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Patients with spinal cord injury is associated with seriously affected gastrointestinal function and imbalance of intestinal flora, leading to increased inflammation of spinal cord nerves. With the proposal of the theory of gut microbiota-gut-brain axis in recent years, the regulatory role of gut microbiota in the central nervous system and gastrointestinal system has gradually attracted attention. Although a considerable number of studies have focused on the effects of intestinal flora characteristics on spinal cord nerve function repair in patients with spinal cord injury from different perspectives, there are numerous research models for treating spinal cord injury with intestinal flora as intervention targets and remains a lack of unified and effective clinical treatment methods. In this paper, the authors review the research progress in characteristics of intestinal microflora and intestinal microflora-targeted therapeutic methods in patients with spinal cord injury, hoping to provide a reference for the clinical treatment and basic research of spinal cord injury.
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OBJECTIVE To provide referen ce for improving the application of health technology assessment （HTA） in decision-making for health insurance drugs in China. METHODS The application of HTA in decision-making for health insurance drugs in Britain ，France，Germany and Sweden were sorted out and analyzed from two aspects ：the establishment of HTA institutions and the process of HTA. The suggestions for improvement were put forward ，combined with the implementation of HTA in China. RESULTS & CONCLUSIONS Britain，France，Germany and Sweden have set up special HTA institutions ，which perform their respective duties and cooperate closely. During the implementation of HTA ，the above four countries have set different value assessment criteria to screen drugs with “high cost performance ”，all stakeholders actively participate ，make the evaluation results and decisions public ，set up objection handling links ，open a rapid evaluation channel to improve the accessibility of drugs ，and re-evaluate the drugs included in the reimbursement list to ensure the sustainability of medical insurance. It is suggested that China should combine the national conditions ，strengthen the cooperation of HTA institutions ，focus on talent training and comprehensive value assessment criteria ， promote stakeholder ’s participation ， improve the transparency of decision-making，and improve the implementation procedures of HTA in China.
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Objective:To evaluate the effect of preoperative cognitive behavioral therapy (CBT) on pain catastrophizing in the patients with orthopedic trauma.Methods:A total of 120 patients with lower extremity bone trauma, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-28 kg/m 2, with Pain Catastrophic Scale (PCS) score on admission >16, scheduled for surgical treatment, were enrolled.The patients were divided into 2 groups ( n=60 each) by the stratified randomization method based on the type of fracture: CBT group and routine group (group R). Group CBT received CBT for pain through the internet on the day of admission and one day before operation.The patients in both groups underwent reduction and internal fixation of lower extremity fractures under combined spinal-epidural anesthesia.The PCS scores were recorded immediately after admission and on the morning of the operation day.The effective pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia, and occurrence of nausea and vomiting within 48 h after operation were recorded.The visual analogue scale score of the surgical site during activity and occurrence of the score >3 at 3 months after operation and use of opioids within 3 months after operation were recorded. Results:Compared with group R, the PCS score was significantly decreased on the morning of the operation day, the pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia and incidence of nausea and vomiting within 48 h after operation were decreased, the requirement for opioids within 3 months after operation was decreased ( P<0.05), and no significant change was found in VAS score during activity and occurrence of the score >3 at 3 months after operation in group CBT ( P>0.05). Conclusions:Preoperative CBT can reduce the degree of pain catastrophizing and is helpful in increasing the quality of postoperative analgesia in the patients with orthopedic trauma.
