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Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.
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Pharmaceutical Preparations , Peptides/chemistry , Amino Acid Sequence , Nanostructures/chemistry , Drug Delivery SystemsABSTRACT
Objective To evaluate the analgesic effect of tetrodotoxin (TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine (1 mg/kg) or TTX (0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models. TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase I and phase II, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid. Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin, but limited analgesic effect was observed on the physical stimulation pain model induced by heat (hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.
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Portopulmonary hypertension (POPH) is an increase in pulmonary artery pressure that occurs on the basis of portal hypertension. As a member of the BMP family, bone morphogenetic protein 9 (BMP9) not only has the osteogenic activity, but can also protect endothelial integrity and maintain vascular homeostasis. This article reviews the pathogenesis of POPH, the physiological expression and role of BMP9, and related research advances in the BMP9 signaling pathway and its involvement in pulmonary hypertension and vascular remodeling, thereby exploring the possibility of BMP9 as a new biomarker for POPH to assist in the diagnosis of POPH.
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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age, with the clinical manifestations of oligomenorrhea or amenorrhea, hyperandrogenism, and anovulatory infertility, and it is often accompanied by metabolic disorders such as obesity, insulin resistance, hyperinsulinemia, and glucose and lipid metabolism disorders. Women with PCOS often have nonalcoholic fatty liver disease (NAFLD) and other metabolic-associated diseases, and PCOS and NAFLD are related in terms of pathogenesis and treatment. This article reviews the research advances in PCOS with NAFLD in recent years.
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ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus （T2DM）-induced cognitive impairment （DCI） and explore the pathway in the prevention and treatment of DCI. MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin （STZ） combined with the high-fat and high-sugar diet （STZ）. The model rats were divided into model group， metformin group （200 mg·kg-1）， and low-，medium-， and high-dose Yuyetang groups（4.575，9.15， 18.3 g·kg-1）according to the blood glucose， with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days， and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention， the learning and memory abilities of rats were tested by the Morris water maze. After the test， the whole brains of rats were sampled for hematoxylin-eosin （HE） staining to observe the pathological changes in the hippocampal CA1 region， and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry. ResultCompared with the normal group ， the model group showed increased blood glucose（P<0.01），reduced body weight（P<0.01），prolonged escape latency（P<0.05，P<0.01）， shortened retention time and movement distance in the target area，decreased number of platform crossings（P<0.01）， abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region， and decreased expression of Ghrelin in the serum，hippocampal CA1 region， and gastric tissues（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Yuyetang groups showed increased body weight， while all Yuyetang groups showed reduced blood glucose（P<0.01）， shortened escape latency （P<0.05）， prolonged retention time and movement distance in the target area，increased platform crossings （P<0.05， P<0.01）， improved morphology and structure of cells， increased number of normal cell in the hippocampal CA1 region， and elevated Ghrelin levels in the serum， gastric tissues， and hippocampal CA1 region（P<0.05， P<0.01）. ConclusionYuyetang can effectively improve the cognitive ability of DCI rats， and its mechanism may be related to the regulation of Ghrelin levels in the serum， hippocampal CA1 region， and gastric tissues.
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Objective:To investigate the phagocytosis of Treponema pallidum (Tp) by macrophages and the polarization direction of macrophages after Tp stimulation. Methods:Human THP-1 monocyte-derived M0 macrophages were stimulated with the Tp Nichols strain, and the phagocytosis of Tp by macrophages and changes in the intracellular structure of macrophages were observed by transmission electron microscopy and immunofluorescence staining. After 12-hour stimulation by Tp, Tp was removed, the M0 macrophages continued to be cultured for 24, 48, 72 hours and 6 days. Western blot analysis and immunofluorescence staining were performed to determine the expression of the M1 macrophage marker CD86 and M2 macrophage marker CD163, and enzyme-linked immunosorbent assay was conducted to detect levels of M1-type cytokines interleukin (IL) -12 p70, interferon (IFN) -γ, chemokine ligand 10 (CXCL10) , IL-6, tumor necrosis factor (TNF) -α and IL-1β, as well as the M2-type cytokine transforming growth factor (TGF) -β1 in the culture supernatant of macrophages. Dunnett- t test was used for multiple comparisons. Results:As transmission electron microscopy showed, after the stimulation by Tp, the macrophages extended pseudopodia and engulfed Tp, leading to swelling and obviously irregular hyperplasia of endoplasmic reticulum as well as enlargement of mitochondria. Moreover, after additional culture for 24, 48, 72 hours and 6 days, CD86 was highly expressed, but CD163 was lowly expressed in the Tp-treated macrophages; at 24 hours, the supernatant levels of IL-12 p70, IFN-γ, CXCL10, IL-6, TNF-α and IL-1β were significantly higher in the Tp-treated group than in the control group (all P<0.001) , but there was no significant difference in the TGF-β1 supernatant level between the 2 groups ( P>0.05) . Conclusions:After engulfment of Tp, the structures of endoplasmic reticulum and mitochondria in THP-1-derived macrophages markedly changed. Tp could induce the polarization of M0 macrophages into M1 macrophages, and phenotypic switch from M1 to M2 macrophage polarization was not observed within 6 days after Tp stimulation.
