ABSTRACT
AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.
Subject(s)
Autophagy-Related Protein-1 Homolog/antagonists & inhibitors , Autophagy/drug effects , Neuroprotective Agents/pharmacology , Palmitic Acid/pharmacology , Stearic Acids/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Autophagy/physiology , Autophagy-Related Protein-1 Homolog/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Male , Mice , Mice, Inbred C57BL , Neuroprotective Agents/therapeutic use , PC12 Cells , Palmitic Acid/therapeutic use , Phosphorylation/drug effects , Phosphorylation/physiology , Rats , Signal Transduction/drug effects , Signal Transduction/physiology , Stearic Acids/therapeutic use , TOR Serine-Threonine Kinases/metabolismABSTRACT
Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.
Subject(s)
Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/physiopathology , Palmitic Acid/therapeutic use , Stearic Acids/therapeutic use , Aging/blood , Aging/pathology , Animals , Behavior, Animal , Blood Glucose/metabolism , Body Weight , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cognitive Dysfunction/blood , Diabetes Mellitus, Experimental/blood , Exploratory Behavior , Male , Memory Disorders/blood , Memory Disorders/complications , Memory Disorders/physiopathology , Mice , Repressor Proteins/metabolism , Social Behavior , Spatial MemoryABSTRACT
OBJECTIVE: To explore clinical safety and efficiency of electroacupuncture combined with acupoint-injection of botulinum toxin A for the treatment of muscle spasticity by spinal cord injury. METHODS: Thirty-eight patients with muscle spasticity by spinal cord injury were treated from December 2006 to December 2009 including 26 males and 12 females, with an average age of 45.4 years old ranging from 21 to 68 years. The patients were randomly divided into 3 groups according to admission time, 13 patients in group A were treated with electroacupuncture combined with acupoint-injection of botulinum toxin A, and 13 patients in group B were treated with acupoint-injection botulinum toxin A and 12 patients in group C were treated with electroacupuncture. After 6 months these patients were evaluated by improved muscle Ashworth scoring (MAS) and clinical spasticity index (SCI). RESULTS: Thirty-eight patients were followed-up at 6 months after the treatment. The result showed that the MAS scores of group A, B, C before treatment were (3.10 +/- 0.14), (3.20 +/- 0.17), (3.10 +/- 0.16) respectively and the CSI scores were (14.10 +/- 0.14), (14.30 +/- 0.11), (14.20 +/- 0.12) respectively; there were no statistical different among the three groups (P > 0.05). After 6 months of treatment, the MAS scores were (1.10 +/- 0.16), (2.10 +/- 0.13), (2.00 +/- 0.14) respectively and the CSI scores were (9.10 +/- 0.11), (12.10 +/- 0.14), (13.10 +/- 0.12) respectively. The MAS scores and CSI scores of group A were better than the other two groups (P < 0.05). CONCLUSION: The combination of Chinese hydropower needles and acupoints with BTX-A injection can achieve a comprehensive treatment and reduce pain and improve life quality quickly. The electroacupuncture combined with acupoint-inject botulinum toxin A is a noval safe and effective technique for the treatment of muscle spasticity by spinal cord injury.
Subject(s)
Acupuncture Points , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/therapeutic use , Electroacupuncture/methods , Muscle Spasticity/complications , Muscle Spasticity/therapy , Spinal Cord Injuries/complications , Adult , Aged , Electroacupuncture/adverse effects , Female , Humans , Injections , Male , Middle Aged , Muscle Spasticity/drug therapy , Muscle Spasticity/physiopathology , Safety , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Primary non-Hodgkin's lymphoma in lung is very rare, and the most common among them is mucosa-associated lymphoid tissue lymphoma (MALToma), whose clinical features and laboratory characteristics are poorly defined, making diagnosis difficult. The purpose of this study was to study the diagnosis and treatment of pulmonary MALToma. METHODS: The clinical data of 12 patients treated for MALToma between August 1992 and December 2005 were analyzed. RESULTS: No specific symptoms or signs, or results of bronchoscopy, ultrasonagraphy or bone marrow examination could be found in the 12 patients. Only radiography was useful in diagnosis, though the final diagnosis of all the patients was based on histology and immunohistochemistry. Two patients also had gastric MALToma. Operations were performed on 6 patients, including 5 radical operations and 1 partial resection: 4 patients also received adjuvant chemotherapy. One patient experienced recurrence 152 months after the operation, while the other 5 patients have survived disease-free. Four patients were treated with chemotherapy alone, two of whom experienced complete remission and the others partial remission. The final 2 patients received no treatment and had survived for 7 and 27 months respectively. All the patients were still alive at the most recent follow-up, 7 to 160 months (mean 71.3 months). CONCLUSIONS: Except radiography, no specific clinical manifestations could be identified for pulmonary MALToma. The final diagnosis should be based on histology and immunohistochemistry. Several treatment methods can be used to achieve good outcomes.
Subject(s)
Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/therapy , Adult , Aged , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lung/drug effects , Lung/pathology , Lung/surgery , Male , Middle Aged , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the effects of ginaton against ischemia-reperfusion injury on the autograft after lung autotransplantation. METHODS: Models of lung autotransplantation were established in 18 New Zealand rabbits were established. The 18 rabbits were randomly divided into 3 equal groups: group of simple ischemia-reperfusion (group I/R), undergoing ischemia by blocking the left pulmonary artery for 2 h and then re-perfusion for 90 min; group with perfusion of low potassium dextran solution (group LPD), undergoing perfusion of LSD solution before ischemia; and group with treatment of ginaton (group LPD + E), undergoing intravenous injection of ginaton 15 min before ischemia. Arterial blood samples were collected before ischemia, and 15, 60, and 90 min after re-perfusion to examine the alveolar oxygen pressure (PaO2). Serum tumor necrosis factor-alpha (TNF-alpha) was monitored before ischemia, and 30, 60, and 90 min after re-perfusion. Then the left lungs were taken out to undergo detection of dry/wet ratio (D/W), pathological examination, and contents of myeloperoxidase (MPO) and the malondialdehyde (MDA) in the lung tissues. RESULTS: (1) The PaO2 decreased significantly after reperfusion in all groups. And the PaO2 values at different time points of Group LPD + E were all significantly higher than those of Group I/R (all P < 0.01), however, there were no significant differences between Group LPD and Group LPD + E. (2) The TNF-alpha level after reperfusion increased in Group I/R and Group LPD, while in Group LPD + E it increased only 60 min and 90 min after the reperfusion. The TNF-alpha levels after reperfusion at all time points of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.05). (3) The MPO and MDA levels at all time points after re-perfusion of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.01). (4) The value of D/W ratio of Group LPD + E was significantly higher than those of the other 2 groups (both P < 0.01). (5) Pathological examination showed that the lung tissue lesion of Group I/R was severe. Interstitial inflammatory cell infiltration, intra-alveolar inflammatory cell aggregation, exudation and even hemorrhage could be observed. The pathological lesion of Group LPD + E was mild, no significant inflammatory cell infiltration or exudation was observed. CONCLUSION: Ginaton provides a protective effect against ischemia-reperfusion injury on the autograft after lung autotransplantation. The mechanism may be related with antioxidation, inhibition of neutrophil aggregation, and TNF-releasing.