Polyphyllin I alleviates neuroinflammation after cerebral ischemia-reperfusion injury via facilitating autophagy-mediated M2 microglial polarization.

Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia-reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia-reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia-reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

Smart Manufacturing Processes of Low-Tortuous Structures for High-Rate Electrochemical Energy Storage Devices.

To maximize the performance of energy storage systems more effectively, modern batteries/supercapacitors not only require high energy density but also need to be fully recharged within a short time or capable of high-power discharge for electric vehicles and power applications. Thus, how to improve the rate capability of batteries or supercapacitors is a very important direction of research and engineering. Making low-tortuous structures is an efficient means to boost power density without replacing materials or sacrificing energy density. In recent years, numerous manufacturing methods have been developed to prepare low-tortuous configurations for fast ion transportation, leading to impressive high-rate electrochemical performance. This review paper summarizes several smart manufacturing processes for making well-aligned 3D microstructures for batteries and supercapacitors. These techniques can also be adopted in other advanced fields that require sophisticated structural control to achieve superior properties.

Spinocerebellar ataxia type 28 in a Chinese pedigree: A case report and literature review.

RATIONALE: Spinocerebellar ataxia (SCA) is a common neurogenetic disease that mainly manifests as ataxia of posture, gait, and limbs, cerebellar dysarthria, and cerebellar and supranuclear eye movement disorders. SCA has been found to include many subtypes, which are mainly mapped to 2 genetic patterns: autosomal dominant cerebellar ataxia and autosomal recessive cerebellar ataxia. Molecular genetic diagnosis functions as a necessity in its clinical diagnosis and treatment. In preliminary clinical work, we identified a family of SCA28 with rare gene mutation. PATIENT CONCERNS: There are 5 patients in this family. The proband is a 32 year-old male, he mainly manifest unsteady steps for more than 7 months. The daughter of his younger maternal uncle gradually had unsteady steps and unclear speech for 5 years. The proband's mother, uncle and grandfather had similar symptoms, but they all died. DIAGNOSIS: After Brain magnetic resonance imaging, whole exome sequencing and Sanger validation, the patients presented a c.1852A > G missense mutation in the exon region of AFG3L2 gene. The other family members revealed no AFG3L2 mutations. SCA28 is the one uniquely caused by a pathogenic variation in the mitochondrial protein AFG3L2. Combined with the clinical manifestations, auxiliary examinations and sequencing results of the patients (III-3 and III-5), the diagnosis of SCA28 was suspected. INTERVENTIONS: The patients did not receive any drug treatment and the proband receive rehabilitation treatment. OUTCOMES: The symptoms of ataxia were still progressively aggravated. LESSONS: Molecular genetic diagnosis is necessary for ataxia. We here report the case and review the literature.

Identification of p.Arg205Cys in CASR in an autosomal dominant hypocalcaemia type 1 pedigree: A case report.

RATIONALE: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium. PATIENT CONCERNS: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family. DIAGNOSIS: The patient was diagnosed with ADH1 clinically and genetically. INTERVENTIONS: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient. OUTCOMES: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved. LESSONS: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.

Morphological study of safe fixation region of temporomandibular joint prosthesis in Chinese northeast population with 3-dimensional computed tomographic image.

This study aimed to measure temporomandibular joint (TMJ) with 3-dimensional (3D) reconstruction technique in Chinese northeast population, and to clarify the region for fixation and to provide morphological basis for the application of TMJ prosthesis in Chinese setting.Computed tomography (CT) scan and 3D reconstruction were performed with 132 individuals. Structural markers and measurements were further performed with a 3D model of the total TMJ, including the width, thickness and angle of zygomatic arch, the width and height of articular fossa, as well as the area, width, thickness and angle of mandible in the fixation region of the TMJ prosthesis. All the measured indicators values were compared between bilateral sides and gender groups.There was no statistical difference in the measured indicators between the left side and the right side (P > .05). However, certain parameters, including S, L5, L7, P4, and P5, were significantly different among males and females (P < .05).In this study, 3D CT image was used to obtain the measurement data of TMJ, which provided data support for the clinical application of TMJ prosthesis in Chinese population.

