Neuropathological, clinical epidemiology and animal models studies provide clear evidence for the activation of neuroinflammation in Alzheimer's disease (AD), and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked with reduced risk to develop the disease. But the clinical trials got a negative outcome with traditional NSAIDs treating AD. The therapeutic effects of NSAIDs on Alzheimer's disease are still not clear based on the present research. Profound study for anti-inflammatory mechanisms and standardized clinical trials are needed. As cause and effect relationships between neuroinflammation and AD are being worked out, the challenge is how to realize the effect of traditional NSAIDs on treating AD.
Alzheimer Disease ; drug therapy ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Humans ; Inflammation ; drug therapy

OBJECTIVETo evaluate the effect of the platelet-derived growth factor-BB (PDGF-BB) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMC) in SD rats.

METHODSCCSMCs were primarily cultured in the modified tissue sticking medium and subjected to immunofluorescence assay. The cells were divided into a blank control and four PDGF-BB groups, the latter exposed to 5, 10, 20, and 40 ng/ml of PDGF-BB, respectively, for 24 hours, and the cells in the 20 ng/ml PDGF-BB group treated for 24, 48, and 72 hours. The the relative expressions of α-SMA, SMMHC, calponin, and OPN mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR).

RESULTSThe α-SMA positive rate of the CCSMCs was over 95%. Compared with the blank control group, the expression levels of α-SMA, SMMHC, and calponin mRNA were significantly decreased (P < 0.05) while that of OPN mRNA remarkably increased (P < 0.05) in the PDGF-BB groups. The 20 ng/ml PDGF-BB group also showed significantly downregulated expressions of α-SMA, SMMHC, and calponin mRNA (P < 0.05) and upregulated expression of OPN mRNA (P < 0.05) at 24, 48, and 72 hours.

CONCLUSIONPDGF-BB can induce the transformation of the phenotype of CCSMCs in SD rats from the contractile to the synthetic type.

Actins ; metabolism ; Animals ; Calcium-Binding Proteins ; metabolism ; Cell Culture Techniques ; Cells, Cultured ; Male ; Microfilament Proteins ; metabolism ; Muscle Contraction ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Myosin Heavy Chains ; metabolism ; Penis ; cytology ; drug effects ; metabolism ; Phenotype ; Proto-Oncogene Proteins c-sis ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

With an objective to provide an experimental basis for scientific officinal of Schisandrae Sphenantherae Fructus, this research uses UPLC-TQ/MS method to analyze 7 different kinds of lignan in 70 batches of Schisandra sphenantherae Fructus samples from 9 regions. The results showed that in the area south of Qinling mountains, Schisandrae sphenantherae Fructus from Zhashui county and Shanyang county of Shangluo mainly contained schisantherin A and deoxyschizandrin. However, Schisandrae sphenantherae Fructus from Mei county of Baoji, Shiquan county and Ningshan county of Ankang, and Lueyang county of Hanzhong, mainly contained anwuligan. Samples from Ningshan county also consists relatively high level of deoxyschizandrin. In the central area of Qinling mountains and the Daba mountains, Schisandrae Sphenantherae Fructus from Nanzheng county of Hanzhong mainly contained schisanhenol and deoxyschizandrin. In conclusion, the kinds and level of lignan differ significantly in Schisandrae sphenantherae Fructus produced in different regions. In practical application, Schisandrae Sphenantherae Fructus produced in different regions should be distinguished and differently applied based on their main effective components corresponding to different diseases, which can lead to the best clinical use.
China ; Drugs, Chinese Herbal ; chemistry ; Fruit ; chemistry ; Lignans ; chemistry ; Quality Control ; Schisandra ; chemistry

This study aimed to investigate the role and mechanism of sappanone A (SA) in regulating renal ischemia-reperfusion injury (IRI) in rats. The animal experiment has been approved by the Ethics Committee of Suzhou Wujiang District Children's Hospital (approval number: 2022010). First, hematoxylin-eosin (H&E) staining was used to evaluate the effects of SA on IRI, and renal damage was scored. Serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C (Cystatin C) were analyzed. The effect of sappanone A on the apoptosis of renal tubular epithelial cells induced by IRI was analyzed by TUNEL staining. Protein expression levels of p-JNK/JNK, p-ERK/ERK, Bcl2, Bax and cleaved-caspase 3 in renal tissues were detected by Western blot. Finally, H&E staining, serological analysis, TUNEL staining and Western blot were used to determine whether JNK activator anisomycin could reverse the effect of SA on IRI in rats. The results showed SA significantly reduced the renal tubule injury caused by ischemia-reperfusion, and decreased the level of SCr, BUN and Cys C in serum. TUNEL staining showed that SA significantly reduced the apoptosis of renal tubular epithelial cells induced by IRI. Western blot analysis of kidney tissue showed that SA significantly promoted the expression of apoptosis inhibiting protein Bcl2 and inhibited the expression of apoptosis-promoting proteins Bax and cleaved-caspase 3. Further analysis elucidated that SA did not affect the phosphorylation of ERK but decreased the phosphorylation of JNK. Finally, H&E staining, serological analysis, TUNEL staining and Western blot confirmed that JNK activator anisomycin could reverse the alleviating effect of SA on IRI in rats. The above findings suggest that SA could alleviate IRI in rats by inhibiting JNK phosphorylation.

