Invasive fungal infections are associated with high mortality rates. The proliferation of C. albicans is mainly limited by the innate immune system, in which phagocytic cells, especially polymorphonuclear leukocytes (PMNs), play an important role. Several studies have shown that antihypertensive drugs can cause an increased risk of infection, but whether antihypertensive drugs affect the killing activity of PMNs against C. albicans has not been studied. Here, we demonstrated that nifedipine (NIF) inhibits neutrophil killing of C. albicans. NIF reduces the production of reactive oxygen species (ROS) and pro-inflammatory cytokines in PMNs by inhibiting the phosphorylation of NF-κB, thereby inhibiting killing of PMNs against C. albicans. Next, using the C. albicans injection mouse model of fungal sepsis, we observed NIF can exacerbate infection in mice. Finally, our study identified patients with fungal infections from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and analysis of the data showed that NIF led to increased length of stay. In summary, we have found that the antihypertensive drug NIF can negatively regulate antifungal immunity by inhibiting the phosphorylation of the PMNs transcription factor NF-κB.IMPORTANCEIn this study, we demonstrated that NIF inhibited the ability of neutrophils to kill C. albicans by suppressing NF-κB phosphorylation, thereby reducing the production of ROS and pro-inflammatory cytokines in neutrophils. Furthermore, analysis of the MIMIC database revealed that NIF prolonged hospitalization duration in patients with fungal infections. Collectively, our findings suggest that antihypertensive drugs may exert adverse effects on the treatment of fungal infections, which could provide new insights for optimizing therapeutic strategies in clinical practice.

Post-stroke cognitive impairment (PSCI) is a common complication of strokes and is associated with the demyelination of nerve fibers. AMX0035, a drug currently used to treat motor neuron diseases, may aid in preventing oligodendrocyte apoptosis and alleviating demyelination by targeting the pathways involved in ERS and mitochondrial dysfunction. All animals were randomly divided into four groups: the sham, sham+AMX0035, middle cerebral artery occlusion (MCAO), and MCAO+AMX0035 group. The Morris water maze was used to test cognitive function, and changes in myelin structure in the brain were investigated using transmission electron microscopy (TEM), Luxol fast blue (LFB) staining, and myelin basic protein (MBP) immunofluorescence staining. Western blot was performed to detect proteins associated with ER stress and mitochondrial dysfunction, and double-labeling immunofluorescence was utilized to localize oligodendrocytes and apoptosis-related proteins. Neurological function scores and TTC staining confirmed the successful establishment of the MCAO rat model. The Morris water maze experiment revealed impaired cognitive function in MCAO rats, which significantly improved following the AMX0035 intervention. TEM and LFB staining showed the disrupted myelin structure in the MCAO group, while AMX0035 effectively ameliorated this myelin damage. Immunofluorescence examination and Western blot revealed the decreased expression of MBP in MCAO rats, increasing with AMX0035 treatment. TUNEL staining demonstrated increased cell apoptosis in MCAO rats, which was reduced following AMX0035 therapy. Western blot detected significant increases in proteins associated with the ER stress pathway and proteins linked to mitochondrial dysfunction in the MCAO group, all of which were downregulated after AMX0035 intervention. Double-labeling immunofluorescence staining revealed a significant increase in the number of cytochrome c+ and caspase 12+ oligodendrocyte cells in MCAO rats, which decreased after AMX0035 administration. The activation of ER stress and mitochondrial dysfunction pathways following MCAO led to oligodendrocyte damage and apoptosis. AMX0035 can inhibit these pathways, reduce oligodendrocyte apoptosis, and alleviate demyelination, thereby improving PSCI.

