiments. Utilizing sequencing data, qPCR, and Western blotting assays, we confirmed that FAT10 was highly expressed in HCC tissues and positively correlated with PD-L1 expression. Additionally, in vitro experiments demonstrated that the overexpression of FAT10 fostered the proliferation, migration, and invasion of HCC cells. Furthermore, the overexpression of FAT10 in HCC cells led to an increase in PD-L1 expression, resulting in the inhibition of T cell proliferation and the enhancement of HCC cell resistance to T cell-mediated cytotoxicity. Moreover, in vivo experiments utilizing the C57BL/6 mouse model revealed that overexpression of FAT10 effectively suppressed the infiltration of CD8 + GZMB + and CD8 + Ki67 + T cells, as well as reduced serum levels of TNF-α and IFN-γ. Mechanistically, we further identified that FAT10 upregulates PD-L1 expression via activating the PI3K/AKT/mTOR pathway, but not in a ubiquitin-like modification. In conclusion, our findings indicate that FAT10 promotes immune evasion of HCC via upregulating PD-L1 expression, suggesting its potential as a novel target to enhance the efficiency of immunotherapy in HCC. [ABSTRACT FROM AUTHOR]

Backgroud: Rett syndrome is a neurodevelopmental disorder that affects 1 in 10,000 females. Various treatments have been explored; however, no effective treatments have been reported to date, except for trofinetide, a synthetic analog of glycine-proline-glutamic acid, which was approved by the FDA in 2023. Serological biomarkers that correlate with the disease status of RTT are needed to promote early diagnosis and to develop novel agents. Methods: In this study, we performed a high-depth proteomic analysis of extracellular vesicles containing preparations extracted from patient plasma samples to identify novel biomarkers. Results: We identified 33 upregulated and 17 downregulated candidate proteins among a total of 4273 proteins in RTT compared to the healthy controls. Among these, UBE3B was predominantly increased in patients with Rett syndrome and exhibited a strong correlation with the clinical severity score, indicating the severity of the disease. Conclusions: We demonstrated that the proteomics of high-depth extracellular vesicles containing preparations in rare diseases could be valuable in identifying new disease biomarkers and understanding their pathophysiology. [ABSTRACT FROM AUTHOR]

IntroductionBreast cancer is one of the most common cancers in women and poses a serious threat to women's health. Circular RNAs (circRNAs) have been found to be specifically expressed in cancers and regulate the growth and death of tumor cells. The role of circRNAs in breast cancer remain unknown. In this study, we explored the impacts of circRNAs on the progression of breast cancer cells.MethodsUsing bioinformatics analysis, we screened out one up-regulated circRNA in breast cancer, and its function and regulatory mechanisms were confirmed by quantitative real-time PCR, cell counting kit-8 experiment, migration assay, dual luciferase reporter assay, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, cell immunofluorescence, clone formation assay, scratch wound healing experiment, RNA immunoprecipitation and subcutaneous tumor-bearing experiments.ResultsCirc_0022382 was highly expressed in breast cancer cell lines MDA-MB-231, MCF-7 as well as breast cancer tissues, and promoted the proliferative and migratory capacity of breast cancer cells. In terms of regulatory mechanisms, circ_0022382 activated PI3K/AKT/mTOR signaling pathway and SLC7A11 by sponging let-7a-5p, while knockdown of circ_0022382 contributed to the occurrence of disulfidptosis. In addition, EIF4A3 promoted the expression of circ_0022382 in MDA-MB-231 and MCF-7. Consistently, knockdown of circ_0022382 inhibited the growth of breast cancer cells in vivo.DiscussionCirc_0022382 and its related molecules may be effective targets for diagnosis or targeted therapy of breast cancer.

To investigate different irradiation doses of Se-enriched A.Auricularia polysaccharide (SAAP) in type 1 diabetes mellitus (T1DM) mice. In this study, extraction of polysaccharides from selenium-enriched fungus was carried out after 60Co-γ-ray irradiation treatment. The optimal extraction conditions of SAAP were optimized by response surface methodology. The optimal irradiation dose was selected for the study of in vivo hypoglycemia by comparing the hypoglycemic effect of SAAP under different irradiation doses. C57BL/6 T1DM mice model was established by injecting streptozotocin (STZ) to evaluate the effects of fasting blood glucose (FBG), oral glucose tolerance (OGTT), and SAAP on the glucolipid metabolism and the regulation of oxidative stress in T1DM mice. The results showed that after response surface optimization, the optimal extraction conditions for SAAP: Material-liquid ratio of 37.98:1 mL/g, extraction temperature of 97.94 ℃, extraction time of 3.42 h. The optimal parameters were as follows: liquid-material ratio of 38:1 mL/g, extraction temperature 98 ℃, extraction time of 3.5 h, and SAAP concentration of 0.73 mg/mL. SAAP could improve the symptoms of polydipsia, polyphagia and weight loss in T1DM mice (P