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Objective@# To investigate the AIDS-related knowledge, attitudes and practice among university students in a pilot site of AIDS health education in Zhoushan City, so as to provide the reference for AIDS health education in universities.@*Methods@#University students were recruited from Zhejiang Ocean University using a stratified cluster sampling method in 2018 and 2020, and the AIDS-related knowledge, attitudes and practice were collected using a questionnaire survey. @*Results@#A total of 2 862 and 2 850 students were surveyed in 2018 and 2020, including 1 429 ( 49.93% ) and 1 414 ( 49.61% ) male students, respectively. The overall awareness of AIDS-related knowledge was 86.62% and 94.11% in 2018 and 2020, respectively. There were 544 ( 19.01% ) and 394 ( 13.82% ) students that were in favor of one-night stand, 308 ( 10.76% ) and 198 ( 6.95% ) students that were in favor of commercial sexual behaviors, and there were 59 ( 2.06% ) and 34 ( 1.19% ) students that had casual sexual behaviors within one year, and 20 ( 0.70% ) and 8 students ( 0.28% ) with commercial sexual behaviors within one year. There was a significant difference in the awareness of AIDS-related knowledge among students with different years at the university ( P<0.05 ). The lowest awareness of AIDS-related knowledge was seen in freshmen in 2018 ( 81.74% ), and the highest awareness was found in freshmen in 2020 (97.17% ). The proportions of being in favor of one-night stand ( 2018: 31.35% vs. 6.70%; 2020: 22.07% vs. 5.71%; P<0.05 ), being in favor of commercial sexual behaviors ( 2018: 19.91% vs. 2.23%; 2020: 12.09% vs. 1.88%; P<0.05), having casual sexual behaviors within one year (2018: 3.71% vs. 0.42%; 2020: 2.19% vs. 0.21%; P<0.05), and having commercial sexual behaviors within one year ( 2018: 1.33% vs. 0.07%; 2020: 0.50% vs. 0.07%; P<0.05 ) were significantly greater in male students than in female students.@*Conclusions@#The pilot AIDS health education is effective to increase the awareness of AIDS-related knowledge, possess the correct attitudes towards sexual behaviors and reduce high-risk sex behaviors among university students in Zhoushan City. Intensified AIDS health education is recommended among senior and male university students.
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Objective:To investigate relationships between social support and dysfunctional cognition, personality disorder in patients with somatoform disorder.Methods:One hundred and four patients with somatoform disorders and 97 healthy subjects were evaluated with the Social Support Rating Scale (SSRS), Dysfunctional Attitudes Scale (DAS) and Personality Diagnostic Questionnaire (PDQ-4). Social support ratings were compared between patients and healthy controls.The relationship between social support and dysfunctional cognition, personality disorder were analyzed.Results:The scores of social support in all dimensions of patients with somatoform disorder(total score of social support(37.18±8.12), objective social support(8.49±2.83), subjective social support(21.90±5.44), social support utilization(6.79±1.85)) were significantly lower than those in the healthy control group(total score of social support(41.82±6.87), objective social support(9.92±3.38), subjective social support(24.32±4.25), social support utilization(7.59±1.31))( P<0.05). In patients with somatoform disorder, there was a significant negative correlation between the total score of SSRS and the scores of DAS ( r=-0.245, P<0.05) and personality disorder tendency ( r=-0.292, P<0.01). Social support utilization had a significant predictive effect on dysfunctional cognition ( B=-5.384, P=0.007). Conclusion:Social support of patients with somatoform disorder is correlated with dysfunctional cognition and personality disorder tendency, which provides the basis for psychological intervention such as group and family psychotherapy.