Subarachnoid hemorrhage refers to an uncommon but severe subtype of stroke leading to high mortality and disability rates. Electroacupuncture, a traditional Chinese medical therapy combined with modern technology, shows evident curative effects on cerebral vascular diseases. This study attempts to investigate the possible treatment effects and mechanisms of EA on early brain injury after SAH. Data were gathered among sham group, SAH-induced group, and EA-treated group of male SD rats, concerning mortality rates, weight loss, rotarod latencies, cerebral blood flow, cell apoptosis, pro-inflammatory cytokines releasing, apoptotic protein level, microglia activation and related signal pathway. All results were collected 24-72 h after SAH induction. EA treatment demonstrated significant improvement on motor function 24 h after SAH without significant changes in mortality rate, weight loss, and cerebral blood flow. Another important finding was that EA regulated Bax and Bcl-2 imbalance and reduced cleaved casepase-3 caused by SAH. Additionally, levels of TNF-α, IL-1β, IL-6 were suppressed. The neuron apoptosis was suppressed by EA. The M1 polarization of activated microglia decreased while M2 polarized phenotype increased after EA treatment. Furthermore, pSTAT3-NOX2 signal axis, the M1 phenotype related activation pathway, was depressed after EA treatment. These findings suggested that EA improved motor deficits and ameliorated early brain injury after SAH probably via decreasing neuron apoptosis and anti-inflammation, which may involve modulation of microglia polarization. Taken together, EA may be a potential therapy for SAH treatment.

目的:研究幼年胆红素脑病(BE)模型大鼠海马中水通道蛋白4(AQP4)的表达变化,并且探究其与海马细胞凋亡及认知功能障碍的关系.方法:采用7 d龄SD幼年大鼠经小脑延髓池注射未结合胆红素(UCB)建立BE模型,根据UCB作用时间的不同将其分为12 h、24 h、48 h、72 h和7 d组.采用HE和Nissl染色观察各组海马病理变化;应用TUNEL染色法检测海马细胞凋亡;应用Western Blot检测海马AQP4、LAMP1、caspase-3和胶质纤维酸性蛋白(GFAP)的表达变化;应用免疫荧光染色检测海马AQP4、LAMP1和GFAP的表达变化及AQP4+/GFAP+细胞数量的变化.结果:HE及Nissl染色显示,随着UCB作用时间的延长,海马神经细胞间隙不断变大,空泡逐渐增多,Nissl小体数量减少.TUNEL染色法显示海马凋亡细胞数量在UCB作用24 h组最多(P＜0.05).Western Blot结果显示,随着UCB作用时间的延长,海马细胞中caspase-3和LAMP1均上升至24 h达峰值(P＜0.05).免疫荧光结果显示,AQP4和GFAP均增加至48 h表达最高(P＜0.05),AQP4+/GFAP+细胞数量在48 h组达最多(P＜0.05).结论:UCB的神经毒性作用可导致海马细胞凋亡增加至24 h达峰值,继发星型胶质细胞代偿性增生,并伴随AQP4的表达增加至48 h达峰值,以上变化可能与BE的认知功能障碍具有密切联系.

笔者在解剖1具男尸过程中,发现其两侧椎动脉起始处走行均异常,且与交感神经节关系密切.现为积累解剖学资料,报道如下. 10％甲醛固定的男尸1具,年龄约60岁,身高约162 cm,解剖出颈部各层次,充分暴露及修洁颈部的血管、神经,观察拍照,并测量血管外径及长度.本例标本左、右两侧椎动脉均起自锁骨下动脉,呈"S"形上行.