OBJECTIVETo investigate the protective effects of trimetazidine on rabbit myocardium in ischemia and reperfusion.

METHODSFourty rabbits were divided into five groups randomly: normal control group, ischemia control group, ischemia and drug intervention group, reperfusion control group, reperfusion and drug intervention group. Ischemia lasted for 30 minutes and reperfusion was given for 30 minutes. Serum CPK, SOD activities and MDA concentrations were measured in each group and ischemia tissue ATP concentrations were also measured. Heart tissue was examined with electron microscope in each group.

RESULTS(1) Serum concentrations of MDA in ischemia and drug intervention group were significantly different from those in ischemia control group [(4.09+/-0.40 vs 4.79+/-0.92)nmol/ml, P<0.01], serum activities of CPK [(1322+/-1148 vs 1498+/-190) NU/ml], SOD[(324+/-71 vs 288+/-54)NU/ml] were not significantly different between ischemia and drug intervene group and ischemic control group (PP>0.05,respectively). (2) Serum activities of CPK [(1512+/-226 vs 1904+/-203) NU/ml], SOD[(213+/-71 vs 119+/-55) NU/ml], concentrations of MDA [(6.09+/-0.69 vs 7.43+/-0.20)nmol/ml] and concentrations of ATP[(1.401+/-0.248 vs 0.629+/-0.175) micromol/g] in ischemia heart tissue of reperfusion and drug intervention group were significantly different from those in reperfusion control group (P<0.001 - 0.01 respectively). (3) There were significant differences in electron microscopic observation between intervention group and control group.

CONCLUSIONTrimetazidine can improve cardiac mitochondrial metabolism and scavenge oxygen free radicals. Trimetazidine has cardioprotective function during ischemia and reperfusion.

Adenosine Triphosphate ; analysis ; Animals ; Creatine Kinase ; blood ; Female ; Male ; Malondialdehyde ; blood ; Mitochondria, Heart ; drug effects ; ultrastructure ; Myocardial Reperfusion Injury ; prevention & control ; Protective Agents ; pharmacology ; Rabbits ; Superoxide Dismutase ; blood ; Trimetazidine ; pharmacology

Objective To investigate the feasibility and reliability of the measurement of critical anatomic landmarks of endoscopic endonasal anatomy of pterygopalatine fossa and infratemporal fossa using multislice spiral computed tomography (MSCT), and to illustrate the spatial relationship of the surgical landmarks in pterygopalatine fossa and infratemporal fossa through an endoscopic endonasal view and radiological images. Methods Included in this study were eleven fixed cadaver heads (22 pterygopalatine fossa and infratemporal fossa), which were prepared from MSCT scans for establishing a spatial coordinates system to calculate the radiological anatomic data and attaining 3D reconstruction image, and also were anatomically dissected to get anatomic data. The anatomic data in two groups were compared, the endoscopic and radiological images of the same regions acquired during the endoscopic endonasal approaches observed.Results The distance ((-x) ± s) from nasal columella to sphenopalatine foramen, pterygoid canal, foramen rotundum, foramen ovale, foramen spinosum, carotid canal, foramen lacerum in radiological group were:(68.83±3.00), (72.49±2.88), (75.26 ±3.14), (88.55±5.00), (95.19±4.31), (106.76±3.77), (88.16 ±2.87) mm and in anatomic group were: (68.90 ±3.04), (72.73 ±3.08), (75.44 ±3.07), (89.75 ±4.13), (96.22±3.37), (106.68 ±3.75), (88.47 ±2.64) mm. There was no statistical difference between two groups(t value were -0.856, -1.134, -0.920, - 1.923, - 1.903,2.820 and 1.209, respectively, all P > 0.05 ). Sphenopalatine foramen, pterygoid canal, foramen rotundum, foramen ovale, foramen spinosum, foramen lacerum, carotid canal were the corresponding anatomic structures in endoscope and radiology, which provided the surgeons with anatomic landmarks to identify the spatial relationship of the surgical structures in pterygopalatine fossa and infratemporal fossa.Conclusions MSCT measurements of anatomic landmarks are feasible and reliable, can be used in clinical individualized surgery. The corresponding anatomic structures of endoscopic and radiological landmarks provide useful reference to surgeons when operating in these areas through an endoscopic endonasal approach.