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Objective@#To explore the influencing factors of recurrent spontaneous pneumothorax after thoracic closed drainage in adolescents.@*Methods@#From January 2010 to May 2018, 62 young patients with spontaneous pneumothorax treated in School Hospital of Zhejiang Ocean University and referral to superior hospital were selected.The patients were followed up by telephone or clinic for 24 months after discharge, and their general information and recurrence were collected.Logistic regression multivariate analysis was used to investigate the influencing factors of recurrent spontaneous pneumothorax after thoracic closed drainage in adolescents.@*Results@#Sixty-two patients were followed up, 15 patients with recurrence, and the recurrence rate was 24.19%.Univariate analysis showed that age over 20[recurrence and non-recurrence ≤20 years old 11 cases (73.33%), 11 cases (23.40%); >20 years old 4 cases (26.67%), 36 cases (76.59%)], body mass over 19.6kg/m2[recurrence and non-recurrence BMI ≤19.6 10 cases (66.67%), 18 cases (38.30%); BMI>19.6 5 cases (33.33%), 29 cases (61.70%)], smoking[recurrence and non-recurrence smoking 12 cases (80.00%), 14 cases (29.79%); non-smoking 3 cases (20.00%), 33 cases (70.21%)], degree of pneumobula lesions[recurrence and non-recurrence mildly 3 cases (20.00%), 19 cases (40.43%); medium 5 cases (33.33%), 20 cases (42.55%); severe 7 cases (46.67%), 8 cases (17.02%)], pneumothorax[recurrence and non-recurrence a little 2 cases (13.33%), 20 cases (46.81%); massive 13 cases (86.67%), 27 cases (53.19%)] and diameter of pneumobula over 1cm[recurrence and non-recurrence ≤1cm 5 cases (33.33%), 28 cases (61.70%); >1cm 10 cases (66.67%), 18 cases (38.29%)] were associated with recurrence after closed thoracic drainage (χ2=11.857, 5.192, 9.325, 13.522, 9.824, 6.823, all P<0.05). The results of logistic multivariate regression analysis showed that age(OR: 1.224; 95% CI: 0.958-12.142), BMI(OR: 3.463; 95% CI: 0.824-9.024), smoking(OR: 5.000; 95% CI: 1.534-9.852), degree of pneumobulus lesions(OR: 12.041; 95% CI: 6.032-12.174) and pneumothorax(OR: 2.465; 95% CI: 1.627-4.684) were the influencing factors for recurrence after primary spontaneous pneumothorax drainage in adolescents (all P<0.05).@*Conclusion@#Younger than 20 years of age, smoking, pneumobulous lesions and large pneumothorax are risk factors for recurrence after primary spontaneous pneumothorax drainage.
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Objective To explore the influencing factors of recurrent spontaneous pneumothorax after thoracic closed drainage in adolescents.Methods From January 2010 to May 2018,62 young patients with spontaneous pneumothorax treated in School Hospital of Zhejiang Ocean University and referral to superior hospital were selected . The patients were followed up by telephone or clinic for 24 months after discharge,and their general information and recurrence were collected.Logistic regression multivariate analysis was used to investigate the influencing factors of recurrent spontaneous pneumothorax after thoracic closed drainage in adolescents .Results Sixty－two patients were followed up,15 patients with recurrence,and the recurrence rate was 24.19%.Univariate analysis showed that age over 20[recurrence and non －recurrence ≤20 years old 11 cases (73.33%),11 cases (23.40%);＞20 years old 4 cases (26.67%),36 cases (76.59%)],body mass over 19.6kg／m2 [ recurrence and non －recurrence BMI ≤19.6 10 cases (66.67%),18 cases (38.30%);BMI＞19.6 5 cases (33.33%),29 cases (61.70%)],smoking [recurrence and non －recurrence smoking 12 cases ( 80.00%), 14 cases ( 29.79%); non －smoking 3 cases (20.00%),33 cases (70.21%)],degree of pneumobula lesions [recurrence and non －recurrence mildly 3 cases (20.00%),19 cases (40.43%);medium 5 cases (33.33%),20 cases (42.55%);severe 7 cases (46.67%), 8 cases ( 17.02%)], pneumothorax [ recurrence and non －recurrence a little 2 cases ( 13.33%), 20 cases (46.81%);massive 13 cases (86.67%),27 cases (53.19%)] and diameter of pneumobula over 1cm[ recurrence and non －recurrence ≤1cm 5 cases (33.33%),28 cases (61.70%);＞1cm 10 cases (66.67%),18 cases (38.29%)] were associated with recurrence after closed thoracic drainage (χ2 ＝11.857,5.192,9.325,13.522, 9.824,6.823,all P＜0.05).The results of logistic multivariate regression analysis showed that age (OR:1.224;95%CI:0.958－12.142),BMI(OR:3.463;95% CI:0.824－9.024),smoking(OR:5.000;95% CI:1.534－9.852), degree of pneumobulus lesions ( OR:12.041;95% CI:6.032 －12.174) and pneumothorax (OR:2.465;95% CI:1.627－4.684) were the influencing factors for recurrence after primary spontaneous pneumothorax drainage in adolescents (all P＜0.05).Conclusion Younger than 20 years of age,smoking,pneumobulous lesions and large pneumothorax are risk factors for recurrence after primary spontaneous pneumothorax drainage .
