Objective:To explore the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC.(SLEL)on lipopolysac-charide(LPS)-induced acute lung injury(ALI)in rats using metabolomics.Methods:Forty-eight male SD rats were randomly divided into a blank control group(CG),a model control group(MG),low-,medium-,and high-dose SLEL groups(50,100,and 200 mg/kg),and a positive control group(dexamethasone acetate tablets,5 mg/kg).CG and MG groups were given phosphate-buffered saline.All groups received intragastric administration at a dose volume of 10 mL/kg once a day for 7 consecutive days.One hour after the last ad-ministration,LPS(5 mg/kg)was instilled into the trachea of all groups except the CG group to establish the ALI rat model.Twenty-four hours after model establishment,blood was collected from the abdominal aorta and bronchoalveolar lavage fluid(BALF)was col-lected from the left lung.The total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF was counted by Wright-Giemsa staining.The levels of interleukin-18(IL-18)and interferon-γ(IFN-γ)in serum and BALF were measured by enzyme-linked immunosorbent assay.The pathological changes of lung tissue were observed using hematoxylin-eosin staining.The ex-pression levels of tight junction protein-1(ZO-1)and occludin in lung tissue were determined by Western blot.The mRNA expression levels of IL-18,IFN-γ,ZO-1,and occludin in the lung were measured by real-time fluorescence quantitative PCR.Non-targeted me-tabolomics analysis of serum and lung tissue was performed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.Results:Compared with the MG group,all SLEL groups had significantly reduced wet/dry weight ratio of lung tissue,lung coefficient,and total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF.SLEL signifi-cantly decreased the levels of IL-18 and IFN-γ in serum and BALF and the mRNA expression of IL-18 and IFN-γ in lung tissue,and significantly promoted the protein and mRNA expression of ZO-1 and occludin.Under light microscopy,the degree of lung tissue edema,alveolar hemorrhage,and inflammatory cell infiltration were significantly reduced,indicating a certain protective effect on ALI rats.The results of non-targeted metabolomics studies showed that there were 91 and 33 significantly different metabolites in the serum and lung tissue of rats treated with SLEL,respectively.Among them,the main differential metabolites in the serum were sphingosine,L-lactic acid,nicotinic acid,D-nucleotide,and mevalonate-5P,while the main differential metabolites in the lung tissue were tauro-cholic acid.This suggests that SLEL may mainly affect the metabolic pathways of sphingolipids,pyruvate,nicotinic acid,nicotinamide,and tryptophan in the serum and the metabolic pathways of taurine and hypotaurine in the lung tissue to improve ALI.Conclusion:SLEL has a significant protective effect on rats against LPS-induced ALI,and its mechanism of action may be related to the inhibition of inflammatory factors,improvement of lung barrier function,and regulation of related metabolic pathways.

BACKGROUND:Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments.Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis.At present,traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis.Naringin is one of the main active ingredients in Rhizoma Drynariae.Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars,and its clinical and basic research has been gradually emphasized. OBJECTIVE:To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo,thereby providing some ideas for the next step to study its related mechanism of action. METHODS:The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of"naringin,osteoporosis,traditional Chinese medicine compound,pathogenesis,signaling pathway,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English,respectively.The corresponding criteria were established according to the research needs,and finally 69 articles were included for review. RESULTS AND CONCLUSION:Naringin blocks the increase in the number of osteoclasts and adipocytes,the decrease in the number of osteocytes and osteocalcin(+)cells induced by fructose-rich diet,and promotes the secretion of Sema3A from osteoblasts and osteocytes,thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway.Naringin is an important way to induce autophagy of osteoblasts,but autophagy-related proteins participate in osteoblast differentiation and bone formation.Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts,which results in bone loss and decreased bone density.The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties.Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor.Naringin can regulate bone metabolism and inhibit oxidative stress via ERK,PI3K/Akt and Wnt signaling pathways to improve osteoporosis,which can play a good role in preventing and controlling the disease.However,the depth and breadth of the relevant research is insufficient.Based on the mechanism of the current study,we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future,which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis..