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The prevalence of hyperuricemia in elderly population aged over 60 years in China ranges from 5.5%-19.3%.With the population ageing, the number of the patients with hyperuricemia can be expected to grow.Whether elderly patients with asymptomatic hyperuricemia need active uric acid-lowering therapy is still a debatable entity because of lacking relevant clinical guidelines.In this paper, the metabolic process of uric acid, pathophysiologic mechanism of hyperuricemia, the treatment principle of hyperuricemia in combination with different comorbidities, and specific therapeutic schedules for asymptomatic hyperuricemia as well as drug therapy progress were reviewed as follows.
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When having completed the treatments of acute disease ,the hospitalized elderly patients are often not able to return home immediately due to poor physical and mental conditions. They need a period of integrated medical care for recovering independent living ability. Intermediate care provides appropriate treatment and intensive rehabilitation for elderly patients in a relatively short period after acute diseases to restore optimal health ,reduce readmission ,and return self-care ability as far as possible. Intermediate care can fill the gap between acute-term treatment and long-term care. This review is about the development of intermediate care ,the mode and the research of intermediate care in different countries ,equipment configuration and human resource allocation ,and the outlook for intermediate care.
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Objective To study the influencing factors of clinical outcome in elderly acute ischemic stroke (AIS) patients after intravenous thrombolysis.Methods One hundred and fifty-one AIS patients admitted to our hospital for intravenous thrombolysis were divided into good outcome group (n=77) and poor outcome group (n=74) according to their modified Rankin scale score 3 months after the onset of AIS.The baseline data,thrombolysis time window,NIHSS score and ischemic stroke typing before thrombolysis,early symptom improvement,cerebral hemorrhage after thrombolysis were compared between the two groups.Results The serum levels of blood glucose and CRP,NIHSS score≥9 before thrombolysis,incidence of AF and cerebral hemorrhage were significantly higher in poor outcome group than in good outcome group (P＜ 0.05,P＜0.01).Multivariate logistic regression analysis showed that NIHSS score,OCSP typing,blood glucose before thrombolysis,24 h symptom improvement were the independent influencing factors of clinical outcome in elderly AIS patients (OR =1.262,95 ％ CI:1.075-1.482,P =0.005;OR =0.203,95％CI:0.066-0.628,P=0.006;OR=1.264,95％CI:1.042-1.532,P=0.017;OR=25.764,95％CI:5.131-129.361,P=0.000).Conclusion NIHSS score,OCSP typing,blood glucose before thrombolysis and 24 h symptom improvement are the independent influencing factors of clinical outcome in elderly AIS patients after intravenous thrombolysis.
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Objective:To investigate the expression of Smad1 in gastric carcinoma and the influence on the migration ability of gastric cancer cells.Methods:Collected the protein from the gastric cancer tissues and corresponding adjacent tissues,the expression level of Smad1 was detected by Western blot.In HGC-27 gastric cancer cells as the research object,the carrier cells transfected with overexpression of Smad1 (p-EGFP-C1/Smad1) and Smad1 small interfering RNA (Smad1 siRNA),while transfection of p-EGFP-C1 and siRNA control as control.MTT to detect cell proliferation.Cell migration ability was detected with cell scratch test.The expression levels of MMP-9,MMP-2,p-Akt and Akt in ceils were detected by Western blot.Akt signal pathway inhibitor LY294002 (20 μg/ml) in gastric adenocarcinoma ceils,MTT for cell proliferation,cell scratch assay for cell migratior.The expression levels of MMP-9,MMP-2,p-Akt,Akt were detected by Western blot.Results:Smadl in gastric carcinoma was significantly lower than the adjacent tissues (P＜ 0.01).The cell survival rate and migration rate of p-EGFP-C1/Smad1 group were significantly lower than that of p-EGFP-C1 group (P＜0.01).The cell survival rate and migration rate of Smad1 siRNA group were significantly higher than those in the siRNA control group (P＜0.01).The expression levels of Akt protein in P-EGFP-C1,p-EGFP-C1/Smad1,Smad1 siRNA,siRNA control cells did not change.The expression levels of MMP-9,MMP-2 and p-Akt in p-EGFP-C1/Smad1 group were significantly lower than that in p-EGFP-C1 group (P＜0.01).The expression levels of MMP-9,MMP-2 and p-Akt in Smad1 siRNA group were significantly higher than that in control siRNA (P＜0.01).The cell proliferation and migration trends in gastric cancer cells effected by Akt signaling pathway inhibitor consistent with the p-EGFP-C1/Smadl group.Conclusion:Low expression of Smad1 in gastric cancer tissue.Smad1 can inhibit the proliferation and migration of gastric cancer cells,the mechanism of action is related to the Akt signaling pathway.