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OBJECTIVE@#To establish a non-coated enzyme-linked immunosorbent assay (ELISA) based on zika virus envelope (E) protein for detecting the expression of E protein in infected cells.@*METHODS@#Adherent Vero-143 cells infected with zika virus in a 96-well plate were fixed, and the antibodies against zika virus E protein were added at an optimized concentration to establish the non-coated ELISA method for E protein. The antiviral activities of lignans compound C1 was evaluated using this method. The accuracy of this non-coated ELISA was verified by RT-PCR, and the cross reaction with dengue virus was assessed.@*RESULTS@#After optimization, the background absorbance at 450 nm of uninfected cells was reduced to about 0.20. The antiviral activities of lignans compound C1 detected by this method were basically consistent with the results of RT-PCR. No cross reaction with dengue virus was found in this assay.@*CONCLUSIONS@#A non- coated ELISA method based on zika virus E protein was established, which can be used for screening antiviral agents against zika virus.
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Humans , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin M , Viral Envelope Proteins , Zika Virus , Zika Virus InfectionABSTRACT
OBJECTIVE@#To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.@*METHODS@#MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo.@*RESULTS@#Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation.@*CONCLUSIONS@#Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
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Humans , Antineoplastic Agents , Apoptosis , Bortezomib , Cell Line, Tumor , Drug Synergism , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Proteolysis , Proto-Oncogene Proteins c-bcl-2 , PyrrolesABSTRACT
Objective To analyze the Chengdu municipal social support network of chronic disease elderly to provide refer-ence for systematically building and perfecting the pension system of urban community chronic disease elderly.Methods The self-designed questionnaire and convenience sampling method were adopted to perform the investigation on 234 aged patients with chro-nic disease from Chengdu City.Results The prevalence rates of one,two,three or more chronic diseases were 56.84%,27.78%and 15.38% respectively.The demands for economic,care and spiritual support in the elderly patients with chronic disease were 66.70%,50.00% and 78.20% respectively.The education degree,fixed monthly income,monthly average cost of disease,number and time of suffering from chronic diseases affected the demands for social support.The economic,care and social support degrees were(3.72 ± 1.37),(3.90 ± 1.19)and(3.64 ± 1.08)point respectively.Level of education,marital status,fixed income,duration of illness,and cost of illness affected the social support degree.The economic and care support mainly came from the spouses and chil-dren,but the spiritual support not only came from the inside family,but also the part came from the outside family.Conclusion Constructing a perfect social support network with multiple approaches of community and family is conducive to improve the quality of life in chronic disease elderly.
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OBJECTIVE@#To explore the inhibitory effect of PSB0739 on the formation of semen-derived amyloid fibrils.@*METHODS@#PAP248-286 (440 μmol/L) was incubated with PSB0739 at different concentrations, and at different time points of incubation, aliquots were taken from each sample for Congo red staining to detect the formation of amyloid fibers. The morphology of amyloid fibrils incubated in the presence or absence of PSB0739 was visualized using transmission electron microscope. The effect of PSB0739 on amyloid fibril formation was determined using virus infection assays at different time points, and the surface charges of amyloid fibril incubated with PSB0739 were calculated using a Zeta potentiometer. The cytotoxicity of PSB0739 in Hela cells was determined using MTT assay. The antiviral effect of PSB0738 against HIV- 1 was evaluated by infection assay.@*RESULTS@#PSB0739 inhibited SEVI fibril formation in a dose-dependent manner . At 48 h of incubation, 220 μmol/L of PSB0739 obviously inhibited the formation of amyloid fibrils in 440 μmol/L of SEVI. Transmission electron microscopy revealed that 220 μmol/L PSB0739 prevented PAP248- 286 (440 μmol/L) from forming amyloid fibrils. PSB0739 antagonized SEVI-mediated enhancement of HIV-1 infection, and 1760 μmol/L of PSB0739 completely reversed the positive charge of SEVI ( < 0.05). PSB0739 below the concentration of 62.5 μmol/L showed no obvious cytotoxicity in Hela cells (>0.05). PSB0739 showed a direct anti-HIV activity with an IC of 21.77±5.15 μmol/L.@*CONCLUSIONS@#PSB0739 can inhibit the formation of semen-derived amyloid fibrils .