Subarachnoid hemorrhage (SAH) is a devastating cerebral vascular disease which causes neurological deficits including long-term cognitive deficit. Demyelination of white matter is correlated with cognitive deficit in SAH. Electroacupuncture (EA) is a traditional Chinese medical treatment which protects against cognitive deficit in varies of neurological diseases. However, whether EA exerts protective effect on cognitive function in SAH has not been investigated. The underlying mechanism of remyelination regulated by EA remains unclear. This study aimed to investigate the protective effects of EA on cognitive deficit in a rat model of SAH. SAH was induced in SD rats (n = 72) by endovascular perforation. Rats in EA group received EA treatment (10 min per day) under isoflurane anesthesia after SAH. Rats in SAH and sham groups received the same isoflurane anesthesia with no treatment. The mortality rate, neurological score, cognitive function, cerebral blood flow (CBF), and remyelination in sham, SAH and EA groups were assessed at 21 d after SAH.EA treatment alleviated cognitive deficits and myelin injury of rats compared with that in SAH group. Moreover, EA treatment enhanced remyelination in white matter and promoted the differentiation of OPCs after SAH. EA treatment inhibited the expression of Id2 and promoted the expression of SOX10 in oligodendrocyte cells. Additionally, the cerebral blood flow (CBF) of rats was increased by EA compared with that in SAH group. EA treatment exerts protective effect against cognitive deficit in the late phase of SAH. The underlying mechanisms involve promoting oligodendrocyte progenitor cell (OPC) differentiation and remyelination in white matter via regulating the expression of Id2 and SOX10. The improvement of CBF may also account for the protective effect of EA on cognitive function. EA treatment is a potential therapy for the treatment of cognitive deficit after SAH.

Objective To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism. Design Animal experiment study. Setting Institute of Neuroscience of Chongqing Medical University. Interventions Total of 69 Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline. Outcome measures: The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively. Results In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C. Conclusions Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

BACKGROUND:Specific highly polarized aquaporin-4 (AQP4) expression is reported to play a crucial role in blood-brain barrier (BBB) integrity and brain water transport balance. The upregulation of polymerase δ-interacting protein 2 (Poldip2) was involved in aggravating BBB disruption following ischemic stroke. This study aimed to investigate whether Poldip2-mediated BBB disruption and cerebral edema formation in mouse bacterial meningitis (BM) model occur via induction of AQP4 polarity loss. METHODS AND RESULTS:Mouse BM model was induced by injecting mice with group B hemolytic streptococci via posterior cistern. Recombinant human Poldip2 (rh-Poldip2) was administered intranasally at 1 hour after BM induction. Small interfering ribonucleic acid (siRNA) targeting Poldip2 was administered by intracerebroventricular (i.c.v) injection at 48 hours before BM induction. A specific inhibitor of matrix metalloproteinases (MMPs), UK383367, was administered intravenously at 0.5 hour before BM induction. Western blotting, immunofluorescence staining, quantitative real-time PCR, neurobehavioral test, brain water content test, Evans blue (EB) permeability assay, transmission electron microscopy (TEM), and gelatin zymography were carried out. The results showed that Poldip2 was upregulated and AQP4 polarity was lost in mouse BM model. Both Poldip2 siRNA and UK383367 improved neurobehavioral outcomes, alleviated brain edema, preserved the integrity of BBB, and relieved the loss of AQP4 polarity in BM model. Rh-Poldip2 upregulated the expression of MMPs and glial fibrillary acidic protein (GFAP) and downregulated the expression of β-dystroglycan (β-DG), zonula occludens-1 (ZO-1), occludin, and claudin-5; whereas Poldip2 siRNA downregulated the expression of MMPs and GFAP, and upregulated β-DG, ZO-1, occludin, and claudin-5. Similarly, UK383367 downregulated the expression of GFAP and upregulated the expression of β-DG, ZO-1, occludin, and claudin-5. CONCLUSION:Poldip2 inhibition alleviated brain edema and preserved the integrity of BBB partially by relieving the loss of AQP4 polarity via MMPs/β-DG pathway.