OBJECTIVETo observe the effects of two main isoflavones, daidzein and genistein on the bone-nodule formation in rat calvaria osteoblasts in vitro.

METHODSOsteoblasts obtained from newborn Sprague-dawley rat calvaria were cultured for several generations. The second generation cells were cultured in Minimum Essential Medium supplemented with ascorbic acid and Na-beta-glycerophosphate for several days, in the presence of daidzein and genistein, with or without the estrogen receptor antagonist ICI 182780. Number of nodules was counted at the end of the incubation period (day 20) by staining with Alizarin Red S calcium stain. The release of osteocalcin, as a marker of osteoblast activity, was also determined on day 7 and day 12 during the incubation period.

RESULTSCompared with the control, the numbers of nodules were both increased by incubation with daidzein and genistein. 17 beta-estradiol was used as a positive control and proved to be a more effective inducer of the increase in bone-nodules formation that daidzein and genistein. The release of osteocalcin into culture media was also increased in the presence of daidzein and genistein, as well as 17 beta-estradiol on day 7 and day 12 (day 12 were higher). The estrogen receptor antagonist ICI 182780 completely blocked the genistein- and 17 beta-estradiol-induced increase of nodule numbers and osteocalcin release in osteoblasts. However, the effects induced by daidzein could not be inhibited by ICI 182780.

CONCLUSIONThese findings suggest that geinistein can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts. The effects, like those induced by 17 beta-estradiol, are mediated by the estrogen receptor dependent pathway. Daidzein also can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts, but it is not, at least not merely, mediated by the estrogen receptor dependent pathway.

Animals ; Cells, Cultured ; Genistein ; pharmacology ; Isoflavones ; pharmacology ; Osteoblasts ; cytology ; drug effects ; metabolism ; Osteocalcin ; biosynthesis ; Osteogenesis ; drug effects ; Rats ; Rats, Sprague-Dawley ; Skull ; cytology ; drug effects ; metabolism

OBJECTIVETo explore the diagnostic values of vestibular autorotation test (VAT) for patients with vertebrobasilar insufficiency (VBI).

METHODSVAT and videonystagmography ( VNG) were performed on 73 patients with VBI and 48 patients with peripheral vestibular lesions (contrast group). Parameters analyzed included Gain, phase and asymmetry of VAT, as well as the canal paresis (CP) of caloric test and results of optokinetic-pursuit tests in VNG. Positive result of the test could be defined if anyone of the parameters was abnormal.

RESULTSFor VAT test, Gain was enhanced in VBI group and was reduced in contrast group. In VBI group and contrast group, Gain enhanced showed in 47 (64.4%) cases and 5 (10.4%) cases, respectively (chi2 = 31.19, P < 0.01). Simultaneity, Gain reduced in 11 cases (15.5%) and 22 cases (45.8%), respectively (chi2 = 13.82, P < 0.01). But there was no statistics significant for results of the parameters of phase, asymmetry and integration between two groups. For VNG test, results with optokinetic-pursuit tests were more abnormal in VBI group than that in contrast group, which showed central lesions characteristics. Forty-four cases (60.3%) in VBI group and 10 cases (20.8%) in control group showed central lesions results with optokinetic-pursuit tests and visual fixation test (chi2 = 15.89, P < 0.01). Unilateral or bilateral CP showed in 33 cases (68.6%) in control group and 51 cases (69.9%) in VBI group with caloric test.

CONCLUSIONSGain of VAT is mostly enhanced in VBI group, and Gain as a main characteristic is reduced in patients with peripheral vestibular lesions. The Gain parameter is availability for assessing characteristics of vestibular lesions. Phase and asymmetry can be used to assess the vestibular function but can not indicate the characteristics of vestibular lesions.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; Vertebrobasilar Insufficiency ; complications ; physiopathology ; Vertigo ; etiology ; physiopathology ; Vestibular Function Tests ; methods ; Young Adult

OBJECTIVETo estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology.

METHODSCadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD.

RESULTSThe cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG; and ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 microg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected.

CONCLUSIONBMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

Acetylglucosaminidase ; urine ; Albuminuria ; urine ; Biomarkers ; urine ; Cadmium ; toxicity ; urine ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Occupational Exposure ; Spectrophotometry, Atomic ; beta 2-Microglobulin ; urine

Adult ; Female ; Femoral Fractures ; surgery ; Fracture Fixation ; methods ; Humans ; Knee Injuries ; surgery ; Male ; Middle Aged ; Tibial Fractures ; surgery