Objective:To explore the effect of Annexin A1(ANXA1)peptidomimetic Ac2-26 on acute kidney injury(AKI)and neutrophil apoptosis in septic rats.Methods:Experimental groups included control group,Ac2-26 group,AKI group,AKI+Ac2-26 group,with 15 rats in each group.After cecal ligation and perforation were used to establish a sepsis-induced AKI model,Ac2-26 was intravenously infused for treatment,once a day for 14 days;after the end,ELISA was used to detect levels of serum creatinine(Scr),urea nitrogen(BUN),IL-1β,IL-6 and TNF-α;HE staining and periodic acid Schiff(PAS)staining were used to observe the pathological changes of rat kidney tissues in each group;immunohistochemical staining was used to detect expression of ANXA1 in kidney tissue of each group of rats;neutrophils were isolated from rat peripheral blood,Giemsa staining and trypan blue staining were used to detect cell purity and viability;Annexin V-FITC/PI double staining method and TUNEL staining were used to determine apop-tosis level of neutrophils in each group.Results:Compared with control group,levels of Scr and BUN in serum of rats in AKI group were increased(P<0.05),levels of IL-1β,IL-6 and TNF-α also increased(P<0.05),renal tubules and glomeruli in kidney tissue were both significantly damaged,accompanied by a large number of inflammatory cell infiltration,and pathological score increased(P<0.05),while proportion of ANXA1 positive staining area was decreased(P<0.05);neutrophils identified by Giemsa staining and trypan blue staining had complete morphology and high activity;compared with control group,apoptosis rate of neutrophils in AKI group was decreased(P<0.05),and the positive rate of TUNEL was decreased(P<0.05).Compared with AKI group,levels of Scr and BUN in serum of rats in AKI+Ac2-26 group were decreased(P<0.05),levels of IL-1β,IL-6 and TNF-α also decreased(P<0.05),pathological manifestations of renal tubules and glomeruli in renal tissue were significantly reduced,and pathological score was reduced(P<0.05),while the proportion of ANXA1 positive staining area was increased(P<0.05),at the same time,apoptosis rate of rat neu-trophils was increased(P<0.05),positive rate of TUNEL was also increased(P<0.05).Conclusion:ANXA1 peptidomimetic Ac2-26 can increase expression of ANXA1 in kidney tissue of AKI in septic rats,promote neutrophil apoptosis,and have a protective effect on kidney tissue damage in rats caused by sepsis.

Intestinal injury is a common adverse reaction of clinical chemotherapy drugs, which limits the further application of chemotherapy drugs and causes serious physical and mental burden to patients. At present, the mechanism of chemotherapy-induced intestinal injury is complex, and traditional Chinese medicine has an excellent preventive effect. This article reviews the related mechanisms of intestinal flora imbalance, oxidative stress, inflammatory response, cell apoptosis, and immune damage caused by chemotherapy, and summarizes the role of traditional Chinese medicine in prevention and treatment of oxidative stress, inflammatory response, cell apoptosis, and immune damage.

Objective To observe the myocardial protective effect of dexmedetomidine in patients undergoing open-heart surgery under cardiopulmonary bypass (CPB).Methods 50 patients of open-heart surgery under CPB were randomly divided into two groups equally, namely observation group and control group.Observation group was treated with injection of dexmedetomidine at 0.5 μg/kg for 15 min, and then maintained at 0.4 μg/kgoh.The control group was given equal volume of normal saline.Concentrations of IMA and cTnI were determined before anaesthesia (t0), after 30 minutes of CPB (t1) and after surgery (t2).Results IMA and cTnI concentrations of t1 and t2 in the observation group were significantly lower than those in the control group (P<0.05).Conclusion Dexmedetomidine has obvious protective effect on myocardium, which can reduce open-heart surgery of patients with myocardial ischemia reperfusion injury (MIRI).

Objective This study was to investigate the lymph node metastasis pattern in thoracic esophageal squamous cell carcinoma (ESCC),and analyze the risk factors to provide reference for the delineation of radiotherapy target.Methods A total of 319 patients with thoracic ESCC who underwent surgical treatment at the second hospital of Dalian medical university were analyzed retrospectively.The lymph nodes around esophageal were divided into 20 groups according to the mapping scheme of the American Thoracic Society (ATS) modified by Casson et al.Analyzed the pattern of lymph node metastasis and its relationship with tumor location,tumor length,depth of invasion,pathological grade,and vessel invasion.Results The lymph node metastatic rate was 48.90％ (156/319),while the metastatic ratio of lymph node (LMR) was 15.70％ (562/3 581).The lymph node metastatic rates had gradually increasing trend with tumor sites descending (upper ESCC 35.48％,middle ESCC 47.06％ and lower ESCC 56.43％),but no statistically significance (P ＞ 0.05) was observed.In the whole 20 groups,the higher node metastasis stations of upper thoracic ESCC LMR were 1,2,4,5,7,9 (x2 =27.38,P ＜ 0.05),while the middle thoracic ESCC LMR were 2,4,5,7,8M (x2 =57.77,P ＜ 0.05),and the lower thoracic ESCC LMR were 4,5,7,8L,16,17,20 (x2 =28.88,P ＜ 0.05),with statistically significance.So the main lymph node metastasis stations were paraesophageal nodes,tracheobronchial nodes,paratracheal nodes,aroticopumonary nodes,left gastric nodes,subcarinalnodes and celiac nodes.The univariate analysis revealed that lymph node metastasis was correlated with the tumor length,depth of invasion,pathological grade,and presence of vascular invasion (x2 =6.82,26.04,36.26,4.56respectivcly,P ＜ 0.05).The muhi-variate regression analysis showed that tumor length and depth of tumor invasion were independent risk factors for lymph node metastasis (OR =2.212,2.123,P ＜ 0.05).Conclusions The factors influencing lymph node metastasis in thoracic ESCC include tumor length,depth of invasion,pathological grade,and presence of vascular invasion,which should be carefully considered during the target delineation of radiotherapy for esophageal carcinoma.