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Humans , Amyloid , Chemistry , Anti-HIV Agents , Pharmacology , Dose-Response Relationship, Drug , HIV Infections , Drug Therapy , HIV-1 , HeLa Cells , In Vitro Techniques , Microscopy, Electron, Transmission , Purinergic P2Y Receptor Antagonists , Pharmacology , Semen , ChemistryABSTRACT
Objective To observe the inhibitory effect of the extracts of Nidus Collocaliae on avian influenza A H5N1 virus in vitro. Methods Nidus Collocaliae water extract, artificial gastric juice digestion products of Nidus Collocaliae water extract, and artifitial intestinal juice digestion products of Nidus Collocaliae water extract were prepared for the experimental study. 293T cells transfection in vitro was carried out. The effects of 3 kinds of Nidus Collocaliae extracts on H5N1 pseudovirus and VSV-G pseudovirus were determined by luciferase detection kit. Blood clotting response to erythrocyte hemagglutinin subtypes H5, H7, H9 antigens and the inhibitory effects of 3 kinds of Nidus Collocaliae extracts were observed. The effects of 3 kinds of Nidus Collocaliae extracts on neuraminidase activity were determined by neuraminidase inhibitor screen kit. Results The 3 kinds of Nidus Collocaliae extracts had inhibitory effects on H5N1 avian influenza pseudovirus, the effects being enhanced with the increase of the concentrations of Nidus Collocaliae extracts. Of the 3 extracts, artificial intestinal digestion products had the strongest inhibitory effect, while Nidus Collocaliae water extract had the weakest effect. However, Nidus Collocaliae extracts had no obvious effect on VSV-G pseudovirus. The concentration of H5, H7 antigen for positive blood clotting response was 1 ∶ 128, and that of H9 antigen was 1 ∶ 256. The 3 kinds of Nidus Collocaliae extracts at certain concentrations could inhibit blood clotting response to H5, H7, H9 antigen, but had no obvious effect on neuraminidase. Conclusion The anti-H5N1 virus effect of Nidus Collocaliae extracts has been achieved probably through resisting hemagglutinin.
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To study the mechanisms whereby cisplatin suppresses survival of human esophageal squamous cell carcinoma cells.The cytotoxicity of cisplatin in cisplatin-resistant cell line EC109 /CDDP and its parental cell line EC109 was measured by cell viability assay.Western blotting was used to investigate the protein expression of to-tal p53 and phosphorylated p53 at Ser15.Colony formation assay was employed to evaluate the ability of cells to recover from treatments and form colonies.The results indicated that EC109 /CDDP cells were more resistant to cisplatin-induced cytotoxicity than EC109 cells,with the IC50 values of (20.4 ±4.4)μmol /L and (5.7 ±0.1 )μmol /L,respectively.Although cisplatin did not alter the total protein level of p53,it obviously increased the phosphorylation of p53 at Ser15.Cisplatin inhibited survival of both EC109 /CDDP and EC109.Notably,inhibition of p53 by Pifithrin-αsignificantly promoted recovery of cisplatin-treated EC109 and EC109 /CDDP cells to differ-ent degrees.In this respect,p53 protein was found to be activated in response to cisplatin treatment in both EC109 /CDDP and EC109,which may contribute to the cytotoxic effect of cisplatin.
