Prevalence, risk factors and clinical correlates of glucose disturbances in a large sample of Han Chinese patients with first-episode drug-naïve major depressive disorder.

Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage.

Protective Effect of Nicorandil on Contrast-Induced Acute Kidney Injury After Emergency Percutaneous Coronary Intervention.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n = 55) and the control group (n = 101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 µmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and ß2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P = .043). Compared with the control group, Scr, uric acid, and ß2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P = .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

Acetylated tau exacerbates learning and memory impairment by disturbing with mitochondrial homeostasis.

Increased tau acetylation at K274 and K281 has been observed in the brains of Alzheimer's disease (AD) patients and animal models, and mitochondrial dysfunction are noticeable and early features of AD. However, the effect of acetylated tau on mitochondria has been unclear until now. Here, we constructed three type of tau forms, acetylated tau mutant by mutating its K274/K281 into Glutamine (TauKQ) to mimic disease-associated lysine acetylation, the non-acetylation tau mutant by mutating its K274/K281 into Arginine (TauKR) and the wild-type human full-length tau (TauWT). By overexpression of these tau forms in vivo and in vitro, we found that, TauKQ induced more severe cognitive deficits with neuronal loss, dendritic plasticity damage and mitochondrial dysfunctions than TauWT. Unlike TauWT induced mitochondria fusion, TauKQ not only induced mitochondria fission by decreasing mitofusion proteins, but also inhibited mitochondrial biogenesis via reduction of PGC-1a/Nrf1/Tfam levels. TauKR had no significant difference in the cognitive and mitochondrial abnormalities compared with TauWT. Treatment with BGP-15 rescued impaired learning and memory by attenuation of mitochondrial dysfunction, neuronal loss and dendritic complexity damage, which caused by TauKQ. Our data suggested that, acetylation at K274/281 was an important post translational modification site for tau neurotoxicity, and BGP-15 is a potential therapeutic drug for AD.

Clinical Characteristics and Outcomes of Chinese Patients with Premature Acute Coronary Syndrome.

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Beneficial effects of high-density lipoprotein (HDL) on stent biocompatibility and the potential value of HDL infusion therapy following percutaneous coronary intervention.

Several epidemiological studies have shown a clear inverse relationship between serum levels of high-density lipoprotein cholesterol (HDL-C) and the risk of atherosclerotic cardiovascular disease (ASCVD), even at low-density lipoprotein cholesterol levels below 70 mg/dL. There is much evidence from basic and clinical studies that higher HDL-C levels are beneficial, whereas lower HDL-C levels are detrimental. Thus, HDL is widely recognized as an essential anti-atherogenic factor that plays a protective role against the development of ASCVD. Percutaneous coronary intervention is an increasingly common treatment choice to improve myocardial perfusion in patients with ASCVD. Although drug-eluting stents have substantially overcome the limitations of conventional bare-metal stents, there are still problems with stent biocompatibility, including delayed re-endothelialization and neoatherosclerosis, which cause stent thrombosis and in-stent restenosis. According to numerous studies, HDL not only protects against the development of atherosclerosis, but also has many anti-inflammatory and vasoprotective properties. Therefore, the use of HDL as a therapeutic target has been met with great interest. Although oral medications have not shown promise, the developed HDL infusions have been tested in clinical trials and have demonstrated viability and reproducibility in increasing the cholesterol efflux capacity and decreasing plasma markers of inflammation. The aim of the present study was to review the effect of HDL on stent biocompatibility in ASCVD patients following implantation and discuss a novel therapeutic direction of HDL infusion therapy that may be a promising candidate as an adjunctive therapy to improve stent biocompatibility following percutaneous coronary intervention.

Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial.

Background Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double-blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST-segment-elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6-mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long-term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no-reflow/slow-flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST-segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion. Conclusions In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.

Valve implantation for successful sealing of a balloon predilatation-induced annular rupture during transcatheter aortic valve replacement.

Annular rupture is a rare and dreaded complication of transcatheter aortic valve replacement (TAVR) and even rarer when caused by predilatation balloon aortic valvuloplasty. This complication often presents as sudden cardiac tamponade with hypotension and requires urgent intervention. The traditional rescue strategy for patients with annular rupture is emergency surgical repair. However, the mortality rate is still high, considering that most patients who undergo TAVR are not candidates for conventional cardiac surgery. Therefore, there is a need for additional emergency treatment strategies to decrease mortality. This report describes a case of predilatation-induced annular rupture during TAVR that was successfully sealed at the rupture site by valve implantation. This case suggests that continuing with valve deployment may be a successful treatment for predilatation-induced annular rupture during TAVR.

Measuring Annual Variation in Reproductive Output Reveals a Key Role of Maternal Body Condition in Determining the Size of Eggs in Snakes.

