RESUMO
Diabetic peripheral neuropathy(DPN) is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage, which is characterized by axonal degenerative necrosis, Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features, this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently, the pathogenesis of DPN may be related to oxidative stress, inflammatory response, metabolic abnormality, and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose, nourishing nerves and improving microcirculation, which can only alleviate the clinical symptoms of patients, and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria, including mitochondrial biogenesis, mitochondrial dynamics, mitochondrial oxidative stress and mitochondrial autophagy, and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature, it was found that traditional Chinese medicine(TCM) can improve the low level of mitochondrial biogenesis in DPN, maintain the balance of mitochondrial dynamics, inhibit mitochondrial oxidative stress and mitochondrial autophagy, and delay apoptosis of Schwann cells and neural axon damage, which has obvious effects on the treatment of DPN. With the deepening of research, mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs, therefore, this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control, with the aim of providing a theoretical research basis for the discovery of new drugs.
RESUMO
Objective Exploring the effect of Tong luo tang tai(TLTT)on diabetic peripheral neuropathy(DPN)in GK rats with Wnt/β-The influence of the catenin signaling pathway.Methods Fifty GK rats were randomly divided into model group,TLTT high,medium,and low dose groups,and Western medicine group,with 10 rats in each group.Another 10 wistar rats were selected as the normal group.Except for the normal group,all other groups were fed with high fat to prepare DPN rat models.After 15 weeks,the DPN model was successfully prepared,and the rats in each group were treated by gavage.The high,medium,and low dose groups of TLTT were given traditional Chinese medicine TLTT 28 g·kg-1,14 g·kg-1,and 7 g·kg-1,respectively.The western medicine group was given metformin 100 mg·kg-1 and mecobalamin 0.2 mg·kg-1 by gavage.Rats in each group were administered once a day for 8 consecutive weeks.The general state,fasting blood sugar(FBS),thermal contraction latency(TWL),motor nerve conduction velocity(MNCV),and pathological changes in the sciatic nerve tissue were observed under transmission electron microscopy(Real time PCR)Western blot detection of wingless MMTV integration site family member 3A(Wnt3a)β Catenin(β-Catenin,Glycogen Synthesis Kinase-3β Glycogen synthesis kinase-3β,GSK-3β)MRNA and protein expression levels of antagonists(WNT inhibitor factor-1,Wif-1)on the Wnt signaling pathway.Results Compared with the normal group,the model group showed poorer general condition and significant pathological ultrastructural changes in the sciatic nerve.Its FBS level increased(P<0.01),TWL level decreased(P<0.01),and MNCV significantly slowed down(P<0.01).The model group had Wnt3a β-Catenin,GSK-3β MRNA and protein expression levels decreased(P<0.05),while Wif-1 mRNA and protein expression levels increased(P<0.01).After drug intervention,compared with the model group,the general condition and pathological ultrastructure of the sciatic nerve were improved in the TLTT high,medium,low,dose,and Western medicine groups,with a decrease in FBS levels(P<0.01)and an increase in TWL levels(P<0.05).The MNCV of each TLTT dose group and Western medicine group was significantly improved(P<0.01).The Wnt3amRNA of the TLTT high-dose group and Western medicine group was significantly increased(P<0.05),while the Wif-1mRNA of the TLTT high-dose group and Western medicine group was significantly reduced(P<0.05),There was a significant increase in Wnt3 protein in the high-dose and Western medicine groups of TLTT(P<0.01),as well as in the high-dose,medium,and low-dose TLTT and western medicine groups β-Catenin protein significantly increased(P<0.01,P<0.05),with high,medium,and low doses of TLTT and Western medicine group GSK-3β The protein significantly increased(P<0.01,P<0.05),while the Wif-1 protein significantly decreased(P<0.01,P<0.05)in the high and medium dose TTLTT and western medicine groups.Conclusion Tongluo Tangtai can alleviate sciatic nerve injury in DPN to a certain extent,and its mechanism may be related to the activation of Wnt/β,the catenin signaling pathway is involved.
RESUMO
Diabetic peripheral neuropathy (DPN) is characterized by insidious onset, easy misdiagnosis, and progression to severe consequences such as diabetic foot ulcers, gangrene, and amputation. The main pathological features of DPN are nerve cell injuries, such as axonal degeneration and necrosis, segmental demyelination of nerve fibers, and apoptosis of Schwann cells. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is a classical pathway that communicates intracellular and extracellular information and regulates biological activities such as cell proliferation, differentiation, apoptosis, autophagy, and migration. It widely affects various cells related to DPN. In recent years, numerous studies have found that the sustained high glucose environment causes abnormalities in the PI3K/Akt signaling pathway. This, in turn, accelerates the occurrence and development of DPN by participating in the pathogenesis of DPN, such as glucose and lipid metabolism, oxidative stress, inflammation, autophagy, apoptosis, and angiogenesis. Therefore, regulating the PI3K/Akt signaling pathway is crucial for the treatment of DPN. Currently, there is a lack of effective measures to slow down or reverse DPN in clinical practice. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating DPN with multiple targets, effects, and components. A large number of animal and clinical studies of TCM treatment of DPN have shown that the PI3K/Akt signaling pathway is an important target for TCM treatment of DPN. Regulating the PI3K/Akt signaling pathway can promote myelin sheath repair and regeneration, delay the process of nerve cell death, and play a role in preventing and treating DPN. However, there is currently no systematic review and summary of this field in China and abroad. Therefore, this article summarized the regulation of the PI3K/Akt signaling pathway and its role in the pathogenesis of DPN, as well as the intervention of effective components of single Chinese medicine or compounds on the PI3K/Akt signaling pathway. This study is expected to provide a reference for the clinical diagnosis and treatment of DPN with TCM, basic research, and drug development.
