Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.

Catgut implantation at acupoints increases the expression of glutamate aspartate transporter and glial glutamate transporter-1 in the brain of rats with spasticity after stroke

Catgut implantation at acupoints has been shown to alleviate spasticity after stroke in rats.However,the underlying mechanisms are poorly understood.In this study,we used the rat middle cerebral artery occlusion model of stroke.Three days after surgery,absorbable surgical catgut sutures were implanted at Dazhui（GV14）,Jizhong（GV6）,Houhui,Guanyuan（CV4）and Zhongwan（CV12）.The Zea Longa score was used to assess neurological function.The Modified Ashworth Scale was used to evaluate muscle tension.The 2,3,5-triphenyl-tetrazolium chloride assay was used to measure infarct volume.Immunohistochemical staining was performed for glutamate aspartate transporter（GLAST）and glial glutamate transporter-1（GLT-1）expression.Western blot assay was used to analyze the expression of GLAST and GLT-1.Reverse transcription and polymerase chain reaction were carried out to assess the expression of GLAST and GLT-1m RNAs.After catgut implantation at the acupoints,neurological function was substantially improved,muscle tension was decreased,and infarct volume was reduced in rats with spasticity after stroke.Furthermore,the expression of GLAST and GLT-1 m RNAs was increased on the injured（left）side.Our findings demonstrate that catgut implantation at acupoints alleviates spasticity after stroke,likely by increasing the expression of GLAST and GLT-1.

miRNA-103: Molecular link between insulin resistance and nonalcoholic fatty liver disease

AIM: To investigate the associations between miRNA-103(mi R-103) and insulin resistance and nonalcoholic fatty liver disease(NAFLD).METHODS: Serum samples were collected from 50 NAFLD patients who were overweight or obese(NAFLD group) and from 30 healthy subjects who served as controls(normal control group). Quantitative polymerasechain reaction was used to detect expression of mi R-103. Fasting plasma glucose, fasting insulin, and triglyceride(TG) levels were measured. Homeostasis model assessment was used to evaluate basal insulin resistance(HOMA-IR). Patient height and weight were measured to calculate body mass index(BMI).RESULTS: Compared with the normal control group, higher serum levels of mi R-103 were expressed in the NAFLD group(8.18 ± 0.73 vs 4.23 ± 0.81, P = 0.000). When P = 0.01(bilateral), mi R-103 was positively correlated with HOMA-IR(r = 0.881), TG(r = 0.774) and BMI(r = 0.878), respectively. mi R-103, TG and BMI were all independent factors for HOMAIR(β = 0.438/0.657/0.251, P = 0.000/0.007/0.001). mi R-103, TG, BMI and HOMA-IR were all risk factors for NAFLD(odds ratio = 2.411/16.196/1.574/19.11, P = 0.009/0.022/0.01/0.014).CONCLUSION: mi R-103 is involved in insulin resistance and NAFLD, and may be a molecular link between insulin resistance and NAFLD and a therapeutic target for these disorders.

Abnormal Local Activity and Functional Dysconnectivity in Patients with Schizophrenia Having Auditory Verbal Hallucinations

Auditory verbal hallucination(AVH)is emphasized as a pathological hallmark of schizophrenia.Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks.However,no clear conclusion has still been reached.This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity(LA)and functional connectivity(FC)insights,while excluding confounding factors from other positive symptoms.A total of 42 patients with AVH(AVH patients group,APG),26 without AVH(non-AVH patients group,NPG),and 82 normal controls(NC)underwent resting-state functional magnetic resonance imaging(fMRI).LA measures,including regional homogeneity(ReHo)and fractional amplitude of low-frequency fluctuations(fALFF),and FC measures were evaluated to understand the neuroimaging mechanism of AVH.APG showed increased ReHo and fALFF in the bilateral putamen(Put)compared with NPG and NC.FC analysis(using bilateral putamen as seeds)revealed that all patients showed abnormal FC of multiple resting state network regions,including the anterior and post cingulate cortex,middle frontal gyrus,inferior parietal gyrus,and left angular gyrus.Interestingly,APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC.The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH,providing evidence for the functional disconnection hypothesis of schizophrenia.