Zhen Wang,1,&ast; Hui Xu,1,2,&ast; Zheng Wang,1,&ast; Yu Wang,3,&ast; Jieyao Diao,1 Juntao Chen,1 Yuchen Xie,4 Lijuan Zhang,5 Miaoxiu Li,6 Yanqin Bian,7 Yunfeng Zhou1 1College of Acupuncture and Massage, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Tuina Department, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3College of Computer Science, Xidian University, Xian, People’s Republic of China; 4Tuina Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China; 5Rehabilitation Department, Jiaozuo Coal Industry (Group) Co. Ltd. Central Hospital, Jiaozuo, People’s Republic of China; 6College of Acupuncture and Massage, Shanghai University of Chinese Medicine, Shanghai, People’s Republic of China; 7Orthopaedic Research Laboratory, University of California, Davis, CA, USA&ast;These authors contributed equally to this workCorrespondence: Hui Xu; Yunfeng Zhou, Email 15036065036@163.com; zyf5680198@126.comBackground: Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear.Objective: This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms.Methods: KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings.Results: Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1β, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs.Conclusion: Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.Keywords: knee osteoarthritis, apoptosis, autophagy, tuina, PI3K/AKT/mTOR signaling pathway, in vivo experiment, machine learning

Abstract Background Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI. [ABSTRACT FROM AUTHOR]

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Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of Tiaobu Xinshen Prescription (Codonopsis Radix, Polygoni Multiflori Radix Praeparata, Lycii Fructus, Astragali Radix, etc.) on synaptic plasticity in 5xFAD transgenic mice with Alzheimer’s disease (AD) . Methods Eighteen 5-month-old male wild-type (WT) mice and 18 5xFAD transgenic mice were randomly divided into control group (0.9% NaCl), Tiaobu Xinshen Prescription group (granules, 4.18 g·kg-1 ) and Aricept group (Donepezil Hydrochloride, 0.625 mg·kg-1 ), with six mice in each group. According to the above groups, the rats were given intragastric administration once a day for 60 days. The ultrastructure of hippocampus in mice was observed by transmission electron microscopy. Western Blot was used to detect the protein expression levels of Synaptophsin, PSD-95, p-NMDAR1, NMDAR1, p-CaMKIIa, CaMKIIa, PI3K, p-Akt, Akt, p-mTOR and mTOR in mouse cortical tissue. Results Compared with the WT mice control group, the ultrastructure of synapses in the hippocampal CA1 region of the 5xFAD control group was irregular, the mitochondria was atrophied and reduced, the mitochondrial cristae was broken and disappeared, the synaptic membrane was irregularly and curved, the synaptic vesicles were reduced, and the postsynaptic density (PDS) was thinned or even broken. The protein expressions of Synaptophsin, PSD-95, p-NMDAR1/NMDAR1, p-CaMKIIa/ CaMKIIa, PI3K, p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly down-regulated (P＜0.05). Compared with the mice in the 5xFAD control group, the ultrastructure of synapses in the hippocampal CA1 region of the mice in the Tiaobu Xinshen Prescription 5xFAD group was significantly changed, the number of mitochondria was increased, the number of synaptic vesicles was increased, the synaptic membrane was intact, and the postsynaptic density was thickened. The protein expressions of Synaptophsin, PSD-95, p-NMDAR1/NMDAR1, p-CaMKIIa/CaMKIIa, PI3K, p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly up-regulated (P＜ 0.05). Conclusion Tiaobu Xinshen Prescription may promote the synthesis of synaptic plasticity-related proteins by activating the PI3K/Akt/mTOR pathway, thereby improving the cognitive dysfunction of AD. [ABSTRACT FROM AUTHOR]

Background and Objective: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. Methods: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis‐regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis‐related proteins. Results: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. Conclusion: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis. [ABSTRACT FROM AUTHOR]

