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Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
ABSTRACT
Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
ABSTRACT
Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro- and anti-inflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
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Objective:To observe the efficacy of laminoplasty with reconstructing of cervical extensor attachment on cervical spondylotic myelopathy (CSM) involving C2 segment. Methods:From March, 2014 to January, 2017, 46 cases with CSM involving C2 accepted surgery in our hospital. They were divided into two groups according to the surgical methods. Control group (n = 21) accepted traditional laminoplasty, while observation group (n = 25) accepted laminoplasty with extensor muscle attachment point reconstruction. They were assessed with Japanese Orthopaedic Association (JOA) spinal scores, cervical range of motion (ROM), cervical curvature, areas of posterior cervical muscles and axial symptoms. Results:There was no significant difference at operative time and intraoperative blood loss (t < 0.863, P > 0.05) between groups. After surgery, the JOA score increased in both groups (F > 24.961, P < 0.001), but there was no significant difference between two groups (t < 0.282, P > 0.05). ROM varied little in both groups (F < 0.931, P > 0.05). The cervical neutral position curvature decreased in the control group (F = 8.241, P < 0.01), but not in the observation group (F = 2.705, P > 0.05). The areas of posterior muscle decreased in control group (t = 2.678, P < 0.05), but not in the observation group (t = 0.854, P > 0.05). The incidence of axial symptoms was less in the observation group than in the control group (Z = -2.192, P < 0.05). Conclusion:Laminoplasty could relieve the spinal compression at C2 segment and promote the recovery of neurological function, and it can do better in cervical curvature and posterior cervical muscle atrophy as combination with reconstruction of extensor muscle attachment, to reduce the axial symptoms.
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Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.
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Objective To investigate the expressions of octamer-binding transcription factor 4 (Oct4) and phosphorylated-protein kinase B (p-Akt) proteins in colorectal cancer and their clinical significances, in order to explore the roles of Oct4 and p-Akt in the staging and grading of colorectal cancer. Methods Immunohistochemical technique was used to examine the expression of Oct4 and p-Akt proteins in 78 cases of colorectal cancer in Wuxi Second Hospital of Traditional Chinese Medicine and Wuxi First People's Hospital from January 2011 to December 2016. Relationship between expressions of Oct4 and p-Akt proteins and clinicopathological parameters were analyzed. Results The positive rate of Oct4 in tumors was 74.36 % (58/78), which was obviously higher than that in normal tissues [35.90 % (20/78), χ2= 23.32, P < 0.01]; and the positive rate of p-Akt in tumors was 67.95 % (53/78), which was obviously higher than that in normal tissues[28.21 %(25/78),χ2=24.68,P <0.01].The double positive and negative expression rate of these two proteins accounted for 80.8 %(63/78), with a linear positive correlation (r= 0.455, P < 0.000 1). In 78 cases of colorectal cancer, the expression of Oct4 protein was correlated with histological grade, lymph node metastasis, and Duke staging (all P < 0.05), and the expression of p-Akt protein was correlated with histological grade and lymph node metastasis (both P < 0.05). The multivariate logistic regression analysis showed that the expression of Oct4 protein was related to histological grade and Duke staging(both P<0.05),and the expression of p-Akt protein was only related to lymph node metastasis (P<0.05). Conclusion The combined detection of Oct4 protein and p-Akt protein has reliable and important clinical significance for judging the histological grade,lymph node metastasis and Duke staging of colorectal cancer.
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<p><b>BACKGROUND</b>Surgical treatment of thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) is technically demanding, and the results tend to be unfavorable. Various operative approaches and treatment strategies have been attempted, and posterior decompression with transforaminal thoracic interbody fusion (PTTIF) may be the optimal method with which the anterior-posterior compression was removed in one step. It is comparatively less traumatic with fewer serious complications.</p><p><b>METHODS</b>Sixteen patients with thoracic myelopathy due to concurrent OLF and OPLL at the same level underwent PTTIF. We investigated clinical outcomes and neurological improvements. Magnetic resonance imaging (MRI) was performed on all patients preoperatively and postoperatively, and intramedullary signal changes were evaluated.</p><p><b>RESULTS</b>The mean operating time was 275 minutes, and the mean operative bleeding amount was 1031 ml. Cerebrospinal fluid leakage occurred in three patients and healed well after repair. Neurological symptom deterioration occurred in one patient, but the patient recovered to nearly the preoperative level after methylprednisolone treatment. The follow-up period ranged from 28 to 47 months. The mean score on the Japanese Orthopedic Association scale improved from 4.3±1.2 preoperatively to 7.3±1.7 at 3 months postoperatively to 8.5±1.5 at the final follow-up (P < 0.01), with a recovery rate of (63.6±20.0)%. Postoperative images showed a significant improvement in local kyphosis (P < 0.01). Eleven patients (68.8%) showed increased signal intensity (ISI) on preoperative T2-weighted MRI. At the final follow-up, the intramedullary ISI totally recovered in five patients. Neurological improvement was worse in patients with persistent ISI than in the other patients (P < 0.05).</p><p><b>CONCLUSIONS</b>PTTIF is an effective therapeutic option for combined OPLL and OLF and provides satisfactory neurological recovery and stabilized thoracic fusion through a single posterior approach. Intramedullary signal changes do not always indicate a poor prognosis; only irreversible ISI is correlated with a poor clinical result.</p>