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Objective To investigate the effect of Zhali Nusi Recipe ( ZNR) on hemorheological parameters, blood - lipid metabolism, the activities of superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde (MDA) in brain tissues of cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis. Methods Ninety rats were randomly divided into sham operation group, model group, nimodiping (10.8 mg/kg) group, high-, middle- and low-dose ZNR groups ( in the dosage of 30, 15, 7.5 g/kg, respectively) , 15 rats in each group. Except the sham operation group, the other groups were given intragastric administration of intralipid for 4 weeks, and then were induced into focal cerebral ischemia-reperfusion by middle cerebral artery occlusion with thread-obstruction method. After post-operation medication for 7 days, the rat general situations, the neurological deficiency symptoms, and the water content in brain tissues were observed. The morphological features of brain tissues were observed after HE staining. The blood was taken from the ab dominal aorta to detect the hemorheological parameters and blood lipid levels. Metabolic levels of free radicals in the brain tissue homogenate were also determined. Results Compared with the sham operation group, neurological deficiency scores of the rats and the water content in the brain tissues of model group were significantly enhanced. The hippocampal neurons of model rats presented typical ischemic changes. In the model group, the hemorheological parameters such as whole blood viscosity, plasma viscosity, hematocrit ( HCT) , and erythrocyte aggregation in dexes ( EAI) were significantly increased, and erythrocyte deformation indexes were significantly decreased; the serum levels of total cholesterol ( TC) , triglyceride ( TG) , low-density lipoprotein cholesterol (LDL-C) were significantly increased, and high-density lipoprotein cholesterol ( HDL-C) level was significantly decreased; the activities of SOD and GSH-Px in brain tissues were significantly decreased, and MDA content was increased significantly ( P<0.05 or P<0.01). Compared with the model group, high-, middle-and low-dose ZNR improved the general situations of the cerebral ischemia-reperfusion rats, increased the neurological deficiency scores, reduced the water content in brain tissues, improved the recovery of morphology of cells in cerebral ischemia tissues, reduced whole blood viscosity, plasma viscosity, HCT and EAI of the model rats, promoted erythrocyte deformation indexes, decreased serum TG, TC, LDL-C levels, increased the activities of SOD and GSH-Px in cerebral ischemic tissues, and sig nificantly decreased MDA content (P<0.05 or P<0.01). And high-dose ZNR had the best effect. Conclusion ZNR has certain protective effect on cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis, and the mechanism may be closely related with the improvement ofhemorheology, blood lipid and free radical metabolism in model rats.
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Middle East respiratory syndrome coronavirus (MERS-CoV) has caused outbreaks of SARS-like disease with 35% case-fatality rate, mainly in the Middle East. A more severe outbreak of MERS occurred recently in the Republic of Korea, where 186 people contracted the infections, causing great concern worldwide. So far, there has been no clinically available drug for the treatment of MERS-CoV infection. The potential drugs against MERS-CoV mainly consist of monoclonal antibodies, peptides and small molecular agents. Small molecular agents have an advantage of easier synthesis, lower cost in production and relatively higher stability. There is better chance for those candidates to gain a quick development. This article reviews the progress of developing small molecular MERS-CoV agents.
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In 2012, a new SARS-like coronavirus emerged in the Middle East, namely the Middle East respiratory syndrome coronavirus (MERS-CoV). It has caused outbreaks with high mortality. During infection of target cell, MERS-CoV S protein S1 subunit binds to the cellular receptor (DPP4), and its S2 subunit HR1 and HR2 regions intact with each other to form a stable six-helix bundle to mediate the fusion between virus and target cell membranes. Hence, blocking the process of six-helix bundle formation can effectively inhibit MERS-CoV entry into the target cells. This review focuses on the recent advance in the development of peptidic entry inhibitors targeting the MERS-CoV S2 subunit.
