OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To explore the effects of different education and examination methods on the examination results during the screening/evaluation of patent foramen ovale by contrast-enhanced transcranial Doppler(cTCD).Methods Patients who underwent cTCD screening/evaluation for patent foramen ovale in our hospital from May 2023 to February 2024 were retrospectively selected as the research subjects.The patients were divided into the observation group and the control group according to different education and examination methods during the peri-examination period.Patients who received video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe were included into the observation group,and patients who received artificial education,Valsalva maneuver,and injection of contrast agent with 10 mL syringe were included into the control group.The positive detection rate of patent foramen ovale,right-to-left shunt microbubble grading during Valsalva/modified Valsalva maneuver,systolic blood flow velocity,pulsatility index(PI),resistive index(RI),examination duration,total physician-patient communication time,whether occlusion surgery was performed,and patient satisfaction were compared between the two groups.Results The positive detection rate of patent foramen ovale by cTCD(82.93%vs.95.92%),the detection rate of the maximum amout(grade Ⅲ)of microbubbles(39.02%vs.61.22%),the total physician-patient communication time during the peri-examination period[11.30(10.00,14.00)minutes vs.8.23(7.00,10.00)minutes],the rate of occlusion surgery(48.78%vs.73.47%),and the total patient satisfaction(80.49%vs.91.84%)showed statistically significant differences between the control group and the observation group(P<0.05).Additionally,the receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)for diagnosing patent foramen ovale were 0.718 in the control group and 0.855 in the observation group.Conclusion Peri-examination interventions such as video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe can improve the positive detection rate of patent foramen ovale,reduce ineffective physician-patient communication,and improve patient satisfaction.

Objective To explore the effects of different education and examination methods on the examination results during the screening/evaluation of patent foramen ovale by contrast-enhanced transcranial Doppler(cTCD).Methods Patients who underwent cTCD screening/evaluation for patent foramen ovale in our hospital from May 2023 to February 2024 were retrospectively selected as the research subjects.The patients were divided into the observation group and the control group according to different education and examination methods during the peri-examination period.Patients who received video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe were included into the observation group,and patients who received artificial education,Valsalva maneuver,and injection of contrast agent with 10 mL syringe were included into the control group.The positive detection rate of patent foramen ovale,right-to-left shunt microbubble grading during Valsalva/modified Valsalva maneuver,systolic blood flow velocity,pulsatility index(PI),resistive index(RI),examination duration,total physician-patient communication time,whether occlusion surgery was performed,and patient satisfaction were compared between the two groups.Results The positive detection rate of patent foramen ovale by cTCD(82.93%vs.95.92%),the detection rate of the maximum amout(grade Ⅲ)of microbubbles(39.02%vs.61.22%),the total physician-patient communication time during the peri-examination period[11.30(10.00,14.00)minutes vs.8.23(7.00,10.00)minutes],the rate of occlusion surgery(48.78%vs.73.47%),and the total patient satisfaction(80.49%vs.91.84%)showed statistically significant differences between the control group and the observation group(P<0.05).Additionally,the receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)for diagnosing patent foramen ovale were 0.718 in the control group and 0.855 in the observation group.Conclusion Peri-examination interventions such as video education,modified Valsalva maneuver,and injection of contrast agent with 20 mL syringe can improve the positive detection rate of patent foramen ovale,reduce ineffective physician-patient communication,and improve patient satisfaction.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Chronic pelvic inflammatory disease(CPID)is a common chronic inflammatory disease in women,and has a long course and is easy to relapse.Danggui Shaoyao Powder is from Jin Gui Yao Lve(Synopsis of the Golden Chamber),which was a commonly-used formula for the treatment of women's abdominal pain in ancient medical records.It is now often used in the treatment of CPID and has achieved satisfactory therapeutic effect.The article summarizes and analyzes the achievements in the clinical research and experimental study of Danggui Shaoyao Powder in the treatment of CPID over the past 10 years,and invesigates the clinical efficacy of Danggui Shaoyao Powder in the treatment of CPID and its therapeutic mechanism.In the field of clinical studies,Danggui Shaoyao Powder for the treatment of CPID was used by modification,or alone,or in combination with antibiotics and Chinese medicine external treatment,and its combined use was effective on significantly improving the indicators of inflammatory response and immune function,alleviating the clinical signs and symptoms such as pain,and did not increase the incidence of adverse reactions compared with the application of western medicines alone.In the field of experimental studies,Danggui Shaoyao Powder played the therapeutic role in CPID by decreasing the adhesion of endothelial cells,regulating the degradation of extracellular matrix,improving the level of inflammatory factors,and down-regulating the expression of proteins related to the nuclear factor κB(NF-κB)pathway.

An electrochemical chemical oxygen demand(COD)sensor was proposed based on a FTO/TiO2/PbO2 electrode and a thin-layer electrochemical cell.The FTO/TiO2/PbO2 electrode was characterized by X-ray photoelectronic spectroscopy(XPS),X-ray diffraction(XRD)spectroscopy and electrochemical technique,and the results indicated that the rapid decrease in the output signals of the electrochemical COD sensor could be attributed to oxidation of PbSO4 occurring on the surface of FTO/TiO2/PbO2 electrode.The PbO2 deposition time and concentration of Na2SO4 were further optimized and then the electrochemical COD sensor was challenged by real samples including laker water sample,river water sample and wastewater sample.The evolution trend of signals of the electrochemical COD sensor in response to lake and river water samples was identical with that obtained with the standard method(HJ/T399-2007,Water quality-determination of the chemical oxygen demand-fast digestion-spectrophotometric method).The electrochemical COD sensor exhibited significant increase in the signal intensity after the samples were switched from lake water to wastewater sample,and a mean value of 32.5 mg/L with relative standard deviation(RSD)of 6.8%were obtained after measuring 45 times the wastewater with COD value of 30 mg/L under a sampling interval of 400 s.The as-prepared electrochemical COD sensor possessed good promise in regular monitoring of COD,discharge of wastewater and industrial process control,with advantages such as a small sampling interval,mild reaction conditions and no requirement of toxic and harmful chemical reagents.