Calponin is an actin filament-associated regulatory protein expressed in smooth muscle and many types ofnonmuscle cells.Three calponin isoforms 1,2,and 3 are encoded by three homologous genes CNN1,CNN2 and CNN3 in vertebrate species with cell type-specific expression and functions.Besides modulating the activity of smooth muscle myofilaments and contractility,calponin also regulates the functions of actin cytoskeleton in non-muscle cells during cell proliferation,adhesion,migration,differentiation,phagocytosis and fusion.This review focuses on the evolution,tissue and cell type-specific expression,structure-function relationships,transcriptional regulation and relevant mechanisms.

Objective To evaluate the effect on inflammatory mediators and mechanism of dynamic factors on lung injury in a dog model of acute respiratory distress syndrome (ARDS). Method The ARDS dog model was duplicated by instillation hydrochloric acid. The dogs were randomly (random number) divided into six groups: (1) normal control group (N group); (2) ARDS group (M group); (3) low VT (6 mL/kg) at respiratory rate 30, low inspiratory flow 6 mL/(kg·s). (4) large VT (20 mL/kg) at respiratory rate 30, high inspiratory flow 20 mL/kg·s.(5) large VT (20 mL/kg) at respiratory rate 15, high inspiratory flow 17 mL/(kg·s). (6) large VT (20 mL/kg) at respiratory rate 15, low inspiratory flow 10 mL/(kg·s). All the dogs were killed after 4 h ventilation. TNF-α、IL-8, p38 MAPK and NF-κB activity in the lung were measured. Results The expression of IL-8 protein in B and C groups was much higher than that of other groups ( P < 0.01) . There was no significant difference among M, A and D groups (P > 0.05). The gray scale ratio of B group was obviously higher than that of other groups (P < 0.01), except C group (P > 0.05). There was no significant changes among M, A and D groups in TNF-α protein contents. p38 MAPK value of positive staining of B group was the strongest, significantlyhigher than that of D group ( P < 0.01) .The expression of p38 MAPK in B and C groups was much higher than other groups (P <0.01). NF-κB activity in B group (33.56±2.85%) was significantly higher than that in A (10.35±0.6%)、D(7. 11 ± 0.47%)group, but there was no difference between B and C group (30.87 ± 1.16%). Conclusions Ventilation at high tidal volume, high inspiratory flow rate, high respiratory rate could activate p38 MAPK and increase the activity of NF-κB with the result of aggravating the release of inflammatory mediators. p38 MAPK and NF-κB activation are the major mechanisms in the development of VILI.

Objective To investigate the feasibility and efficacy of the intensity modulated radiotherapy (IMRT) with oral S-1 for locally advanced pancreatic cancer.Methods Forty-two patients with locally advanced pancreatic cancer were selected,and the patients were divided into 2 groups by random digits table method with 21 cases each.The patients in treatment group were treated by IMRT combined with oral S-1 40 mg/m2 twice daily from day 1 to day 14 of a 21-d cycle;the patients in control group were treated by IMRT combined with 30 min intravenous infusions of gemcitabine 1 000 mg/m2 on day 1,8,21 and 29.Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d,5 times per week,28 fractions).The dose of intensity modulated radiotherapy was 1.8 Gy/time (5 times/week,50.4 Gy/28 times).The recent curative effect and untoward reaction were assessed at the end of radiotherapy after 4 weeks.Results There were no statistical differences in efficient rate and disease control rate between treatment group and control group:57.1％ (12/21) vs.47.6％ (10/21) and 85.7％ (18/21) vs.76.2％ (16/21),P ＞ 0.05.The neutropenia rate and thrombocytopenia rate in treatment were significantly lower than those in control group:23.8％ (5/21) vs.57.1％ (12/21) and 28.6％ (6/21) vs.66.7％ (14/21),and there were statistical differences (P ＜ 0.05).There were no statistical differences in the incidences of anemia,nausea,vomiting,elevated aminotransferase and fatigue (P＞ 0.05).Conclusions The IMRT with oral S-1 for locally advanced pancreatic cancer is safe and effective.It is worthy of clinical promotion.

