Current understanding of metal ions in the pathogenesis of Alzheimer's disease.

Background: The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer's disease (AD), the most common neurodegenerative disorder in the elderly. Main body: Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-ß (Aß) overproduction by activating ß- or γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3ß (GSK-3ß), cyclin-dependent protein kinase-5 (CDK5), mitogen-activated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aß and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aß/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients. Conclusion: The metal ions imbalance induces Aß and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA).</p><p><b>RESULTS</b>High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment.</p><p><b>CONCLUSION</b>JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.</p>

Effect of formula of removing both phlegm and blood stasis in improving hemorheology and blood fat of mini-swine with coronary heart disease of phlegm-stasis cementation syndrome / 中国中药杂志

<p><b>OBJECTIVE</b>To observe effect of formula of removing both phlegm and blood stasis (TYTZ) in improving hemorheology and blood fat of mini-swine with coronary heart disease of phlegm-stasis cementation syndrome.</p><p><b>METHOD</b>Thirty-six Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Shujiangzhi group and TYTZ groups with doses of 2.0, 1.0 and 0.5 g x kg(-1), with six mice in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. In the 8th week after the operation and administration, the changes in hemorheological parameters, serum lipid level, myocardial ischemia level and range were observed.</p><p><b>RESULT</b>Compared with the normal control group, the model group showed significant increase in serum TC, TG, LDL-C and VLDL-C levels (P < 0.01), whole blood viscosity under the shear rate of 5 s (-1) and 60 s (-1) (P < 0.01), and myocardial ischemia degree and range (P < 0.01). Compared with the model group, TYTZ groups revealed significant decrease in myocardial ischemia degree and range (P < 0.01), serum TC, TG, LDL-C and VLDL-C levels (P < 0.05 or P < 0.01) and whole blood viscosity under the shear rate of 5 s(-1) and 60 s(-1) (P < 0.05).</p><p><b>CONCLUSION</b>TYTZ could improve the abnormal hemorheology in Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome, and regulate serum lipid, with a certain efficacy for coronary heart disease of phlegm-stasis cementation syndrome.</p>

Experimental study of jiangtang xiaozhi tablet on decreasing the levels of blood glucose and serum lipids in transgenic mice with diabetes mellitus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Jiangtang Xiaozhi Tablet (JTXZT) on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with diabetes mellitus (DM).</p><p><b>METHODS</b>KK-Ay transgenic mice were fed with high fat diet to induce DM obesity model. The C57 mice of the same age were recruited as the control group. Then the modeled KK-Ay mice were divided into 5 groups, i.e., the model group, the Pioglitazone Hydrochloride Tablet treatment group (8 mg/kg, as the positive control group), and the high dose JTXZT group (10 g/kg), the middle dose JTXZT group (5 g/kg), and the low dose JTXZT group (2.5 g/kg), 11 in each group. Eight weeks was taken as one therapeutic course. All medicines were given by gastrogavage. The food intake and body weight were measured every week. The blood glucose level was determined once every 2 weeks. The levels of fasting blood glucose (FBG), serum lipids (TC and TG), insulin (INS), and leptin (Lep) were assayed 8 weeks after medication. The weight of liver and fat were weighed to calculate their indices. Then the adipose denaturalization of the liver was classified. The numbers of the pancreatic islet and adipocytes were respectively counted.</p><p><b>RESULTS</b>Compared with the model group, the food intake and the body weight obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). From the 6th week, the FBG level obviously decreased in the high dose JTXZT group (P < 0.01). After eight successive weeks of intragastric administration, the levels of TG and INS obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). The Lep level somewhat decreased in the high dose JTXZT group (P < 0.05). The indices of the liver and fat obviously decreased and the number of the pancreatic islet obviously increased in the 3 JTXZT groups (P < 0.05, P < 0.01). The number of adipocytes obviously decreased in the high and middle dose JTXZT groups (P < 0.05, P < 0.01). The liver fatty degeneration was obviously improved in the high dose JTXZT group (P < 0.05).</p><p><b>CONCLUSION</b>JTXZT had obvious effects on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with DM obesity.</p>

Serum testosterone reduction and metabolism in aging male rats: correlation and mechanism / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of serum testosterone reduction, its relationship with metabolism, changes in the number and morphology of Leydig cells and endocrine function in aging male rats.</p><p><b>METHODS</b>The levels of serum total testosterone (tT), LH, FSH, HDL, LDL, TG, TC, Glu, INS, IRG and LP were determined in young (9 mo) and aging rats (12, 15, 18 and 21 mo), with 6 in each group. The morphological changes of Leydig cells were observed under the microscope. The concentrations of testosterone secreted from the cultured Leydig cells with the stimulation of hCG and Forskolin were assayed. The apoptosis rates of Leydig cells were detected by TUNEL. The visceral fat was isolated and weighed, and the Lee's index calculated. All the above indexes were recorded and compared among different age groups.</p><p><b>RESULTS</b>The aging rats showed a significant decrease in the levels of serum tT and TSI ([1.26 +/- 0.65] ng/ml and [0.07 +/- 0.65] ng/mIU) as compared with the young rats ([3.24 +/- 0.38] ng/ml and [0.21 +/- 0.01] ng/mIU) (P < 0.01). Obvious differences were found in the morphology of Leydig cells among different age groups. The T secretion of Leydig cells at 24, 48 and 72 h in aging rats was markedly decreased (P < 0.05) while their TUNEL positive rate remarkably increased in the aging rats (17.36% +/- 1.31%) compared with the young ones (7.02% +/- 1.05%) (P < 0.05). There were statistically significant differences between the young and aging rats in all the biochemical parameters including IRG, HDL, LDL, TG, TC and visceral fat content (P < 0.05), except the levels of serum Glu, INS and LP (P > 0.05).</p><p><b>CONCLUSION</b>The serum T level and secreting capacity of Leydig cells are significantly lower in aging rats than in young ones, and the metabolic parameters undergo regular changes with the decreasing level of serum T. The reduction of testosterone in aging male rats may be associated with the decreased secreting capacity and number of Leydig cells and declined function of the pituitary.</p>

Effect of Jiangtang Xiaozhi capsule on morphological changes of islet and liver in rat model corrected of type 2 diabetes corrected mellitus / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of Jiangtang Xiaozhi capsule (JXC) on morphological changes of islets and liver at rat model of type 2 diabetic mellitus and provide the experimental basis for the clinical therapy of type 2 diabetic mellitus.</p><p><b>METHOD</b>Wister rats were fed on a diet enriched in fat and glucose to induce insulin resistan, the rats were injected intrapertoneally with a low-dose streptozotocin (STZ) twice (25 mg x kg(-1)) to induce hyperglycemia, so the successful rat model of type 2 diabetes were established. The experimental rats were divided into model group, high dose JXC group, middle dose JXC group, low dose JXC group, Erjiashuanggua group, Jinqijiangtang group and normal control group. After all the treatment groups received their own medicine for two months, all the rats were sacrificed and morphological examination on their islets and livers were performed.</p><p><b>RESULT</b>Fatty liver in various degrees was seen in the model group and all the treatment groups, but the liver steatosis in middle and low dose JXC groups was significantly milder than that in model group (P < 0.05). Islets in the high dose JXC group were significantly more than that in the model group (P < 0.05).</p><p><b>CONCLUSION</b>JXC can improve significantly the pathological change in islets and liver steatosis at rat model of type 2 diabetic mellitus.</p>