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Aim To study the inhibitory activities of potential new anti-influenza virus agents,3-O-β-chaco-triosyl pentacyclic triterpenoids against the entry of H5N1influenza viruses.Methods Three target com-pounds were designed and synthesized structurally re-lated to the lead compound 3-O-β-chacotriosyl dioscin derivative (1 )with inhibitory activities against H5N1 influenza viruses.The inhibitory activities of these tar-get compounds were tested at a cellular level pseudo vi-rus system targeting H5N1 influenza viruse entry.Re-sults All the compounds 1 a,1 b and 1 c showed po-tent inhibitory activities against the entry of A/Thai-land/Kan353/2004 pseudo virus into the target cells, of which compound 1 b showed the best inhibitory activ-ity with an IC50 value of (1.25 ±0.22)μmol·L-1. Conclusion The SARs analysis of these compounds indicated that replacement of the aglycone moiety of compound 1 with pentacyclic triterpenoids could in-crease antiviral activity.Different types of pentacyclic triterpen as aglycone residue had the significant influ-ence on the inhibitory activity (1 b >1 c >1 a),sug-gesting ursane type of triterpenes was superior to the two other kinds of triterpenes as aglycone residue.
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Aim To study the difference of proteins expression of epithelial cells and stroma of breast canc-er patients.Methods Formalin-fixed paraffin-embed-ded tissue samples from invasive ductal carcionma pa-tients were stained by improved HE staining methods. And the neoplastic epithelium and stroma were micro-dissected using laser capture microdissection and ana-lysed by mass spectrometry.Results Total 43 1 differ-ent proteins were detected by mass spectrometry and there were respectively 384 and 298 different kinds of proteins identified in epithelial cells and stroma.A-mong them,25 1 proteins were commonly expressed in two samples,while the contents of 69 and 60 proteins in stroma were respectively higher or lower than the ones in epithelial cells.The expression level and local-ization of proteins identified in epithelial cells and stro-ma were associated with their roles in development and progression of tumor cells.Conclusions The differen-tial expression proteins between epithelial cells and stroma of invasive ductal carcionma patients may func-tion as biomarkers for breast cancer screenning,diag-nosis and prognosis.
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<p><b>OBJECTIVE</b>To study the inhibitory activities of 3-O-β-chacotriosyl benzyl ursolate and its derivatives as potential new anti-influenza virus agents against the entry of H5N1 influenza viruses into the target cells.</p><p><b>METHODS</b>Four target compounds were designed and synthesized, which were structurally related to the lead compound 3-O-β-chacotriosyl methyl ursolate (1). The inhibitory activities of these compounds were tested at a cellular level psuedovirus system targeting H5N1 influenza viruse entry.</p><p><b>RESULTS AND CONCLUSION</b>The compounds 1b, 1c and 1d showed potent inhibitory activities against the entry of A/Thailand/Kan353/2004 pseudovirus into the target cells, and among them compound 1d showed the strongest inhibitory activity with an IC50 value of 0.96 ± 0.10 µmol/L. The structure-activity relationship analysis of these compounds indicated that when 17-COOH of ursolic acid was esterified, introduction of Me groups rather than aryl groups more strongly enhanced the inhibitory activity. Changing 17-COOH of ursolic acid into amide could increase the antiviral activity and decrease the cytotoxicity of the compounds in MDCK cells.</p>
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Animals , Dogs , Antiviral Agents , Chemistry , Influenza A Virus, H5N1 Subtype , Physiology , Madin Darby Canine Kidney Cells , Structure-Activity Relationship , Triterpenes , Chemistry , Virus InternalizationABSTRACT
<p><b>OBJECTIVE</b>To observe if VIR576, an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin (a1-AT) which inhibits human immunodeficiency virus type 1 (HIV-1) entry into the target cells by interacting with fusion peptide (FP), can also directly inhibit CD4(+) T cell activation in vitro.</p><p><b>METHODS</b>Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation. Both primary CD4(+)CD25(-) T cells from DO11.10 mice and CD4(+) T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.</p><p><b>RESULTS</b>VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation, which bypassed the crosstalk between the CD3-signaling complex and TCR. We furthermore observed that VIR576 could also down-regulate antigen-specific CD4(+) T-cell activation.</p><p><b>CONCLUSIONS</b>Given the high susceptibility of activated CD4(+) T cells in the mucosa to HIV-1 infection, the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4(+) T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.</p>