目的 利用原代星形胶质细胞慢性缺氧模型,探讨在缺氧状态下星形胶质细胞水通道蛋白9(aquaporin-9,AQP9)的表达变化及其调控机制.方法 将Sprague-Dawley(SD)大鼠原代星形胶质细胞随机分为对照组和缺氧损伤模型组,其中缺氧损伤模型分别缺氧12h、24h、48h、72h,共计4个时间点;采用乳酸(lactic acid,LD)和乳酸脱氢酶活性(lactate dehydrogenase,LDH)试剂盒分别测定培养液中LD含量及LDH活性;运用免疫荧光法检测各组AQP9的分布及表达水平,运用免疫印迹法测定各组AQP9,HIF-1α和p38-MAPK的相对表达量.结果 与对照组相比,缺氧损伤模型组细胞培养液中LD含量和LDH活性均増高,且随缺氧时间延长逐渐上升,于72h达高峰;免疫荧光结果显示,对照组中,AQP9在细胞胞膜和胞浆的表达呈弱阳性,而在缺氧组中,随着缺氧时间的延长,AQP9的表达逐渐增强;免疫印迹结果显示,与对照组相比,AQP9、HIF-1α、p-p38/p38表达逐渐増加,而给予p38抑制剂(SB203580)可以降低AQP9的表达.结论 星形胶质细胞慢性缺氧后,细胞胞外的乳酸浓度增加,AQP9的表达上调,表达上调可能与乳酸的转运有关;p38-MAPK信号通路可能协同调控AQP9的表达.

目的 探讨水通道蛋白3(AQP3)的表达变化与人不同病理级别星形细胞瘤的关系.方法 收集人各个级别星形细胞瘤标本50例,取肿瘤周围相对正常脑组织作为对照组,采用石蜡切片免疫组织化学、Western blot及反转录聚合酶链式反应(RT-PCR)等技术观察AQP3及其mRNA的表达变化.结果 50例标本中Ⅰ级5例,Ⅱ级11例,Ⅲ级20例,Ⅳ级14例,免疫组织化学显示AQP3主要分布在星形细胞瘤组织细胞内,呈不均匀分布;Western blot和RT-PCR结果显示在对照组及各肿瘤组织中均可观察到AQP3及其mR-NA特定的免疫阳性反应产物,且高级别肿瘤组织显示灰度比低级别和对照组明显增强.免疫组织化学半定量分析与Western blot、RT-PCR结果一致显示,与对照组比较,高级别星形细胞瘤组织AQP3及其mRNA表达上调(P<0.05),而低级别星形细胞瘤组织中无明显变化(P>0.05).结论 AQP3及其mRNA仅在人高级别星形细胞瘤组织中表达增强,AQP3的表达变化与人星形细胞瘤的恶性程度有关.

为了加强基础与临床知识的联系和渗透,以及培养学生的临床胜任力,重庆医科大学进行了器官系统教学模式的改革.此外,学校开展了本科生创新实验课题计划,以培养学生的创新能力和科研思维能力.医学生在参与创新实验课题的过程中,通过查阅文献资料以确定选题、撰写申请书、开展实验及写作论文等不同环节的学习和锻炼,有利于扩大其知识面,增强其自主学习能力、动手能力和团队合作精神等,从而促进其对器官系统课程知识的学习.因此,鼓励学生参加创新实验课题并做好各环节的工作,对于提高器官系统课程的学习效果,培养高素质的创新型医学人才具有重要意义.

It is an important way to improve the teaching quality by carrying out innovative experiments among medical students. In the process of experimental teaching, anatomy teachers expand the anatomy knowledge to basic scientific research techniques, so as to enhance students' confidence in participating in innovative experimental projects. Meanwhile, the teachers combine introduction of the anatomical structures with hot medical research issues, in order to help students to select appropriate innovative experimental topics. What's more, the new media teaching is integrated into the teaching of anatomy, enlightening students to perfect the experimental designs. Finally, in the teaching practice of regional anatomy, students are guided to carry out innovative experiments and write research papers. Abovementioned measures not only improve the teaching quality of anatomy, but also improve the students' scientific research ability, laying a foundation for them to participate in innovative experimental projects.

