Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral tech-niques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

Objective: To discuss the clinical application and effects of domestic external fixator in the treatment of patients with malformations of limbs. Methods: A total of 7 289 patients with malformation of limbs who had been operated in Qin Sihe orthopedic surgery team from January 1989 to June 2016 were retrospective analyzed. The patients were treated with domestic external fixator, including 4 033 males and 3 256 females, aging from 2 to 82 years with a mean age of 23.4 years. There were 2 732 patients using Ilizarov external fixator, 4 713 patients using hybrid external fixator, 57 patients using monobrachial external fixator, 232 patients using Ilizarov external fixator and hybrid external fixator. The Ilizarov, hybrid and monobrachial external fixator were used in 67, 65 and 0 patients on the upper limbs and in 2 665, 4 616 and 57 patients on the lower limbs. There were 3 028 patients operated on the left limbs, 3 260 patients operated on the right limbs and 1 001 patients operated on the bilateral limbs. The top three types of diseases were sequelae of poliomyelitis, cerebral palsy and post-traumatic stress disorder peromely. Deformity types inclued talipes equinovarus, knee flexion deformity, cavus foot and so on. Results: All the patients were followed up for a period of 2.5 months to 22.4 years, with an average follow-up time of 5.4 years. All of the external fixators were used for single once, and there was no substitute for external fixator quality problem. All the patients were completed surgery goal until removing external fixation except 1 patient gave up treatment and 1 removed the fixator because of metal allergy. The common complications included wire or pin infection and joint movement limitation and so on. Conclusions The domestic external fixator developed and produced based on the characteristics of Chinese limb deformity disability. The domestic external fixator can be used to treat kinds of limb deformities with the advantages of practical, economical, adjustable, universal and portable. The domestic external fixator could meet the clinical demand for fixation of the osteotomy end of the limbs, the correction of the deformity, the repair of the defects and the limb lengthening.

The single nucleotide polymorphisms (SNP) of vitamin D receptor (VDR) gene were determined by BsmI restriction endonuclease analysis and quantitative ultrasonography indexes (QUI) of calcaneum were measured in Tibetan women. The results showed that there were no statistical differences between QUI of different genetypes and between distribution frequencies of gene types in young women and menopausal women. And it was found that the SNP of VDR by BsmI restriction endonuclease analysis was not relevant to bone mass acquisition and rate of bone mass loss.

Object To study the effect of Haimidin(HMD) on erythrocyte membrane of H 22 ascites tumor bearing mice and DNA synthesis in human gastric tumor cell Methods By fluorescence spectrophotometry and laser scanning confocal microscopy Results HMD can lower erythrocyte microviscosity and elevate membrane lipid fluidity of H 22 ascite tumor bearing mice It also reduced DNA fluorescent intensity and DNA content of gastric tumor cells in vitro Conclusion HMD can improve blood circulation of tumor bearing mice, enhance immune adherence of erythrocyte on tumor cells and displays its antitumor activity by interferring DNA synthesis of tumor cells

Aim To investigate the direct effects and mechanism of carvedilol on HERG channel stably expressing in human embryonic kidney-293(HEK293) cells.Methods Whole-cell patch-clamp technique was used to record HERG current and kinetic curves in single cells.Western blot methods were used to investigate the expression of HERG channel in different concentration of carvedilol.Result Carvedilol decreased HERG current in a concentration-dependent manner with an IC50 539.6 nmol?L-1,Hillslope-0.64.The time constants of onset of inactivation and deactivation were accelerated.Other kinetcs(activation,inactivation,recovery from inactivation)had no significant changes.Based on western result,carvedilol had no effect on the generation and trafficking of HERG protein.Conclusion Carvedilol inhibits the transfected HERG channels by influencing the open state which is the probable anti-arrhythmic mechanism.There is no relationship between carvedilol and HERG channel expression.

Immunoenhancement activity of bee pollen and its acetone extract was studied in normal, sarcoma-180 bearing, cyclophosphamide- and antilymphocyte serum-treated mice.Bee pollen and its acetone extract given orally for 30 days could significantly increase the production of serum anti-SRBC hemolysin (HC50) and the number of spleen plaque forming cells (PFC) in primary response to sheep red blood cell (SRBC) in young and adult mice. The acetone extract of bee pollen could significantly prevent the decrease of HC50) the number of PFC and specific rosette forming cells (SRFC), and the quantitative hemolysin of spleen cells (QHS) against SRBC in S-180 bearing, cyclophosphamide- and antilymphocyte serum-treated mice respectively.These results suggested that bee pollen of Brassica campestris L. and its acetone extract have immune-enhancement activity.

The effect of bee pollen of Brassica campestris L. and its alcohol extract on lipid peroxidation was observed in vivo and in vitro.The results showed that the production of lipid peroxides in normal liver hotnogenate of mice and elevation of production of lipid peroxides induced by cysteine and FeSO4 in homogenate were found to be inhibited significantly by in vitro addition of alcohol extract of bee pollen.The elevation of lipid peroxides in serum and liver in adult mice induced by alloxan 75 mg/kg(iv)or by administration of peroxidized corn oil 0.2 ml/mouse was markedly inhibited by oral administration of bee pollen (10 g? kg-1?d-1)for 20 days as compared with respective control groups.The level of lipid peroxide in geriatric mice was also markedly lowered by oral administration of bee pollen (10 g?kg-1?d-1)for 3 months as compared to non-treated geriatric mice.Based on the above in vitro and in vivo experimental results, it may be suggested that bee pollen and its alcohol extract protect tissues against destruction by lipid peroxides.