1.Effect of high-frequency stimulation to subthalamic nucleus on STR neuronal firing rates in Parkinson disease rats.
Pei-Fei GU ; Dong-Ming GAO ; Yu SHANG
Chinese Journal of Applied Physiology 2004;20(1):83-87
AIMTo observe the change of STR neuronal firing rates with high frequency stimulation of subthalamic nucleus in PD rats.
METHODSA model of Parkinson's disease was induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequency stimulation to STN, the spontaneous firing rates of STR on normal and PD rats were recorded by using extracellular recordings.
RESULTSStimulation caused a direct excited effect of STR neurons in normal rats whereas a excited and inhibited effect in PD rats. The inhibited effect was correlated with the stimulation period (r = 0.94).
CONCLUSIONStimulation to STN may inhibit the spontaneous firing rates of STR neurons in PD rats. These results also give some clues that high-frequency stimulation to STN may be a effective therapy to the clinical treatment of Parkinson's disease.
Action Potentials ; Animals ; Corpus Striatum ; physiopathology ; Disease Models, Animal ; Electric Stimulation Therapy ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus
2.Quantitative evaluation of “dual channel”management policy of national medical insurance negotiation drugs based on PMC index model
China Pharmacy 2024;35(19):2335-2339
OBJECTIVE To quantitatively evaluate the “dual channel” management policy of national medical insurance negotiation drugs at the provincial level, analyze the shortcomings and excellent experience and provide reference for the optimization of the policy. METHODS Taking the “double-channel” management policy of national medical insurance negotiation drugs in 31 provinces as the research object, text mining method was used to summarize the key contents of the policy; the policy modeling consistency (PMC) index model is constructed, and the “dual channel” management policies of 31 provinces are quantitatively analyzed through the evaluation model. Taking Beijing and Chongqing as examples, the differences between good policies and acceptable policies are compared. RESULTS Among the 31 provinces, the PMC index of 18 provinces is between 6.00 and <8.00, which belongs to the excellent policies. The PMC index of 13 provinces is between 4.00 and <6.00, which belongs to acceptable policies. The policies of Beijing and Chongqing are consistent in 5 aspects, such as policy nature and policy effectiveness, while there are differences in 4 aspects, such as policy content and policy audience. CONCLUSION The “dual channel” management policies in most provinces are at a relatively perfect level, and some provinces need to continuously optimize the policy design and improve the policy rules according to the actual situation of their own medical and health development; establish the management mode of designated pharmacies, clarify the selection rules and exit mechanism; pay attention to the construction of pharmaceutical care, and promote the outflow of prescriptions.
3.Intranasal absorption of rivastigmine hydrogen tartrate and brain targeting evaluation
Hui-min WANG ; Guo-guang WEI ; Ming-yue GAO ; Xiang-qin GU ; Shi-rui MAO
Acta Pharmaceutica Sinica 2016;51(10):1616-
To investigate factors influencing the intranasal absorption of rivastigmine hydrogen tartrate (RHT), we studied the pharmacokinetics of RHT after intranasal administration and evaluated its brain targeting behavior. In situ rat nasal perfusion model was used in the study and pH impact was examined on the intranasal absorption of RHT. High performance liquid chromatography (HPLC) method was established to measure RHT concentration in the plasma and brain tissue after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting index (DTI), and nose-to-brain direct transport percentage (DTP) were calculated. It was demonstrated that the intranasal absorption mechanism of RHT was passive diffusion. The absorption rate was highest at pH 6.0. The absolute bioavailability of intranasally administrated RHT was 73.58%. Compared with that of intravenous administration, RHT absorption into the brain was faster and more efficient after intranasal delivery, and the DTI value was 195.27% of intravenous injection. Moreover, 48.79% of the drug can be absorbed directly from the nose into the brain without systematic circulation. Meanwhile, drug elimination half-time in the brain was prolonged by 1.4 fold compared to that of intravenous injection. In conclusion, intranasal administration of RHT not only improves drug absorption into the system, but also enhances drug absorption rate and content in the brain remarkably, which is an advantage in the treatment of central nervous system-related diseases.