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Objective To construct the lentivirus plasmids of human Toll like receptor-5(TLR5)and nuclear factor(NF)-κB signaling pathway responsive luciferase and green fluorescent protein(GFP)reporters,and establish a HEK-293 cell line stably expressing human TLR5 and NF-κB responsive reporters. Methods The TLR5 and 5×NF-κB-binding sites genes were cloned to lenti?viral expressing plasmid pWSLV-puro and pWSLV-nanluc-GFP,respectively. The recombinant plasmids,pWSLV-hTLR5-puro and pWSLV-5×NF-κB-nanluc-GFP were respectively transfected with packaging plasmid into HEK293T cells in order to package lentivirus. The lentivirus was used to coinfect HEK-293 cells,and the positive clones stably expressing TLR5 and NF-κB responsive reporter (HEK293-N-T)were generated using colony-purification in present of puromycin and fluorescence activated cell sorting. The cells ex?pressing TLR5 were confirmed by Western blot and immunofluorescence. Additionally,the cells expressing NF-κB responsive reporter were confirmed by fluorescence microscopy and luciferase quantitative assay. Results The results of recombinant plasmids digestion identification and the sequencing of cDNA showed that the sequences inserted into the plasmid and the expected sequences of hTLR 5 and 5×NF-κB-binding sites genes were completely consistent. It was confirmed that the hTLR5 and 5×NF-κB-binding sites genes were correctly inserted into the vectors,and that the recombinant plasmids,pWSLV-hTLR5-puro and pWSLV-5 × NF-κB-nanluc-GFP, were successfully constructed. Additionally,Western blot and immunofluorescence analysis showed that TLR5 were stably expressed in a high level in the HEK293-N-T cells and located in the cell membranes. Moreover,the results of fluorescence microscopy and lucif?erase quantitative assay indicated that the NF-κB responsive reporter could reflect the activation of NF-κB signaling in a dose-depen?dent manner. Conclusion The HEK-293 cell line stably expressing human TLR5 and NF-κB responsive reporter has been successful?ly established and the HEK293-N-T cells can be used for the screening and evaluation of drugs target to TLR5.
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[ ABSTRACT] AIM:To investigate whether kaempferol protects against acute lung injury induced by swine -origin influenza A H9N2 virus via down-regulation of NF-κB signaling pathway .METHODS:BALB/c mice were used to estab-lish the animal model of acute lung injury by nasal inoculation of swine-origin influenza A H9N2 virus.After the interven-tion with kaempferol , the pulmonary edema was evaluated by determining the lung wet weight /dry weight ( W/D) ratio, the pathological changes of the lung tissues were observed , the concentrations of TNF-α, IL-1βand IL-6 in the bronchoalveolar lavage fluid (BALF) were measured, and superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and MDA content in the homogenate of the lung tissues were detected .NF-κB P65 levels were determined by Western blot , and the NF-κB P65 and NF-κB P50 nuclear translocation in the nuclear extracts from mouse lung tissue homogenate was detec-ted by ELISA .RESULTS:Treatment with kaempferol decreased the morality of infected mice , and significantly prolonged the survival time of the infected mice .Kaempferol also relieved the pathological changes of the lung tissues , the lung W/D ratio and the lung index in swine-origin influenza A H9N2 virus-infected mice.Treatment with kaempferol significantly de-creased the infiltration of inflammatory cells including macrophages , lymphocytes and neutrophils in the BALF .The levels of TNF-α, IL-6, IL-1βand MDA and the activity of MPO were also decreased .Treatment with kaempferol also significantly increased the SOD activity .NF-κB P65 levels were decreased , and the NF-κB P65 and NF-κB P50 nuclear translocation in the nuclear extracts from the mouse lung tissue homogenate were also decreased by treatment with kaempferol .CONCLU-SION:The protective effect of kaempferol on the mice with acute lung injury induced by swine -origin influenza A H9N2 vi-rus is related to suppression of the oxidative stress and inflammatory responses by down-regulation of NF-κB signaling path-way.