Correlation of visceral adipose tissue content with insulin signal transduction, lipid metabolism features and adipocytokine secretion in patients with T2DM

Objective: To study the correlation of visceral adipose tissue content with insulin signal transduction, lipid metabolism features and adipocytokine secretion in patients with type 2 diabetes mellitus (T2DM). Methods: The patients who were first diagnosed as T2DM in our hospital between March 2015 and February 2018 were selected as the T2DM group, and the healthy subjects who underwent physical examination during the same period were selected as the control group. The T2DM group underwent visceral adipose tissue content scanning and were divided into those with VAT 100 cm2 and those with VAT<100 cm2. Fasting peripheral blood was collected from the two groups to measure the F-Ins, lipid metabolism indexes and adipocytokines and calculate the HOMA-IR and ISI. Results: F-Ins and HOMA-IR levels as well as LDL-C, Apo-B, FFA, LP and RBP4 contents of T2DM group were significantly higher than those of control group whereas ISI level as well as HDL-C, Apo-A, APN and Omentin-1 contents was significantly lower than those of control group;F-Ins and HOMA-IR levels as well as of LDL-C, Apo-B, FFA, LP and RBP4 contents of T2DM group of patients with VAT 100 cm2 were higher than those of patients with VAT<100 cm2 whereas ISI level as well as HDL-C, Apo-A, APN and Omentin-1 contents was lower than those of patients with VAT<100 cm2. Conclusion: The increase of visceral adipose tissue content in patients with T2DM can aggravate the insulin resistance and cause the disorder of lipid metabolism and adipocytokine secretion.

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations： A Resting-state Functional Magnetic Resonance Imaging Study

Background： Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination （AH）. However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods： Auditory hallucinated patients group （n = 42 APG）, no hallucinated patients group （n = 42 NPG） and normal controls （n = 84 NCs） were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index （degree centrality [DC]） across the entire brain networks was calculated and evaluated among three groups. Results： DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG. the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion： Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.

Biological Function and Mechanism of Long Noncoding RNAs Nuclear-Enriched Abundant Transcript I in Development of Cervical Cancer

Background： Accumulating documents have demonstrated that long noncoding RNAs （lncRNAs） play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 （NEAT1） has been identified to be involved in the progression of many types of cancers. However, the biological function of NE.4T1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEATI in cervical cancer progression. Methods： Quantitative real-time polymerase chain reaction （qRT-PCR） was utilized to identify the expression of lncRNA NE,4 T1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NE,4T1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway. Results： High expression of NE,4T1 predicted poor prognosis of cervical cancer patients （χ^2= 0.735, P = 0.005）. Knockdown of NE,4T1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 （t = -18.76, P = 0.003） and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 （t = -5.54, P = 0.031）. However, overexpression of NEA T1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 （t = 7.27, P = 0.018）. Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 （t = -8.08, P = 0.015） and reduced the migratory number in HeLa cell from 123.667± 12.097 to 67.667 ± 7.095 （t = -6.03, P = 0.026）. Overexpression of NEAT1 increased the migratory number of SiHa cell from 127.333 ±16.042 to 231.333 ±31.786 （t = 4.92, P = 0.039）. Conclusion： NEAT1 may exert oncogenic function in cervical cancer and serve as a novel therapeutic target for cervical cancer.

Tonifying Shen-Yin and-Yang Principles in Treating Osteoporosis: All Roads Lead to Rome

Tonifying Shen strategy works as an important alternative and complementary method that is widely used to treat osteoporosis in Traditional Chinese Medicine(TCM) based on the proper identification of Zheng. Shen deficiency Zheng is one of the main types of osteoporosis while Shen-Yin and-Yang deficiencies represent two basic principles/types of Shen deficiency. Currently, Tonifying Shen strategy, in particular, the Tonifying Shen-Yin and-Yang principles, has been demonstrated to exert osteoprotective effects. However, the mechanisms by which Tonifying Shen strategy and/or Tonifying Shen-Yin and-Yang principles function in treating osteoporosis are still not clearly understood. Here we first briefly explore current understanding of Tonifying Shen strategy, such as Tonifying Shen prescriptions, herbs, and effective components, in treating osteoporosis. Furthermore, the mechanism of Tonifying Shen-Yang principle in treating osteoporosis is reviewed from the clinic experience, animal, and mechanistic investigation. Moreover, the mechanisms by which Tonifying Shen-Yin principle in treating osteoporosis are established. Finally, we compare the similarity and difference between Tonifying Shen-Yang and-Yin principles in treating osteoporosis.Our findings indicate that both principles exert bone-protective effects in treating osteoporosis by simultaneously stimulating the differentiation of mesenchymal stem cells(MSCs) into osteoblast and the differentiation of hematopoietic stem cells(HSCs) into osteoclast. However,Tonifying Shen-Yin principle is in favor of increasing bone mineral density(BMD) while Tonifying Shen-Yang principle is in favor of osteoporosis-related syndromes. Our findings indicate that Tonifying Shen-Yin and-Yang principles not only share some similarity but also obtain some difference in treating osteoporosis.

Role of adult resident renal progenitor cells in tubular repair after acute kidney injury

Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the fi eld of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells（ARPCs） on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms rela ted to ARPC activation and modulation, as well as the challenges that remain to be faced.