Progranulin (PGRN) is an autocrine growth factor with numerous physiological and pathologic roles. Previous reports demonstrated PGRN could increase dermal fibroblasts in wound healing and activate cancer-associated fibroblasts in some cancers. Because systemic sclerosis (SSc) is a prototypical fibrosis-related disorder, here, the aim was to clarify the role and mechanism of PGRN in bleomycin (BLM)-induced model of SSc for the first time. It was observed that the serum PGRN levels were increased in SSc patients compared with healthy controls. Immunohistology and quantitative RT-PCR demonstrated that PGRN was also elevated in the lesion from the mice model of BLM-induced dermal fibrosis. In addition, in BLM-treated mice, PGRN deficiency not only attenuated dermal fibrosis but also decreased the differentiation of myofibroblasts. The reduced progression of skin sclerosis in PGRN-deficient mice was associated with down-regulation of transforming growth factor (TGF)-β receptor I (TβR I) and decreased level of phosphorylated Smad3, with correspondingly impaired expression of its downstream target gene connective tissue growth factor (CTGF) in skin lesion. In contrast, exogenous PGRN significantly increased the level of TβR I and phosphorylated Smad3 in cultured mouse fibroblasts. This study demonstrates that PGRN plays a promoting role in the development of dermal fibrosis through the activation of the TGF-β/Smad3 signaling via up-regulation of TβR I. PGRN may be a new therapeutic target in SSc.

Purpose Investigating the roles of phosphorylated epidermal growth factor receptor (pEGFR) in the recovery of neural function after decompression of CSCI, therefore provide experimental basis for the development of therapeutic strategies and medicines for treating CSCI. Methods A CSCI model was established with a customized device, and was then subjected to spinal decompression. The motor functions were monitored by the Basso, Beattie & Bresnahan（BBB） locomotor rating scale; the number of axonal myelinated fibers was estimated by staining with luxol fast blue (LFB); pEGFR and phosphorylated Akt1 (pAkt1) were detected by Western blot; pEGFR+-NG2+(NG2+ cells are precursor to oligodendrocytes and pAkt1+-NG2+ cells were detected by double-labeling immunefluorescence assay. Results After decompression of CSCI, the BBB scores and the number of myelinated nerve fibers gradually increased with time. Meanwhile, the expression of pEGFR and pAkt1 were up-regulated and the number of pEGFR+-NG2+ and pAkt1+-NG2+ cells increased consistent with the changes of motor functions and the number of myelinated nerve fibers. Whereas, significant decreases in BBB scores, expression level of pAkt1, as well as numbers of myelinated nerve fibers, and pAkt1+-NG2+ cells were observed after inhibition of expression. Conclusions Up-regulated expression of pEGFR can promote recovery of neurological functions in rats with CSCI. This effect is achieved by activation of pAkt1（a downstream signal molecule of pEGFR）, which subsequently promotes the proliferation of oligodendrocyte precursor cells (OPCs).

神经细胞水肿是胆红素脑病(bilirubin encephalopathy,BE)发生发展过程中的重要病理变化.水通道蛋白-4(aquaporin-4,AQP4)的表达及分布异常与多种疾病所致细胞毒性脑水肿的发生发展具有密切联系.但胆红素脑病中AQP4的表达变化规律及其在病理进展中的作用尚不清楚.采用7日龄SD大鼠小脑延髓池注射胆红素溶液的方法,建立新生大鼠胆红素脑病模型.胆红素脑病模型根据胆红素作用时间的不同,分为12h、24 h、48 h、72 h和7d组.采用HE及尼氏染色,检测各新生大鼠脑组织的病理改变;应用透射电镜(TEM),检测胆红素作用24 h后,鼠脑组织超微结构的变化;应用免疫荧光及Western印迹,检测AQP4在脑组织中的表达变化.通过上述实验,以探讨AQP4的表达变化与胆红素所致脑损伤的关系.HE及尼氏染色结果显示,随着胆红素沉积时间的延长,神经细胞逐渐肿胀,细胞间隙增大,尼氏小体数量逐渐减少;电镜结果显示,胆红素脑病24 h后神经细胞线粒体出现肿胀;免疫荧光染色显示,24 h组AQP4的表达范围明显增加,其后表达范围逐渐减少,表达强度也随之减弱;Western印迹结果显示,AQP4表达在不同时间点呈现先增高后降低的趋势,在24 h达到峰值(24 h组1.38±0.11 vs对照组0.87±0.21,P＜0.05),在之后的各时间点上,AQP4的表达呈现下降趋势,而72 h组与7d组AQP4表达均低于48 h组(P＜0.05),基本恢复到对照组的表达水平(P＞0.05).上述结果提示,胆红素脑病中胆红素的毒性作用将引起AQP4表达量的改变,AQP4的表达变化与胆红素脑病中细胞毒性脑水肿的发生相关,并且可能在胆红素脑病脑损伤的进展中发挥作用.