Objective To observe the therapeutic effect of inosine on diabetic cognitive impairment (DCI) in rats and to explore its mechanism. Methods SD male rats were randomly divided into the control group, model group, and experimental group, respectively. Rats in the model group and experimental group were treated with high-fat diet combined with the intraperitoneal injection of streptozotocin and were screened out by Morris water maze experiment to obtain the DCI models, except rats in the control group. After successful modeling, rats in the experimental group were intraperitoneally injected with 100 mg/kg inosine, and rats in the control group and the model group were intraperitoneally injected with the same volume of normal saline, once a day, for 4 weeks. Morris water maze test was used to detect the cognitive ability of rats. HE staining was used to observe the morphology of hippocampal neurons. ELISA was used to detect the levels of tumor necrosis factor- α (TNF- α), interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in hippocampus. RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of phosphatidylinositol-3-kinase (PI3K/protein kinaseB (AKT/mammalian target of rapamycin (mTOR) signaling pathway. Results Compared with the control group, the escape latency increased, and the number of crossing the platform decreased in the model group (both P<0. 05). Compared with the model group, the escape latency decreased, and the number of crossing the platform increased in the experimental group (both P<0. 05). In the model group, the hippocampal neurons were loosely arranged and irregularly shaped, and the number was significantly reduced. The hippocampal neurons of the experimental group were relatively neatly arranged and the morphology was regular, and the number increased. Compared with the control group, the levels of TNF-α, IL-1β, IL-6, and MDA in the hippocampus of the model group increased, and the levels of SOD and GSH-Px decreased (all P<0. 05). Compared with the model group, the levels of TNF-α, IL-1β, IL-6, and MDA in the hippocampus of the experimental group decreased, and the levels of SOD and GSH-Px increased (all P<0. 05). The mRNA expression levels of PI3K, AKT, and mTOR and the protein expression levels of PI3K, p-AKT, and p-mTOR were lower in the model group than in the control group (all P< 0. 05). The mRNA expression levels of PI3K, AKT, and mTOR and the protein expression levels of PI3K, p-AKT, and pmTOR in the experimental group were higher than those in the model group (all P<0. 05). Conclusions Inosine can improve the cognition and learning memory in DCI rats, thus alleviating cognitive impairment. The mechanism may be related to activating PI3K/AKT/mTOR signaling pathway and reducing inflammatory response and oxidative stress. [ABSTRACT FROM AUTHOR]

Background and Aim: The role of C6ORF120 in promoting CCL4‐induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120−/−) and LX‐2 cells (a type of human hepatic stellate cell line). Methods: In vivo experiments, wild‐type and C6orf120−/− rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX‐2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis‐associated factors. Results: C6orf120−/− rats showed mild fibrosis and liver injury in the CCL4‐induced liver fibrosis model. Furthermore, RNA‐seq revealed that C6orf120−/− rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX‐2 cell activation. Moreover, mechanistic studies revealed that the p‐PI3K/PI3K, p‐Akt/Akt, and p‐mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX‐2 cells. Conclusion: C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Heart failure is a syndrome of impaired cardiac circulation caused by the inability of the heart to provide adequate blood supply. Objective: This study aimed to evaluate the improvement of ventricular remodeling and the regulation of PI3K/Akt/mTOR signaling pathway in rats with heart failure by polysaccharides from Stropharia rugosoannulata. Results: In high dose group of polysaccharides from Stropharia rugosoannulata, the levels of LVESD, LVEDD, LVMI, CI, PVCA, CVF, and MMP-2 and MMP-9 mRNA expression in rats with heart failure were significantly decreased, while the levels of LVEF, LVFS were significantly elevated (P<0.05). In high dose group of polysaccharides from Stropharia rugosoannulata, the levels of PI3K, p-Akt/Akt, p-mTOR/mTOR, and cleaved-caspase 3 expression and TIMP-1 mRNA expression were significantly elevated, while Bax, p65, Bcl2 protein expression and serum levels of PRA, AngII, ALD, IL-6, TNF-α, ST2 and NT-proBNP were significantly decreased (P<0.05). Conclusions: Polysaccharides from Stropharia rugosoannulata can improve ventricular remodeling and cardiac function, reduce inflammatory response and protect cardiac function in rats with heart failure in a dose-dependent manner, and the mechanism of action may be related to the regulation of MMPs/TIMPs balance, inhibition of RAAS system and activation of PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of isoliensinine (Iso) on the proliferation, apoptosis and autophagy of colon cancer SW480 cells through PI3K/Akt/mTOR signaling pathway. Methods: Colon cancer SW480 cells were treated with 10, 20 and 40 μmol/L Iso, and the effects of Iso on the cell proliferation capacity, apoptosis and expressions of autophagy related proteins LC3 I, LC3II and p62 were detected by CCK-8, flow cytometry and Western blot, respectively. Then, SW480 cells were treated respectively with 20 μmol/L Iso and 25 μmol/L PI3K activator 740 Y-P, and the cells were divided into the control group, the 740 Y-P group, the Iso group and the Iso+740 Y-P group. The effects of 740 Y-P on the apoptosis and the expressions of LC3 I, LC3 II, p62, PI3K, p-PI3K, mTOR and p-mTOR proteins in each group were detected by flow cytometry and WB. Results: After treatments with 10, 20 and 40 μmol/L Iso, the proliferation capacity of SW480 cells was decreased significantly (all P<0.05); the apoptosis rate was increased significantly (all P<0.05); the expressions of LC3 II/LC3 I were up-regulated significantly (all P<0.05), and the expression of p26 protein was down-regulated significantly (all P<0.05). After treatments with Iso and 740 Y-P, compared with the control group, the apoptosis rate and LC3 II/LC3 I expression of the 740 Y-P group were decreased significantly (both P<0.05), while the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were increased significantly (all P<0.05).The apoptosis rate and LC3 II/LC3 expression in the Iso group were increased (both P<0.05) and the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were decreased (all P<0.05). Compared with the 740 Y-P group, the apoptosis rate and LC3 II/LC3 I expression were increased in the Iso+740 Y-P group (P<0.05), while the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were decreased (all P<0.05). Compared with the Iso group, the apoptosis rate and LC3 II/LC3 I expression were decreased (both P<0.05), and the expressions of p26, p-PI3K/PI3K, and p-mTOR/mTOR were increased significantly (all P<0.05) in the Iso+740 Y-P group. Conclusion: Iso inhibits the proliferation and induces the apoptosis and autophagy of SW480 cells by inhibiting PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