Objective To evaluate effects of simultaneous inhibition of mammalian target of rapamycin complex 1(mTORC1)kinase and glycogen synthase kinase-3β(GSK-3β)on phosphorylation of 4E-binding protein-1(4EBP1), cap-dependent translation, as well as survival and apoptosis of melanoma cells. Methods Cultured A375 cells were classified into several groups to be treated with dimethyl sulfoxide (DMSO group), the mTORC1 kinase inhibitor everolimus at a concentration of 5 nmol/L (everolimus group), the GSK-3β kinase inhibitor AR-A014418 at a concentration of 10 μmol/L (AR-A014418 group), or 5 nmol/L everolimus and 10 μmol/L AR-A014418(combined treatment group). After additional culture, Western-blot analysis was performed to measure protein expressions of phosphorylated 4EBP1 (p4EBP1)and survivin in A375 cells, m7GTP pull down assay to estimate interaction between eukaryotic initiation factor-4E (eIF4E)and eIF4G, cell counting kit 8 (CCK8)assay to evaluate cell proliferation, and flow cytometry to detect cell apoptosis. Results Both everolimus and AR-A014418 had inhibitory effects on 4EBP1 phosphorylation and survivin expression. The expressions of p4EBP1-65 and survivin were both significantly decreased in the everolimus group (0.74 ± 0.05 and 0.71 ± 0.06 respectively), AR-A014418 group (0.62 ± 0.06 and 0.58 ± 0.07 respectively)and combined treatment group (0.14 ± 0.04 and 0.09 ± 0.05 respectively)compared with the DMSO group (1.00 ± 0.07 and 1.00 ± 0.06, respectively, all P < 0.001), with the most significant decrease observed in the combined treatment group. As m7GTP pull-down assay showed, the everolimus group, AR-A014418 group and combined treatment group all showed significantly lower relative expression levels of eIF4G(0.72 ± 0.04, 0.67 ± 0.05 and 0.12 ± 0.05 vs. 1.00 ± 0.06, all P < 0.001), but significantly higher relative expression levels of 4EBP1 (1.98 ± 0.16, 2.32 ± 0.17 and 7.58 ± 0.25 vs. 1.00 ± 0.08, all P < 0.001)than the DMSO group, and the combined treatment group showed the lowest eIF4G expression but highest 4EBP1 expression. After 24-hour culture, the proliferation of A375 cells was inhibited by 18.5% ± 1.3% in the everolimus group, 19.8% ± 1.8% in the AR-A014418 group, and 61.2% ± 2.1% in the combined treatment group compared with the DMSO group, with the strongest inhibition noted in the combined treatment group. The inhibitory effects of everolimus and AR-A014418 on cell proliferation increased over time, and showed the same trend at 48 hours. Flow cytometry showed that the apoptosis of A375 cells was accelerated by the 24-hour treatments with everolimus and AR-A014418 alone or in combination, with the apoptosis rate being 14.28% ± 2.18%, 14.57% ± 2.35% and 55.18% ± 6.27% in the everolimus group, AR-A014418 group and combined treatment group respectively, and the combined treatment showed the strongest accelerating effect. Conclusion The combined treatment with everolimus and AR-A014418 can evidently inhibit 4EBP1 phosphorylation and eIF4F complex formation in A375 cells, which then suppress cap-dependent translation and promote apoptosis of melanoma cells.

Objective To enhance the clinical diagnosis efficiency and accuracy of diabetic retinopathy (DR) to facilitate its early finding and diagnosis.Methods Image segmentation method was used to process and analyze DR vessel.Clinical images by fundus fluorescein angiography (FFA) were used as the objects for the research on DR vessel segmentation and extraction.Results Image processing and analysis gained higher definition and accuracy in segmenting the normal retinal image and DR vessel when they were compared with the fundus image and FFA image.Conclusion The method proposed enhances the early diagnosis of DR by processing and analyzing the retinal vessel,and thus contributes to the increased living quality of the patient.

Shuyu Pill is the representative prescription for treating deficiency-essence. This article discussed the consistency of diabetes and deficiency-essence from TCM syndromes and etiology and pathogenesis, and probed into the correlation between Shuyu Pill and diabetic Western medicine of pathomechanism diabetes from the modern pharmacological research on Shuyu Pill. Therefore, it proposed that diabetes has the essence of deficiency-essence;the pathogenesis of diabetes should meet the efficacy of Shuyu Pill; pharmacological effects of Shuyu Pill can affect various pathological mechanism of diabetes, with a purpose to provide new ideas for the clinical treatment of diabetes.

The effect of intrarenal artery injection of bradykinin (BK, 5.0 μg/kg) on multi- and single-unit recordings of afferent renal nerve activity (ARNA) was examined in anesthetized 48 rabbits. The results obtained are as follows. (1) There were two phases of increase in ARNA following intrarenal BK. The early phase occurred immediately while the delayed phase made its appearance about 7 min later. The degree of increase in ARNA of the delayed phase induced by intrarenal BK was more prominent than that in the early phase. BP was actually unaltered following intrarenal BK. (2) By pretreatment with indomethacin (Indo, 5.0 mg/kg), the delayed phase of increase in ARNA induced by intrarenal BK was attenuated, while the early phase was not affected. (3) Pretreatment with L-NAME (30 mg/kg) led the delayed phase to be blocked completely while the early phase was partially decreased. From the above-mentioned observations, it is concluded that intrarenal BK induces a significant increase in ARNA in two phases. The early phase may be due to the direct action of BK and partially due to the NO action, while the delayed phase may be attributed to the action of released prostaglandin and NO as a result of intrarenal BK.