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Objective To investigate the current situation in construction of WeChat public platform in 9 class A hospitals affiliated to Sichuan Province in Chengdu. Methods The problems and the reasons why they occurred in construction of WeChat public platform in these 9 hospitals were analyzed by literature analysis, interview, Topsis and RSR analysis, and their combination. Results The problems found in hospital WeChat public platform included imperfect management, unmatched construction level and hospital scale, insufficient government policy support and effective supervising mechanisms. Conclusion Hospitals should strengthen the construction and management of their WeChat public platform, innovatively construct their WeChat public platform, win over sufficient government policy support, and improve their supervising mechanisms.
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Objective The current study was aimed to establish an electrically amygdala kindling model of refractory epilepsy in Sprague-Dawley rats, and to study their changes of electrocorticagram ( ECoG ) .Materials and methods Male Sprague-Dawley rats were used in the experiment.Two-polar electrode was implanted into the right amygdala stereotactically.Two weeks after the surgery, electrical stimulations were given to elicit the grade 4 seizure in all animals with the fast kindling protocol.Rekindling was administrated after the first kindling.The after discharge threshold ( ADT) and the number of stimulus were reassessed in the two kindling protocols.ECoG and the behavior of the animals were recorded during the whole experiment.Result The changes of ECoG and behavior: Animals showed stage 1 -3 seizure when the ADT was assessed.While during the kindling period, the animals showed generalized convulsion with stage 4-5 seizure.ECoG showed sharp waves, spike waves, sharp-slow waves and spike-slow waves.Statistical analysis showed that the ADT was not significantly increased at two weeks after kindling ( from 83.33 ±22.29μA to 84.17 ±16.76μA, P=0.923 ) .The number of stimulus given to elicit the stage 4 convulsion was not significantly increased as well ( from 4.41 ±2.27 to 5.58 ±3.96, P=0.231 ) .Conclusions Rapid kindling model of epilepsy in rats is an effective epilepsy model, which is stable for 2 weeks.
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AIM:To investigate the effects of N-acetylcysteine (NAC) on acute lung injury induced by H9N2 swine influenza virus ( SIV) in mice.METHODS: BALB/c mice were used to establish the animal model of acute lung injury by nasal inoculation of H9N2 SIV.The mice were divided into control group (without SIV infection), H9N2 SIV group (inoculation of H9N2 SIV) and NAC group (inoculation of H9N2 SIV plus pretreatment with NAC).The pulmonary edema was evaluated by determining the lung wet weight /dry weight ( W/D) ratio.The pathological changes of the lung tis-sues were observed .The concontrations of TNF-α, IL-1βand IL-6 in bronchoalveolar lavage fluid ( BALF) were meas-ured.The virus titer, T-SOD activity, MPO activity and MDA content in the homogenate of the lung tissues were detected . RESULTS:Treatment with NAC decreased the morality of infected mice , and significantly prolonged the survival time of infected mice .The pathological changes of the lung tissues , the lung W/D ratio and the lung index were relieved when SIV infected the mice treated with NAC .Treatment with NAC significantly decreased the infiltration of inflammatory cells inclu-ding macrophages, lymphocytes and neutrophils in the BALF .The levels of TNF-α, IL-6, IL-1βand MDA and the activity of MPO were also decreased.Treatment with NAC also significantly increased the T-SOD activity.CONCLUSION: The protective effect of NAC on the acute lung injury mouse model is related to suppression of the oxidative stress and inflamma -tory responses .
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Objective To approach the changes of cytosol phospholipase A2α(cPLA2α)and nitric oxide (NO)in patients with chronic obstructive pulmonary disease(COPD)and its significance. Methods One hundred patients with COPD admitted into Department of Critical Care Medicine of Affiliated Wuqing Traditional Chinese Medicine(TCM)Hospital of Tianjin University of TCM were enrolled,and according to the COPD severity grading standards,they were divided into mild group(25 cases),moderate group(25 cases),severe group(26 cases) and extremely severe group(24 cases);simultaneously,90 cases with normal pulmonary function who had taken health examination were chosen and assigned to the healthy control group. The cPLA2α level was detected by enzyme linked immunosorbent assay(ELISA),the level of uric acid(UA),total cholesterol(TC),triacylglycerol (TG)were detected by enzymatic method,and serum NO metabolites(NOx)level was detected by nitrate reductase method. Results Compared with the healthy control group,the serum levels of cPLA2α and UA in patients with different severity of COPD were significantly increased;along with the increase of patient's COPD grade of severity,the cPLA2α,UA levels were gradually increased,while NOx level was gradually decreased in mild, moderate, severe, extremely severe groups〔cPLA2α(ng/L):125.60±8.17, 155.20±6.42, 190.20±9.32, 255.80±11.28 vs. 88.50±7.99;UA(μmol/L):381.23±32.22,434.95±87.71,464.81±52.65,487.45±82.61 vs. 241.95±52.33;NOx(μmol/L):59.90±17.52,45.60±6.17,38.20±4.08,25.70±3.04 vs. 74.90±18.31,all P0.05). The cPLA2αand NOx levels presented significant negative correlation(rs=-0.798,P=0.013). Conclusion The combined examination of blood cPLA2αand serum NOx levels can evaluate the severity degree of COPD patients,and cPLA2αcan be used as a new target index for COPD grading.