This study focused on examining the effects and mechanism of action of ginseng flower alcohol extract (GFAE) on a drug-induced liver injury (DILI) mice model. Ginseng blossoms were extracted with alcohol and examined for their principal active components using high performance liquid chromatography (HPLC), revealing that GFAE was made up of six ginsenoside active components. By creating a mouse model of DILI and measuring its relevant inflammatory indexes and related proteins, it was revealed that GFAE treats DILI by decreasing inflammatory factors, inhibiting inflammation and hepatocyte apoptosis, suppressing abnormal activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Rapamycin Target Protein (PI3K/AKT/mTOR) signaling pathway, and increasing beneficial bacteria in the intestinal tract, enhancing intestinal flora diversity, and improving the intestinal environment.

Objective: To investigate the efficacy and mechanism of Qili Qiangxin capsule combined with rosuvastatin in the treatment of coronary heart disease based on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Methods: 113 patients with coronary heart disease were divided into control group (n=56) and study group (n=57) by envelope drawing method. The control group was treated with rosuvastatin on the basis of routine treatment, and the study group was treated with Qili Qiangxin capsule on the basis of the control group. The efficacy, vascular endothelial function, inflammatory factors, oxidative stress indexes, PI3K/AKT/mTOR signaling pathway related indexes and incidence of adverse reactions were compared between two groups. Results: The total clinical effective rate in study group was higher than that in control group (P<0.05). The levels of interleukin-6 (IL-6), PI3K messenger ribonucleic acid (mRNA), endothelin-1 (ET-1), AKT mRNA, tumor necrosis factor-a (TNF-a), monocyte chemoattractant protein-1 (MCP-1), mTOR mRNA, malondialdehyde (MDA)in study group were lower than those in the control group, and nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were higher than those in control group after treatment (P<0.05). There was no difference in the total incidence of adverse reactions between the two groups(P>0.05). Conclusion: Qili Qiangxin capsule combined with rosuvastatin is effective in the treatment of coronary heart disease, which can improve vascular endothelial function, inhibit inflammatory response and oxidative stress, its mechanism may be related to the regulation of PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin (ISL) is a chalcone that has shown great potential in the treatment of cancer. However, its relatively weak activity and low water solubility limit its clinical application. In this study, we designed and synthesized 21 amino acid ester derivatives of ISL and characterized the compounds using 1H NMR and 13C NMR. Among them, compound 9 (IC50 = 14.36 μM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC50 = 126.5 μM), and it was superior to the positive drug 5-FU (IC50 = 33.59 μM). The mechanism of the action experiment showed that compound 9 could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]