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Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P<0.05,P<0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P<0.05,P<0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P<0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P<0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P<0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.
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Objective:This study aimed to compare the dosimetric differences in unintended irradiation to the ipsilateral axillary region between intensity-modulated radiation therapy(IMRT)and intensity-modulated proton therapy(IMPT)in patients receiving whole breast irradiation(WBI). Methods:A total of 20 patients with early breast cancer who received WBI at our center between August and September 2022 were included in this study.One IMPT plan and one IMRT plan were formulated for each patient,with prescription dose of 4005 cGy(RBE)in 1 5 fractions.Dosimetric parameters of axillary lymph nodes(ALN)level Ⅰ,Ⅱ,Ⅲ,Rotter's lymph nodes(RN),and the axillary-lateral thoracic vascular junction(ALTJ)were compared between IMPT and IMRT plans. Results:All plans met the criteria of CTV V95%Dose≥95%.IMPT showed significantly better conformity index(0.97 vs 0.95,P=0.0003)and homogeneity index(0.05 vs 0.07,P=0.0301)compared to IMRT.The mean dose of the heart[27.48 vs 114.74 cGy(RBE),P<0.0001]and ipsilateral lung[356.66 vs 498.89 cGy(RBE),P<0.0001]were significantly lower in the IMPT plan compared to the IMRT plan.The mean dose,V50%Dose,V80%Dose,V90%Dose,and V95%Dose of ALNⅠ,ALN Ⅱ,ALN Ⅲ and RN in the IMPT plan were significantly lower than those in the IMRT plan(all P<0.01),with the most significant difference observed in the dosimetric parameters of the axillary region inferior to the axillary vein[mean dose:79.75 vs 995.31 cGy(RBE),P<0.0001].The mean dose and serial dosimetric parameters(V5,V10,V15,V20,V25,V30,and V35)of the ALTJ were also significantly lower in IMPT plans compared to IMRT plans. Conclusion:IMPT demonstrates lower unintended irradiation dose in the inferior axillary region and reduces dose volume in the ALTJ region compared to IMRT.When employing IMPT,the clinical target volume(CTV)should be delineated based on the individual locoregional recurrence risk for patients with positive sentinel lymph nodes who omitted axillary lymph node dissection.For high-risk patients,the axillary region should be included in the CTV to ensure efficacy,while for low-risk patients,excluding the axillary region can help mitigate the risk of breast cancer-related lymphedema.
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Breast cancer-related lymphedema(BCRL)is one of the most common complications after multidiscipline treatment of breast cancer,which manifests as upper limb swelling and skin changes and significantly affects limb function and quality of life.The occurrence and development of BCRL are affected by many factors including surgery,radiotherapy,drugs,infection,trauma,and so on.Therefore,it is important to identify the potential risk factors to establish individualized prevention strategies.Evidence-based risk assessment models for BCRL could help clinicians to identify high-risk patients and apply prospective surveillance to treat BCRL at early stage.For patients with advanced lymphedema,conservative treatment and surgical treatment could be delivered to relieve symptoms and improve their conditions.This article comprehensively reviewed the risk factors,prospective surveillance,intervention,and research progress of BCRL,to provide reference for multidisciplinary collaboration as well as clinical diagnosis and treatment in this field.
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OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.
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Circadian rhythm is driven by the suprachiasmatic nucleus biological clock, and many life activities and physiological functions are regulated by circadian rhythm, such as central nervous system activity, autonomic nervous system activity, endocrine function, metabolism and immune function. At the molecular level, circadian rhythm is regulated by molecular mechanisms generated by clock genes′ oscillations. Endogenous circadian rhythm is one of the main processes controlling sleep. Circadian rhythm disorder is the most common cause of abnormal sleep-wake cycle, and can also lead to a series of diseases and adverse consequences such as other sleep disorders, abnormal cognitive function, hypertension, diabetes and tumors. Recently, the relationship between circadian rhythm and sleeping awakening has become a hot topic for researchers. In this paper, the research progress of circadian rhythm and circadian rhythm sleep-wake disorders was reviewed.