4.Mechanism of Osteosarcopenia and Its Control by Exercise
Dan JIN ; Xin-Yu DAI ; Miao LIU ; Xue-Jie YI ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(5):1105-1118
Osteosarcopenia (OS) is a multifactorial, multiaetiologic degenerative metabolic syndrome in which sarcopenia coexists with osteoporosis, and its influences are related to aging-induced mechanics, genetics, inflammatory factors, endocrine disorders, and irregular lifestyles. With the accelerated aging process in our country, osteosarcopenia has become a public health problem that cannot be ignored, with a higher risk of falls, fractures, impaired mobility and death. In recent years, scholars at home and abroad have conducted a lot of research on osteosarcopenia, but their pathogenesis is still unclear. Understanding the signaling pathways associated with osteosarcopenia is of great significance for further research on the pathogenesis of these disorders and for finding new targets for treatment. Studies have shown that activation of the PI3K/Akt signaling pathway promotes osteoblast differentiation as well as skeletal muscle regeneration, indicating that inhibition of thePI3K/Akt signaling pathway is closely related to the development of osteosarcopenia. Muscle factor-mechanical stress interactions can maintain osteoblast viability by activating the Wnt/β-catenin signaling pathway, suggesting that Wnt signaling is important in muscle and bone crosstalk. The Notch signaling pathway also plays an important role in improving bone and muscle mass and function, but different researchers hold different views, which need to be further validated and refined in subsequent studies. Exercise, as an existing non-pharmacological treatment with strong and sustained effects on physical function and muscle strength, also significantly increases bone density in osteoporosis patients, which may be mainly due to the fact that exercise induces changes in the form and function of bones, in the form of muscular pulling and indirectly improves the bone mass, and changes in the bone strength can also change the number, shape as well as the function of the muscles. At the same time, the mechanism of different exercise modalities focuses on different aspects, and there are differences in exercise time, exercise intensity, and therapeutic effects in the implementation of interventions. Aerobic exercise can improve the quality of skeletal muscle and increase the expression of osteogenesis-related genes by stimulating mitochondrial biosynthesis, as well as improve the quality and strength of bones and muscles through the Wnt/β- catenin and PI3K/Akt signaling pathways, effectively preventing and controlling the occurrence of musculoskeletal disorders. High-intensity resistance exercise has a significant effect on improving the quality of muscles and bone mineral density, but older people with osteosarcopenia suffer from a decline in muscle quality and strength, and a decline in bone mineral density, which makes them very susceptible to fracture, so they should select the intensity of the training in a gradual and orderly manner, from small to large. What kind of exercise intensity and exercise modalities are most effective in improving the occurrence and development of osteosarcopenia needs to be further investigated. Therefore, this paper mainly reviews the epidemiology of osteosarcopenia, diagnostic criteria, the related signaling pathways (PI3K/Akt pathway, Wnt/β-catenin pathway, Notch pathway, NF-κB pathway) that jointly regulate the metabolic process of myocytes and skeletal cells, as well as the interventional effects of different exercise modes on osteosarcopenia, with the aim of providing theoretical bases for the clinical treatment of osteosarcopenia, as well as enhancing the preventive capacity of the disease in old age.
5.Research progress on the mechanism of silibinin in preventing and treating diabetes and its complications
Mengqiu LIANG ; Lei LI ; Yanqiu MENG ; Haifeng WANG ; Zhipeng ZHANG ; Guozhu GAO
China Pharmacy 2023;34(7):887-891
Silibinin is a kind of flavonoid extracted from the dried ripe fruit of Silybum marianum,a plant of compositae. It has a variety of pharmacological activities and can effectively prevent and treat diabetes and its complications. This paper reviews the research progress on the mechanism of silibinin in the prevention and treatment of diabetes and its complications. It is found that silibinin can prevent and treat diabetes by up-regulating the expression of estrogen receptor-α,activating the duodenum-brain-liver axis pathway and stabilizing the protein structure. It can prevent and cure the nervous system diseases of diabetes by activating glucagon-like peptide-1 receptor/protein kinase A signal pathway and inhibiting the hyperphosphorylation of tau protein. It can prevent and treat diabetic retinopathy by down-regulating the expression and activity of pro-inflammatory,pro-oxidative factors and histone deacetylase 6. It can prevent diabetic nephropathy by activating protein kinase B signal pathway and reducing the level of transforming growth factor-β1,and prevent and treat diabete’s obesity by inhibition of hepatobiliary transporter CD36 expression, and suppressing nuclear factor-κB pathway and its downstream expression of pro-inflammatory cytokines(tumor necrosis factor-α and interleukin-1β),etc.
6.The Role and Possible Mechanisms of Exercise in Combating Osteoporosis by Modulating The Bone Autophagy Pathway
Xin-Yu DAI ; Bin LI ; Dan JIN ; Xue-Jie YI ; Rui-Qi HUANG ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(7):1589-1603
Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.
7.Modification of in situ perfusion in study of nasal absorption of insulin
Ming-yue GAO ; Ying-nan HUO ; Xin SHEN ; Shi-rui MAO
Acta Pharmaceutica Sinica 2018;53(9):1551-1556
The objective of this study is to develop an in vitro screening method for nasal absorption of insulin. First, the adaptability of in situ rat nasal perfusion test for the study of insulin was investigated. It was found that insulin was liable to be absorbed on the silicone tube and the traditional method is not suitable. However, addition of 0.001% Labrasol into the perfusate can effectively solve this problem. A modified method suitable for in situ rat nasal perfusion of insulin was established with the addition of 0.001% Labrasol into the perfusate. Using the modified method, effect of pH and drug concentration on the absorption of insulin in the nasal cavity was further investigated. The results suggest that compared with pH 4.5 and pH 7.4, the drug absorption rate was the lowest at pH 6.0. The intranasal absorption mechanism of insulin may be passive diffusion.
8.Simultaneous quantitative analyses of eight components in Artemisia capillaris Thunb standard decoction based on a quantitative method of multi-components with a single-marker
Ying ZHANG ; Hua-rong XU ; Jun-shan LI ; Han GAO ; Kai-shun BI ; Qing LI
Acta Pharmaceutica Sinica 2019;54(9):1661-1666
A quantitative analytical method for multi-components with a single-marker (QAMS) was established for simultaneous determination of neochlorogenic acid, chlorogenic acid, caffeic acid, cryptochlorogenic acid, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid in
9.Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted
Shi-te GAO ; Zhen-yu KUAI ; Zhi-peng ZHANG ; Yan-qiu MENG
Acta Pharmaceutica Sinica 2023;57(3):721-728
By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The
10.Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with Soluplus
Hang SONG ; Li-fang GAO ; Qiang FU ; Jue WANG ; Zhong-gui HE
Acta Pharmaceutica Sinica 2019;54(1):14-21
Spironolactone, a class II drug of the biopharmaceutics classification system, has low oral bioavailability due to poor solubility. Spironolactone solid dispersions were prepared using the solvent method in order to improve its aqueous solubility. Optimization studies of spironolactone solid dispersions were performed using