Long non-coding RNA Mirt2 prevents TNF-α-triggered inflammation via the repression of microRNA-101.

Parkinson's disease is normally accompanied by excessive inflammation. Myocardial infraction associated transcript 2 (Mirt2) has an activity to relieve inflammation in numerous cell types. Here, we aimed to investigate whether Mirt2 could elevate the resistance of SH-Sy5y cells to inflammation. Tumor necrosis factor alpha (TNF-α) was used to induce inflammation in SH-Sy5y cells. Mirt2 overexpressed or silenced cells were established. MicroRNA-101 (miR-101) mimic was used to up-regulate miR-101. Viable and apoptotic cells as well as reactive oxidative species (ROS) were detected after staining. Proteins associated with apoptosis, interleukin (IL) and signaling regulators were evaluated by Western blot. IL secretion was assessed by ELISA. Mirt2 and miR-101 were determined by qRT-PCR. We discovered that TNF-α weakened viability of SH-Sy5y cells and resulted in sensitivity to apoptosis with cleavage of PARP and caspase-3. Expression and secretion of IL-6 as well as generation of ROS were facilitated by TNF-α. However, Mirt2 overexpression moderated TNF-α-caused apoptosis associated with inflammation and oxidative stress. Mirt2 suppressed TNF-α-induced accumulation of miR-101, and based on this Mirt2 exhibited anti-inflammatory roles. Additionally, TNF-α-triggered phosphorylation of regulators was blocked by Mirt2 while restored by miR-101 mimic. In short Mirt2 overexpression exhibited anti-inflammatory properties through miR-101 suppression. Through down-regulating miR-101, Mirt2 blocked TNF-α-triggered NF-κB/p38MAPK pathway.

Photothermal effects of NaYF4:Yb,Er@PE3@Fe3O4 superparamagnetic nanoprobes in the treatment of melanoma.

Objective: The study aimed to synthesize superparamagnetic NaYF4:Yb,Er@PE3@Fe3O4 upconversion nanoprobes and to study their photothermal effects for the treatment of malignant melanoma. Methods: Morphological characteristics of the synthesized nanoprobes were examined by scanning electron microscopy. Their biocompatibility and biodistribution profiles were assessed through blood routine/biochemistry tests and the inductively coupled plasma/optical emission spectrometry-based analysis of tissue metal elements. Their photothermal conversion efficiency and their potential as contrast agents for upconversion luminescence (UCL)/magnetic resonance imaging (MRI) dual-modal imaging were tested. Efficacy in photothermal therapy, which was achieved by combining nanoprobes with near-infrared (NIR) irradiation, was evaluated in both A375 cell line and BALB/c mice models. The underlying mechanisms were interrogated by molecular approaches including the MTT assay, flow cytometry, semiquantitative PCR, western blot, and immunohistochemistry. Results: 1) Our synthesized NaYF4:Yb,Er@PE3@Fe3O4 nanoprobes exhibited a uniform cubic morphology with a diameter of ~50 nm. Subcutaneous administration led to no severe, long-lasting adverse effects in mice, possibly due to complete removal of these nanomaterials within one month. 2) Our nanoprobes possessed superior photothermal conversion efficiency and strong contrasting effects during UCL/MRI dual-modal imaging, corroborating their applications in imaging-guided photothermal therapy. 3) Combinatorial treatment of these nanoprobes with NIR irradiation induced profound apoptosis/necrosis in A375 cells. Similarly, the same treatment modality led to strong therapeutic effects in BALB/c mice implanted with A375 tumor xenografts. Mechanistic studies suggested an involvement of heat shock protein 70 in mediating the observed antitumor effects of our nanoprobes. Conclusion: Our study describes a convenient method to synthesize a new type of superparamagnetic upconversion nanoprobes, which possess high biocompatibility and can be used in imaging-guided photothermal therapy for the treatment of malignant melanoma. Importantly, our findings will promote clinical applications of NaYF4:Yb,Er@PE3@Fe3O4 as novel theranostic agents in treating melanoma and many other tumors.