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Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.
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Cytoskeletal Proteins , Endothelial Cells , Extracellular Traps , Integrins , Intercellular Adhesion Molecule-1 , Lipopolysaccharides/pharmacology , Macrophages , NeutrophilsABSTRACT
OBJECTIVE@#To study the effects of high-fat (HF) diet and exercise on the expressions of asprosin and CTRP6 in adipose tissues in different regions of rats during mid-gestation.@*METHODS@#Pregnant SD rats were fed on a standard chow diet or a high-fat (60% fat content) diet for 14 days starting on gestation day (GD) 1. Starting from GD3, the rats fed either on normal or high-fat diet in the exercise groups (CH-RW and HF-RW groups) were allowed access to the running wheels for voluntary running, and those in sedentary groups (CH-SD and HF-SD groups) remained sedentary. At the end of the 14 days, adipose tissues were sampled from different regions of the rats for detecting the mRNA and protein expressions of asprosin and CTRP6 using RT-qPCR and Western blotting.@*RESULTS@#The mRNA expression of asprosin in retroperitoneal adipose tissues was significantly higher in HF-RW group than in the other 3 groups (@*CONCLUSIONS@#High-fat diet and exercise during mid-gedtation can affect the expression levels of asprosin and CTRP6 in adipose tissues of rats in a site-specific manner.
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Animals , Female , Pregnancy , Rats , Adipokines , Blood Glucose , Diet, High-Fat/adverse effects , Intra-Abdominal Fat , Rats, Sprague-DawleyABSTRACT
Objective:To explore the risk factors of acute kidney injury(AKI) in patients after radical nephrectomy.Methods:We retrospectively collected clinical information of 920 patients with renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University from February 2013 to September 2017. There were 612 male and 308 female patients included in this study, with a median age of 60 (range from 20-75 years). 313 patients (34.0%) had hypertension, 132 patients (14.3%) had diabetes, and 111 patients (12.1%) had smoking history. 829 cases (90.1%) were in stage 1-2 for preoperative renal function staging, and 91 cases (9.9%) were in stage 3-5. Preoperative hemoglobin was lower than the lower limit of normal in 391 cases (42.5%), white blood cell count increased in 66 cases (7.2%), and platelet increased in 72 cases (7.8%). Albumin was lower than the lower limit of normal in 65 cases (7.1%), lactate dehydrogenase increased in 73 cases (7.9%). blood urea nitrogen increased in 48 cases (5.2%), uric acid increased in 123 cases (13.4%), and urinary protein was positive in 88 cases (9.7%). 496 cases (53.9%) underwent open surgery and 424 (46.1%) underwent laparoscopic surgery. The changes in serum creatinine were followed up within 48 hours after surgery. AKI was defined according to the KDIGO standard. Logistic regression was used to analyze the risk factors for postoperative stage 2-3 AKI in patients.Results:Stage 1-3 AKI occurred on 627, 42 and 10 patients during hospitalization, respectively. Univariate analysis showed that diabetes ( OR=2.34, P=0.01), positive urine protein ( OR=2.22, P=0.04), and elevated white blood cell count ( OR=2.54, P=0.02) were significantly associated with postoperative stage 2-3 AKI. Multivariate logistic regression analysis showed that diabetes ( OR=2.51, P=0.01) and elevated white blood cell count ( OR=2.69, P=0.02) were independent risk factors for postoperative stage 2-3 AKI. Conclusion:Renal cell carcinoma patients with diabetes or preoperative elevated white blood cell count are more likely to develop stage 2-3 AKI after radical nephrectomy.