RESUMO
OBJECTIVE@#To investigate the protective effects of dexmedetomidine (DEX) against cerebral ischemia/reperfusion (I/R) injury in mice and its relation with mitochondrial fusion and fission.@*METHODS@#Male ICR mice were randomly divided into sham-operated group, I/R group, I/R+DEX group and I/R+DEX+dorsomorphin group. Mouse models of cerebral I/R injury were established by modified thread occlusion of the middle cerebral artery. DEX (50 μg/kg) was injected intraperitoneally at 30 min before cerebral ischemia, which lasted for 1 h followed by reperfusion for 24 h. The neurobehavioral deficits of the mice were evaluated based on Longa's scores. The volume of cerebral infarction was detected by TTC staining. The changes in mitochondrial morphology of the brain cells were observed with transmission electron microscopy. Western blotting was performed to detect the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), mitochondrial fusion protein (Mfn2) and mitochondrial fission protein (p-Drp1) in the brain tissues.@*RESULTS@#DEX pretreatment significantly reduced the neurobehavioral score and the percent volume of cerebral infarction in mice with cerebral I/R injury. Treatment with dorsomorphin (an AMPK inhibitor) in addition to DEX significantly increased the neurobehavioral score and the percent volume of cerebral infarction in the mouse models. Transmission electron microscopy showed that DEX obviously reduced mitochondrial damage caused by cerebral I/R injury and restored mitochondrial morphology of the brain cells, and such effects were abolished by dorsomorphin treatment. Western blotting showed that DEX pretreatment significantly increased the expressions of p-AMPK and Mfn2 protein and decreased the expression of p-Drp1 protein in the brain tissue of the mice, and these changes were also reversed by dorsomorphin treatment.@*CONCLUSIONS@#Preconditioning with DEX produces protective effects against cerebral I/R injury in mice possibly by activating AMPK signaling to regulate mitochondrial fusion and fission in the brain cells.
Assuntos
Animais , Masculino , Camundongos , Isquemia Encefálica , Dexmedetomidina , Camundongos Endogâmicos ICR , Dinâmica Mitocondrial , Traumatismo por ReperfusãoRESUMO
Objective:To investigate fathers′ knowledge, attitude and practice of breastfeeding and to analyze the related factors.Methods:From August 2018 to April 2019, 200 fathers of newborns in a Shanghai tertiary obstetrics and gynaecology hospital were surveyed about their breastfeeding knowledge, attitude and practice by convenient sampling and self-designed questionnaires.Results:The average knowledge score was 9.80±2.61, the attitude score was 38.71±4.45, the behavioral score was 39.72±6.48. Multiple linear regression results showed that parents′ education level and the wives′ delivery times were the main factors affecting breastfeeding knowledge score ( t values were 2.016, 2.068, 2.988, P < 0.05). The fathers′ knowledge score and the wives′ delivery method were the main factors affecting attitude score ( t values were -3.029,5.225, P < 0.05). Attitude score and infants′ age stage were the main factors affecting behavior score ( t values were 1.985, 2.633, P<0.05). Conclusion:Fathers′ breastfeeding attitude was positive, but they still had wrong perceptions. There were many deficiencies in breastfeeding related behaviors of fathers. It is necessary for hospitals, communities or other relevant institutions to educate fathers with knowledge related to breastfeeding, to encourage fathers to pay more attention to breastfeeding and urge fathers′ behavior improvement, so as to increase the rate of breastfeeding and promote the health of mothers and infants.
RESUMO
Presepsin(sCD14-ST), is an soluble leukocyte differentiation antigen 14 subtype. It is a glycoprotein fragment and a marker of acute phase reaction. For diagnosis of adult sepsis, bacteremia and bacterial DNAaemia, the area under of ROC is 0.88,0.78 and 0.79, respectively. The levels of Presepsin increase earlier than procalcitonin, and have better clinical value for early diagnosis of sepsis. It is significantly correlated with disease severity and can be used to predict prognosis. One study mentioned that in the absence of organ dysfunction, the value was 235.0 (172.0-340.3) pg/ml, and for one, two, three or more organ dysfunction, were 403.5 (275.8-587.3) pg / ml, 844.5 (559.8-1259.5) pg / ml, 1412.5 (893.0-2675.8) pg/ml (P<0.01), respectively. Another study mentioned that Presepsin is an independent risk factor for 30-day death of sepsis, and it is effective to evaluate poor prognosis with a threshold of >927.5 pg/ml. Presepsin also has clinical value for neonatal and child sepsis. The Greece meta-analysis showed that the AUC for neonatal sepsis diagnosis was 0.9751, which was higher and more sensitive than that of CRP and procalcitonin. Turkish study on children showed a significant increase in sCD14-ST in sepsis patients compared with healthy controls. Its AUC was 0.98, the best threshold was 990 pg/ml. The reference range of this value was been studied, showing that 75% and 95% percentiles of full-term infants are 791 and 1178 pg/ml. Adults do not exceed 200 pg/ml of all age groups. It is affected by renal function. Prospective trials are expected to further clarify its diagnostic value, more therapeutic research to elaborate its therapeutic value, and corresponding clinical practice guideline.