Long-term studies are especially suited for disentangling the effects of extrinsic and intrinsic factors on both total reproductive investment and reproductive allocation in offspring number versus offspring size. Female reproductive traits of the red-banded wolf snake (Lycodon rufozonatus) from Zhejiang, East China were studied in four years between 1999 and 2014. Egg-laying dates overall extended from late June to late July, and varied among years. Postpartum body mass, clutch size, clutch mass, and egg size were positively related to female size (snout vent length, SVL) in each year. Postpartum body mass, clutch mass, and egg size differed among years after accounting for female SVL, whereas clutch size did not. Setting female SVL at the same level, postpartum body mass was greater in 2010 than in 2014, clutch mass was greater in 2010 than in 2011 and 2014, and egg size was greater in 2010 than in the other three years. Females did not trade off egg size against number. Egg size was positively related to postpartum body condition in each year. Females laid larger eggs in 2010 than in other three years after removing the influence of maternal body condition. Our study provides evidence for the traditional view that reproductive output is highly linked to maternal body size in snakes, but not following Smith and Fretwell's (1974) classic prediction that females with different amounts of resources to invest in reproduction should give priority to adjusting the number rather than size of their offspring. Maternal body size and condition both are important sources of variation in egg size, but factors other than these two variables may also affect the size of eggs produced by female L. rufozonatus.

Metformin promotes microglial cells to facilitate myelin debris clearance and accelerate nerve repairment after spinal cord injury.

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.

Annular and supra-annular structure assessments for transcatheter aortic valve replacement in patients with bicuspid aortic stenosis.

The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes.

The first complete mitochondrial genome of the Grey-bellied Green Ratsnake Gonyosoma frenatum (Gray, 1853) and its phylogenetic placement.

We sequenced the complete 17,209 bp mitochondrial genome (mitogenome) of Gonyosoma frenatum (Squamata: Colubridae) using next-generation sequencing. It consists of 13 PCGs, two ribosomal RNA genes, 22 transfer RNA genes, one non-coding region of an L-strand replication origin, and two control regions. The overall nucleotide composition was 34.7% of A, 24.8% of T, 12.3% of G, and 28.1% of C. The result of the phylogenetic analysis showed that G. frenatum, a member of Colubridae, is sister to other New World and Old World ratsnakes. The new data could help better understand the phylogenetic status of the genus Gonyosoma and the evolutionary history of Colubridae species.

The complete mitochondrial genome of the Chinese mountain keelback (Natricidae: Opisthotropis kuatunensis), comparative and phylogenetic analysis.

Opisthotropis kuatunensis is classified in the family Natricidae and is widespread in southern China. In this study, we sequenced and analyzed the circular mitochondrial genome of O. kuatunensis from the Fujian Province, China. The complete mitogenome is 17,279 bp in length, and includes 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNA, 1 non-coding region of an L-strand replication origin and 2 control regions (D-loop1 and D-loop2). Phylogenetic analysis based on the complete mitochondrial genome supported Opisthotropis as monophyletic and sister to Nerodia and fully resolved O. kuatunensis on a branch with O. latouchii. This study contributes to the systematics, phylogeny and taxonomy of the Natricidae.

Long-term amlodipine-based combination therapy attenuates seasonal variation of blood pressure in hypertensive patients.

Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy.

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

Biology of interleukin-38 and its role in chronic inflammatory diseases.

Interleukin (IL)-38 is the tenth member of the IL-1 cytokine family. IL-38 shares high similarity with IL-36Ra and IL-1Ra and can bind to their receptors, thus exerting an anti-inflammatory effect. Despite the lack of a signal peptide, IL-38 can be released from several cell types, but its maturation process remains obscure. The role of IL-38 in numerous inflammatory diseases, especially in autoimmune diseases, has been extensively studied. In this review, we discuss the characteristics, biological functions and pathways of IL-38, as well as its role in several chronic inflammatory diseases. Better understanding the role of IL-38 will pave the way for clinical treatments in the near future.

Differences in oscillometric blood pressure readings between unsupported and supported back conditions.

Appropriate body posture is important for accurate blood pressure (BP) measurement. However, the impact of an unsupported back on BP readings is currently controversial. This study included 224 subjects (18-86 years old, 54.5 ± 15.5 years old, 105 males). BP was measured with an oscillometric BP device randomly following one of two protocols for back support conditions: (1) supported-unsupported-supported-unsupported, or (2) unsupported-supported-unsupported-supported. The average of the two systolic BP (SBP) and diastolic BP (DBP) readings in the same position was recorded as the final BP value. The differences in BP between the unsupported and supported back conditions were calculated as delta BP. Moreover, the percentage variation in BP (PV) was calculated with the formula delta BP/BP with an unsupported back. Multivariable regression analysis evaluated the impact of age, sex, hypertension history and supported BP level on PV. The SBP/DBP levels measured with an unsupported back were slightly higher than those when the back was supported (132.7 ± 19.5/79.6 ± 12.9 mmHg vs. 130.3 ± 20.0/78.5 ± 14.3 mmHg), and the delta SBP (2.3 mmHg) was statistically significant. The multivariable regression analysis showed that age was a positive factor but supported SBP level as a negative factor for systolic PV, while age and supported DBP level were positive factors, but hypertension history was a negative factor for diastolic PV. For a group participant, the mean difference in oscillometric SBP/DBP in the unsupported back position was 2.3/1.0 mmHg higher than that in the supported back position.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy.

As a primary cause of dementia and death in older people, Alzheimer's disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy-lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.

Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury.

The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 µg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 µM H2O2. At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and ß-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018.