ABSTRACT
The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.
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OBJECTIVE@#To observe the effect of San-Ao Decoction (, SAD) on water metabolism of bronchial asthra model mice.@*METHODS@#Forty-five female BALB/c mice were randomly divided into control, model and SAD groups by a random number table, 15 mice in each group. A composite method with ovalbumin (OVA) sensitization and challenge was developed to establish bronchial asthma model. Mice in the control group were intraperitoneally injected with distilled water without aerosol inhalation challenge. On day 15-22, 0.3 mL SAD was administered via gastric route in SAD group, one time per day, while an equivalent volume of normal saline was used for gastric administration in the control and model groups. Changes in airway resistance in the inspiratory phase (RI-R-Area) were detected using an AniRes2005 system, and 5-h urine output was collected by metabolic cages. Histopathological changes in lung and kidney were observed by hematoxylin-eosin staining. mRNA expressions of aquaporin (AQP) 1 and AQP2 in kidney were detected by reverse transcription-polymerase chain reaction, and the protein expressions of AQP1 and AQP2 in kidney were detected by immunohistochemistry. Enzyme-linked immune sorbent assay was used to detect the OVA-specific endothelium-1 (ET-1), antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), prostaglandin E@*RESULTS@#Compared with the control group, the serum IgE level in model group increased (P<0.01). Following the pathologic changes in lung tissue, no significant change in kidney tissue was observed among 3 groups. Compared with the control group, the mice in the model group showed elevated airway resistance during inhalation phase, higher mRNA and protein expression levels on AQP1 and AQP2 in kidney tissue and higher ET-1 levels in serum, lung and kidney tissues, ADH and ANP in lung and serum, PGE@*CONCLUSION@#San-Ao Decoction can regulate the urine volume through regulating AQP1 and AQP2 expression, and the expression of these in the kidneys might be regulated by ET-1, NO and Ang II.
ABSTRACT
Objective To investigate the infection state and tendency in Tianjin Chest Hospital from 2014 to 2016,and provide scientific basis for making strategy to prevent and control nosocomial infection. Methods With bedside investigation and medical case review,one day every year was selected as the day of investigation to survey the healthcare-associated infections in our hospital during 2014-2016. Data of operative incision, infection condition, the usage of anti-bacterial agents and bacteria detection were collected and organized for further study. Results A total of 2 285 patients were investigated during 2014 to 2016, in which nosocomial infection was found in 55 cases. The total prevalence of healthcare-associated infections was 2.41%. The prevalence rates of healthcare-associated infections in each year were 2.62%,2.63% and 2.05% respectively,and no significant differences between them(χ2=0.750,P>0.05).In the three years, the highest prevalence rates were found in Department of Cardiac Surgery(13.79%),Department of Cardiac Surgery(7.48%) and Department of Endocrine (7.41%) respectively. The lower respiratory tract infection was the main infection site of nosocomial infection (61.11%-78.95%), followed by upper respiratory tract infection, urinary tract infection and blood infection. In 2014-2016, pathogenic detection rates for specimens were 77.78%, 85.71% and 88.89% from patients with nosocomial infection (χ2=0.735,P>0.05). Forty-five strains of pathogen were isolated from 2014 to 2016. The main pathogen was the gram-negative bacteria,and 32 strains were isolated during the three years,which accounted for 71.11%. Six strains of gram-positive bacteria were isolated,which accounted for 13.33%.Seven strains of fungus were isolated,which accounted for 15.56%. The predominant pathogens were Klebsiella pneumonia (10 isolates), Pseudomonas aeruginosa (8 isolates) and Acinetobacter baumannii (5 isolates). The antibiotic utilization rates were 28.40%, 29.17% and 23.74% respectively from 2014 to 2016 (χ2=7.175,P<0.05). In the three years, most of antibiotics were used therapeutically, accounting for 83.39%,14.17% received for prophylactic use,and 2.44% received for both prophylactic use and treatment (χ2=29.151,P<0.05). The rates of bacteria detection in patients who received therapeutic use were 77.02%, 74.42% and 75.77% respectively(χ2=0.306,P>0.05).Conclusion The prevalence of healthcare-associated infection of Tianjin Chest Hospital is maintained at a stable level.The monitoring and prevention of key departments,sites and predominant pathogens should be strengthen, and effective measures for preventing and controlling nosocomial infection should be formulated scientifically,so as to reduce the incidence of nosocomial infection.
ABSTRACT
This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.
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<p><b>OBJECTIVE</b>To investigate whether emodin exerts protective effects on mouse with allergic asthma.</p><p><b>METHODS</b>A mouse model of allergic airway inflflammation was employed. The C57BL/6 mice sensitized and challenged with ovalbumin (OVA) were intraperitoneally administered 10 or 20 mg/kg emodin for 3 days during OVA challenge. Animals were sacrificed 48 h after the last challenge. Inflammatory cell count in the bronchoalveolar lavage fluid (BALF) was measured. The levels of interleukin (IL)-4, IL-5, IL-13 and eotaxin in BALF and level of immunoglobulin E (IgE) in serum were measured with enzyme-linked immuno sorbent assay kits. The mRNA expressions of IL-4, IL-5, heme oxygenase (HO)-1 and matrix metalloproteinase-9 (MMP-9) were determined by real-time quantitative polymerase chain reaction.</p><p><b>RESULTS</b>Emodin induced significant suppression of the number of OVA-induced total inflammatory cells in BALF. Treatment with emodin led to significant decreases in the levels of IL-4, IL-5, IL-13 and eotaxin in BALF and total IgE level in serum. Histological examination of lung tissue revealed marked attenuation of allergen-induced lung eosinophilic inflammation. Additionally, emodin suppressed IL-4, IL-5 and MMP-9 mRNA expressions and induced HO-1 mRNA expression.</p><p><b>CONCLUSION</b>Emodin exhibits anti-inflammatory activity in the airway inflammation mouse model, supporting its therapeutic potential for the treatment of allergic bronchial asthma.</p>