Engineered conduction tissues (ECTs) are cardiac conduction tissues fabricated in vitro to allow for more precisely targeted in vivo transplantation therapy. The transplantation of ECTs may be ideal for the treatment of atrioventricular conduction block and could have a significant impact on the future application of biological pacemakers. However, there is little published information regarding the conduction function of ECTs in vivo. In the present study, ECTs were constructed by seeding cardiac progenitor cells (CPCs) into a collagen sponge and were then transplanted into animal hearts to determine whether they could act as an atrioventricular conduction pathway. The results demonstrated that the transplanted ECTs were adequately vascularized at the early stage of transplantation and could survive in the atrioventricular junction area of rats. A large number of myocardial tissue (≥29% of the new muscle fiber tissue formation area in the implanted ECTs) were observed by Masson's trichrome staining at 60 days post-transplantation. Positive staining for connexin-40, connexin-43, HCN2 and cTnT was exhibited during the period of 20 to 90 days post-transplantation. This result suggested that the transplanted ECTs formed gap junctions with the allogeneic myocardium and developed into cardiac conduction tissues with certain myocardial components. Electrocardiography (ECG) confirmed that there was a clear pre-excitation syndrome in the rats transplanted with ECTs during the period of 20 to 90 days post-transplantation. The recovery rate in the rats implanted with ECTs was 61.54% within 1 h following atrioventricular block, and the heart rhythm following recovery was close to normal. By contrast, the recovery rate was only 4.17% in the rats implanted with blank collagen sponges (BCSs), and none of the sham rats exhibited atrioventricular block recovery. In conclusion, ECTs can survive and mechanically integrate with the allogeneic myocardium following transplantation into rat hearts. An atrioventricular accessory pathway similar to Kent bundles could be established between the atria and ventricles of rats following implantation. It is suggested that ECTs may be a potential substitution therapy for atrioventricular conduction block.

This study aimed to assess the role of microRNAs (miRNAs) in regulating monocarboxylate transporter-1 (MCT1) expression in rat brain after permanent focal cerebral ischemia to identify a new target for early treatment of cerebral ischemia. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion (pMCAO) in rats. Morphology and protein expression levels of MCT1 were assessed by immunofluorescence and Western blotting. Using bioinformatics and double luciferase reporter assays, rno-miR-124-3p was selected as a direct target for rat MCT1. Expression of rno-miR-124-3p after pMCAO was detected. Then, rats were treated with rno-miR-124-3p agomir via lateral ventricle injection, and after 6 h or 24 h ischemia, rno-miR-124-3p expression and gene and protein expression of MCT-1 were detected by qRT-PCR and Western blotting. Brain infarction was identified by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Results showed that pMCAO induced brain infarction and increased the expression of MCT1. The levels of rno-miR-124-3p after pMCAO were in contrast to those of MCT1 protein in ischemic region, while declined after 3, 6 and 12 h of pMCAO in ischemic penumbra. After administration of rno-miR-124-3p agomir, MCT1 mRNA and protein levels were increased after 6 h of pMCAO, while decreased after 24 h of pMCAO. Meanwhile, rno-miR-124-3p levels increased after both times. TTC staining showed treatment with rno-miR-124-3p agomir reduced brain infarction. The role of rno-miR-124-3p in regulating MCT1 was as a positive regulator after 6 h of pMCAO, while a negative regulator after 24 h of pMCAO, however, both activities had protective effects against cerebral ischemia.