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To characterize the timeliness of β3 adrenergic receptor agonist CL316,243-induced browning of white adipose tissues in mice. Methods: Male C57BL/6J mice at 10 weeks of age were housed in conventional cages and given sterile saline for the control group or CL316,243 (1 μg/g) for the experimental group via intraperitoneal injection for 1, 3, and 5 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous white adipose (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological and gene expression analysis. Results: Compared with the control group, intraperitoneal injection of CL316,243 reduced the weight of eWAT on the first day. Meanwhile, CL316,243 continuously promoted the mRNA and protein expression of uncoupling protein-1 (UCP-1) in sWAT and eWAT. Furthermore, CL316,243 injection significantly decreased the food intake and weight gain of the mice, and reduced the diameter of adipocyte and accumulation of small lipid droplets in adipose tissues. Conclusion: CL316,243 can induce the brown-like remodeling in adipose tissues of mice in vivo, which show different time-dependent manners in different adipose tissues.
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Animals , Male , Mice , Adipose Tissue, Brown , Adipose Tissue, White , Adrenergic beta-Agonists , Mice, Inbred C57BL , Uncoupling Protein 1ABSTRACT
In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers. .
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Animals , Humans , Antineoplastic Agents, Immunological , Therapeutic Uses , B7-H1 Antigen , Genetics , Allergy and Immunology , Immunotherapy , Lung Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , Programmed Cell Death 1 Receptor , Genetics , MetabolismABSTRACT
OBJECTIVE@#To investigate the time-sequential expression of a novel long non-coding RNA, lnc AK079912, in metabolically related tissues and during adipose tissue development and browning in mice.@*METHODS@#The interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), epididymal white adipose tissue (eWAT), liver tissues and muscular tissues were collected from 8-week-old C57BL/6J mice. The iBAT, sWAT and eWAT were also collected from the mice during development (0 day, 21 days, 8 weeks and 6 months after birth) and from 8- to 10-week- mice with cold exposure (4 ℃) and intraperitoneal injections of CL316, 243 (1 μg/g body weight) for 1 to 5 days. Trizol was used to extract the total RNA from the tissues, and RT-qPCR was performed to detect the expressions of lnc AK079912. Isolated mouse preadipocytes in primary culture were induced for adipogenic differentiation for 9 days and then treated with CL316, 243 (2 μmol/L) for different durations (no longer than 24 h); the expression of lnc AK079912 in the cells was detected using RT-qPCR at different time points of the treatment.@*RESULTS@#Lnc AK079912 was highly expressed in mouse adipose tissues, the highest in iBAT, followed by the muscular tissue, but was hardly detected in the liver tissue. The expression level of lnc AK079912 increased progressively in iBAT and sWAT during development of the mice, while its expression in eWAT showed an initial increase followed by a reduction at 8 weeks ( 0.05). The expression of lnc AK079912 was significantly decreased in iBAT and eWAT ( < 0.05) but increased in eWAT from mice with intraperitoneal injection of CL316, 243 for 1 to 5 days ( < 0.05). The expression level in the adipocytes in primary culture was significantly increased in response to treatment with CL316, 243 ( < 0.05).@*CONCLUSIONS@#Lnc AK079912 is highly expressed in mouse adipose tissue, and its expression gradually increases with the development of adipose tissue but with a depot-specific difference. Lnc AK079912 is significantly elevated in the early stage of adipose tissue browning, indicating its important role in the development and browning of adipose tissue.
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Animals , Male , Mice , Adipocytes , Adipogenesis , Adipose Tissue, Brown , Adipose Tissue, White , Mice, Inbred C57BL , RNA, Long NoncodingABSTRACT
Some kinetic characteristics of beta-adrenoceptor on circulating intact lymphocytes (CIL) in the combined renovasoeular hypertensive and diabetic (HD) rats were studied and the relation of betareceptos between CIL and cardium as well as the morphologic changes in the processe of dilated cardiomypathy (DCM) were observed. The results show that: the density of beta-adrenoceptor on CIL (Bmax) was going up 41.28%(P0.05), but the Kd was still 50.01%(P