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3.

Finding novel therapeutic agent for the treatment of cerebral ischemia is urgently required. These experiments explored the potential roles of 6-Gingerols (6G) in hypoxia-stimulated rat PC-12 cells. Cell viability, apoptosis and its related proteins were studied by the approaches of MTT assay, flow cytometry assay and Western blot analysis, respectively. In addition, whether 6G achieved its functions in hypoxia-induced injury through miR-103 was illustrated. Moreover, the associated signalling pathways were investigated. Obviously, hypoxia treatment blocked cell viability and enhanced apoptosis while this trend was ameliorated by 6G. Then we observed that hypoxia administration up-regulated miR-103 expression and 6G could further increase miR-103 expression in hypoxia-stimulated PC-12 cells. Inhibition of miR-103 attenuated the neuroprotective effects of 6G on hypoxia-treated PC-12 cells. Moreover, Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) was a target of miR-103 and BNIP3 upregulation also attenuated the neuroprotective impact of 6G on hypoxia-treated PC-12 cells. Hypoxia activated the p38MAPK and JNK pathways were inactivated by 6G. To sum up, 6G protected hypoxia-stimulated PC-12 cells through miR-103-mediatated down-regulation of BNIP3 by inhibiting p38 MAPK and JNK pathways. Highlights 6-Gingerols (6G) is a promising agent for cerebral ischemia therapy. The neuroprotective effects of 6G are mediated by miR-103 and BNIP3. Up-regulation of miR-103 exerts neuroprotective effects.

RETRACTED: Ginkgolides B alleviates hypoxia-induced PC-12 cell injury by up-regulation of PLK1.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief as panels within Figures 2D and 5D appear similar to each other. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request.

RETRACTED: Sappanone A prevents hypoxia-induced injury in PC-12 cells by down-regulation of miR-15a.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief. Given the comments regarding this article "The only experimental results presented in this paper are stylised, conventionalised 'western blots' that in fact resemble playful sardines, or tadpoles', the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editors-in-Chief decided to retract the article.

Baicalin alleviates 6-hydroxydopamine-induced neurotoxicity in PC12 cells by down-regulation of microRNA-192-5p.

Parkinson's disease (PD), which is caused by neurodegenerative disorder, has no effective treatment until now. Baicalin was reported to have neuroprotective effects. Hence, we investigated the effects of baicalin on PD in an in vitro cell model by using 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma PC12 cells. PC12 cells were stimulated by 6-OHDA and were treated with baicalin and/or transfected with miR-192-5p mimic or negative control (NC). Cell viability and apoptosis were examined by Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) analysis, respectively. The expression of p62, ratio of light chain (LC)3-II/LC3-I, miR-192-5p was detected by qRT-PCR. All protein expression levels were analyzed by western blot. We found that 6-OHDA significantly inhibited cell viability, induced apoptosis and autophagy, while baicalin reversed the results led by 6-OHDA. Moreover, baicalin negatively regulated expression of miR-192-5p. Under baicalin treatment, transfection with miR-192-5p mimic decreased cell viability and induced apoptosis and autophagy in 6-OHDA-treated cells compared with NC. In addition, the phosphorylation of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B (AKT) was statistically down-regulated by baicalin then thereafter reversed by miR-192-5p mimic. Baicalin reduced 6-OHDA-induced cell injury through down-regulation of miR-192-5p, as well as regulation of PI3K/AKT and MDM-2/p53 signal pathways.

Stem cell transplantation for treating stroke: status, trends and development.

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The majority of these articles were from the USA (854, 39.4%), with the journal Stroke publishing the most articles (145, 6.7%). Of the published articles, 143 were funded by the National Institutes of Health (accounting for 6.6% of total publications), and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided financial support ($130 million subsidy) for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA (ranked first place). China had the maximum number of registered research or clinical trials (10 projects).