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Objective To learn the present situation and bottlenecks of human resources at private hospitals in Sichuan province.Methods Questionnaires,discussions and in-depth interviews were used to learn human resources of 35 private hospitals in the province.Results The findings indicate significant differences among doctors at such hospitals,most of whom age 30-40 years old(45.13％) ; technical titles of the medical workers are low in general,as only 20.08％ of them have vice-senior titles or above; employees are dissatisfied with the remuneration,training setup and culture of their hospitals.Conclusion Private hospitals must enhance training of professionalism,raise payment,improve training setup,and create a positive hospital culture if they want sustained development.In the meantime,hospital regulators should enhance supervision and provide supportive policies.
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Objective To investigate the correlation between benign prostate hyperplasia(BPH) and atherosclerotie related indicators.Methods Totally 125 patients were divided into two groups based on prostate volume(PV):50 cases without BPH (PV≤30 ml) and 75 cases with BPH (PV＞30 ml).Age,body mass index (BMI),triglycerides (TG),total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,glycosylated hemoglobin,prostate specific antigen (PSA),HOMA-IR,bilateral ankle brachial index (ABI) and cardio-ankle vascular index (CAVI) were measured and calculated.All these indicators were compared between two groups.The correlations of these indicators with PV were analyzed.Results BMI,TG,PSA,HOMA-IR and right-CAVI in BPH group were higher than in group without BPH (t=2.177,2.033,3.060,2.859,3.085,all P＜0.05),and right ABI was lower in the BPH group than in group without BPH (t=2.557,P＜0.05).The incidences of diabetes and coronary diseases in BPH group were increased compared with those without BPH (52％ and 36％ vs.30％ and 10％,x2 =5.917,10.648,P =0.015,0.001,respectively).PV was positively correlated with BMI,TG,PSA,right CAVI,left CAVI(r=0.336,0.216,0.556,0.295,0.389,all P＜0.05)by Pearson analysis.Conclusions BPH is closely correlated with insulin resistance and atherosclerosis.Atherosclerosis might cause prostate chronic ischemia and hypoxia,which may play a role in the pathogenesis of BPH.
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@#ObjectiveTo observe the effect of the doctor-led telephone interview on the state of anxiety for outpatients with epilepsy.Methods100 outpatients with epilepsy and state of anxiety were divided into two groups: intervention group (doctor-led telephone interview) and control group (outpatient face-to-face visit in the epileptic clinic), 50 cases in each group. Doctor-let semi-structured telephone interview was performed in the intervention group, while routine face-to-face interview in outpatient was performed in the control group for 6 months. Self-rating Anxiety Scale (SAS) was used to assess the anxiety state before and 6 months after intervention. The state of anxiety and the patients' contents in the two groups were analyzed.ResultsThe scores of SAS in two group decreased 6 months after intervention and the intervention group was better than the control group.ConclusionThe doctor-led telephone interview can improve the state of anxiety for the patients with epilepsy.
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Objective To observe the efficacy of treating cerebral hemorrhage with operation combined with Chinese medicines with the functions of stopping endogenous wind, eliminating phlegm and removing blood stusis. Methods A total of 142 patients after surgery for cerebral hemorrhage were randomly recurited into two groups: a treatment group (n= 41 ) was administrated with Chinese medicines of stopping endogenous wind, eliminating phlegm and removing blood stasis, and a control group (n=41) accepted conventional treatment after the surgery. Results The therapeutic effects in the treatment group was superior to that in control group (X2=13.12, P<0.05) . Conclusion It is effective to treat cerebral hemorrhage with operation combined with Chinese medicines with the functions of stopping endogenous wind, eliminating phlegm and removing blood stasis.