OBJECTIVETo investigate the effect of Jiangtang Yishen Recipe (JTYSR) on high insulin induced cell proliferation of human glomerular mesangial cells (HMCs) and the expression of insulin receptor substrate 1 (IRS-1) and phosphatidylinositol-3-kinase (PI-3K).

METHODSHMCs were divided into 4 groups, i.e., the negative control group, the high insulin model group, the JTYSR group, and the LY294002 group. The concentration of insulin, JTYSR, and LY294002 was respectively confirmed by pre-experiment. Different culture solution was respectively added for different groups. RPMI1640 culture solution was added for HMCs in the negative control group, while HMCs in the rest 3 groups were cultured by 100 nmol/L insulin for 24 h. Meanwhile, HMCs from the JTYSR group and the LY294002 group were exposed to 125 mg/L JTYSR and 80 micromol/L LY294002 respectively for further 48 h. The proliferation of HMCs was detected by MTT and flow cytometry. The protein expression of IRS-1 and PI-3K in HMC was detected by immunohistochemical assay and Western blot. Results The proliferation of HMCs induced by high insulin could be significantly lowered, and the protein expression of IRS-1 and PI-3K could be down-regulated in the JTYSR group and the LY294002 group (P <0.01). Compared with the LY294002 group, the protein expression of IRS-1 and PI-3K could be slightly down-regulated in the JTYSR group (P <0.05).

CONCLUSIONJTYSR could lower high insulin induced proliferation of HMCs, and its mechanism might be related to insulin signaling pathway.

Cell Proliferation ; drug effects ; Chromones ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Insulin Receptor Substrate Proteins ; metabolism ; Mesangial Cells ; physiology ; Morpholines ; Phosphatidylinositol 3-Kinase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction

AIM: To explore the nursing cooperation highlights of eight osteopetrosis patients underwent optic nerve decompression via transsphenoidal microsurgical approach instead of routine pathway, and to improve the quality of nursing cooperation. ·METHODS: We enrolled 8 cases ( left eye in 3 cases, right eye in 5 cases ) of osteopetrosis patients referred from the Eye Hospital of Wenzhou Medical University during February 2012 to November 2016. Patients received ophthalmic examinations including visual acuity and diagnostic imaging tests in pre-operation and post -operation. All eyes were performed surgical optic nerve decompression through endoscopic approach in assist of image guidance system. We retrospectively analyzed the clinical data and surgical cooperation procedure of these cases and summarized nursing cooperation experience. ·RESULTS:The operations of 8 patients were completed successfully without massive hemorrhage. Mean visual acuity improved from pre-operation (2. 5±2. 1) to post-operation (3. 4±1. 9). Cerebrospinal fluid leakage occurred in 1 patient and was instantly repaired during the operation. We performed the nursing strategy as postural drainage, condition monitoring and conscious assessment intra-and post-operation. ·CONCLUSION: It is the critical for this kind of surgery that both circulating nurse's high-skilled cooperation to the connection and operation of the navigation system, to treat with complication during the surgery, and scrub nurse's sufficient preparation of surgical instruments and consumables, proficient equipment delivery, meticulous management, use and maintenance of equipment.

Lycii Cortex, a popular herb medicine in traditional Chinese medicine, is used to treat different inflammation-related diseases. The aim of our work is to find the key constituents inhibiting NF-kappaB, a key regulator of inflammation. In the investigations of cell-based in vitro assays of extracts, we found that both ethyl acetate extract and methanol extract of Lycii Cortex inhibited the TNF-alpha-induced activation of NF-kappaB. Through bioassay-guided fractionation, we identified 4 phenolic amides including trans-N-(p-coumaroyl) tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), and dihydro-N-caffeoyltyramine (4). Four phenolic amides showed differently inhibitory activities on TNF-alpha-induced NF-kappaB activation. Trans-N-caffeoyltyramine (3) was identified as the key component with an IC50 of 18.41 micromol x L(-1). It was suggested that the hydroxyl group at C-3 in trans-N-caffeoyltyramine might be a key binding site and its C-7,8-double bond might play an important role on NF-kappaB inhibitory activities as the link of the conjugation of pi electrons leading to a partial planar conformation. It might be inferred that the biological activity of compound 3 is attributed to the structure of Michael reaction acceptor containing alpha, beta-unsaturated ketones and benzene along with hydroxyl group in o-diphenol.
Biological Assay ; Cell Line ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Inflammation Mediators ; antagonists & inhibitors ; immunology ; Lycium ; chemistry ; Molecular Structure ; NF-kappa B ; antagonists & inhibitors ; immunology