IntentionLong noncoding RNAs, transcribed from a recently discovered class of noncoding genes, may play a critical role in regulating cellular processes, such as cell proliferation and apoptosis, as well as in cancer progression and metastasis. We previously detected the induction of growth arrest–specific 5 (GAS5) during glioma cell death. However, the function and underlying mechanism of GAS5 in human gliomas remain to be elucidated.MethodsCell proliferation was detected using CellTiter 96® AQueous Non‐Radioactive Cell Proliferation Assay (MTS) and tumorigenicity assay in nude mice. Wound‐healing assay and transwell assay were utilized to examine the effects of GAS5 expression on glioma cells migration and invasion. In situ hybridization (ISH) was performed to evaluate GAS5 and microRNA (miR)‐18a‐5p levels in tissue microarrays. The relationship between GAS5 and miR‐18a‐5p was evaluated by quantitative reverse‐transcription polymerase chain reaction and RNA precipitation.ResultsIn this study, we demonstrated that overexpression of GAS5 inhibits malignant phenotypes in glioma cells, including proliferation, migration, and invasion, whereas GAS5 knockdown enhances these phenotypes. We further observed Argonaute 2–dependent reciprocal repression between GAS5 and miR‐18a‐5p in glioma cells. Downregulation of GAS5 and upregulation of miR‐18a‐5p were observed in glioma tissue microarrays relative to normal brain tissue by ISH. By deletion analysis, we identified one miR‐18a‐5p‐binding site within exon 2 of GAS5 that is partially responsible for the tumor‐suppressor functions of GAS5.ConclusionTaken together, our findings suggest that GAS5 is a tumor suppressor in human gliomas that acts in part by repressing miR‐18a‐5p.

Senescence has become a hot point issue in recent decades and requires urgent attention. As a novel and effective antioxidant, hydrogen has been proved to alleviate cellular senescence in endothelial cells in vitro. However, the effects and mechanisms of hydrogen on senescence in vivo are still unclear. In the present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow-derived stem cells (BMSCs) were harvested for the detection of hydrogen antisenescence effects and mechanisms. The results showed that the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive cells was reduced in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a better proliferation ability, showed more effectively tri-lineage differentiation potential, and had less percentage of cells in G1 cell cycle arrest than the control cells. Additionally, HRS administration inhibited the production of intracellular reactive oxygen species (ROS) and decreased the expression of senescence-related proteins p53 and p21. Our results revealed that hydrogen could alleviate cellular senescence in vivo. And the underlying mechanism of antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling pathway. Thus, hydrogen could be a new and convenient strategy for alleviating senescence and for therapy of age-related diseases.

ABSTRACT Curcumin is a natural product with several anti‐Alzheimer's disease (AD) neuroprotective properties. This study aimed to investigate the effects of curcumin on memory deficits, lactate content, and monocarboxylate transporter 2 (MCT2) in APP/PS1 mouse model of AD. APP/PS1 transgenic mice and wild‐type (WT) C57BL/6J mice were used in the present study. Spatial learning and memory of the mice was detected using Morris water‐maze test. Cerebral cortex and hippocampus lactate contents were detected using lactate assay. MCT2 expression in the cerebral cortex and hippocampus was examined by immunohistochemistry and Western blotting. Results showed that spatial learning and memory deficits were improved in curcumin‐treated APP/PS1 mouse group compared with those in APP/PS1 mice group. Brain lactate content and MCT2 protein level were increased in curcumin‐treated APP/PS1 mice than in APP/PS1 mice. In summary, our findings indicate that curcumin could ameliorate memory impairments in APP/PS1 mouse model of AD. This phenomenon may be at least partially due to its improving effect on the lactate content and MCT2 protein expression in the brain. Anat Rec, 302:332–338, 2019. © 2018 Wiley Periodicals, Inc.