OBJECTIVE: To investigate the effect of hypoxia on cell viability and the endothelial differentiation potential in human umbilical cord derived mesenchymal stem cells (UC-MSCs), and to assess the in vitro protective role of VEGF under low oxygen tension. METHODS: MSCs were isolated from human umbilical cords and cultured in vitro. The morphological and phenotypic characterizations of human UC-MSCs were analyzed. The hypoxia induction was performed with or without the presence of 50 ng/mL of VEGF for different lengths of time. The cell proliferation, apoptosis, and reactive oxygen species (ROS) generation were assessed. Meanwhile, the endothelial differentiation potential of the UC-MSCs was measured. RESULTS: An increased apoptosis and ROS generation but reduced proliferation rate were observed at early stages (6, 12 h) after transferring the UC-MSCs from the atmospheric condition to the hypoxia condition. However, the UC-MSCs presented equal proliferation and apoptosis levels under hypoxic condition as compared with those under the atmospheric condition at the later stages (24, 72 h). A high concentration of exogenous VEGF (50 ng/mL) attenuated the increased apoptosis and inhibited the proliferation of UC-MSCs, induced by a short-term hypoxia treatment. After 14 days of exogenous VEGF induction under the hypoxia condition, the UC-MSCs acquired an early endothelial phenotype consisting of a mature endothelial molecule and some endothelial functions. CONCLUSION UC-MSCs progressively adapt to hypoxia in a step-by-step manner and maintain differentiation potential under hypoxia condition. VEGF can protect the UC-MSCs from cell damage and induce a differentiation of UC-MSCs toward endothelial lineage under hypoxic conditions.
Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Hypoxia ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells ; cytology ; Protective Agents ; pharmacology ; Reactive Oxygen Species ; metabolism ; Umbilical Cord ; cytology ; Vascular Endothelial Growth Factor A ; pharmacology

OBJECTIVETo investigate allergic reactions of traditional Chinese medicine (TCM) injections, and to determine the contents of serum IgE and histamine in sensitized animal. The correlation between the preceding contents in serum and allergic reactions may be found, thus offering experimental evidences for advancing the accuracy of anticipation by type I allergy.

METHODWe carried out passive cutaneous anaphylaxis (PCA) tests,active systemic anaphylaxis (ASA) tests and anaphylactoid reactions using three TCM injections, and determined the contents of serum OVA-sIgE, total serum IgE and histamine in sensitized animals by ELISA method.

RESULTThe results of PCA test were negative, and there was no significant difference for total serum IgE level between experimental group and normal saline group. In the study of adjuvant effect in TCM injections + OVA (at the dose level that doesn't cause allergic reactions), the PCA results of SHL and YXC were positive and there was a increase in content of serum OVA-sIgE, while the PCA result of QKL was negative with a unobvious increase in the content of serum OVA-sIgE. The content of total serum IgE wasn't remarkably increased in each group and the results of ASA test were all positive. Three injections all caused anaphylactoid symptoms in guinea pigs in different doses or injection speed and the response intensity was found to be dosage and injection speed dependant. Furthermore, there was no significant difference for the content of total serum IgE in each group, whereas serum histamine concentration in every experimental group was markedly higher than normal saline group.

CONCLUSIONSHL and YXC increase the sensitivity of guinea pigs on OVA, and three TCM injections can cause allergic reactions in guinea pig. Allergic reactions of three TCM injections are correlated with specific IgE antibodies and histamine contents.

Animals ; Female ; Guinea Pigs ; Histamine ; blood ; Hypersensitivity ; drug therapy ; Immunoglobulin E ; blood ; Injections ; Male ; Medicine, Chinese Traditional ; Ovalbumin ; immunology ; Passive Cutaneous Anaphylaxis ; drug effects

Wnt/β-catenin signaling pathway plays an important role in the initiation and progression of colorectal cancer. The key to its carcinogenicity is related to the inhibition of β-catenin degradation, and the subsequent cytoplasmic accumulation and nuclear translocation of β-catenin, which activates the transcription of downstream target genes such as coding region instability determinant-binding protein (CRD-BP). In cancercells ,the expression of CRD-BP mediates the stabilization of β-Trcp, which in normal cells regulates the degradation of β-catenin. The activation of Wnt/β-catenin signaling pathway, overexpression of β-catenin and CRDBP, and the upregulation of β-Trcp by CRD-BP play important roles in the initiation, progression, and metastasis of colorectal cancer.

Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of [Symbol: see text]50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.