Maintaining Drosha expression with Cdk5 inhibitors as a potential therapeutic strategy for early intervention after TBI

Huang Lu,Xia Li,Nie Tiejian,Cui Bozhou,Lu Jianjun,Lu Fangfang,Fan Feiyan,Ren Dongni,Lu Yuan,Gao Guodong,Yang Qian 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Traumatic brain injury (TBI) is a major cause of death and disability in adults. The pathological process of TBI involves a multifactorial cascade in which kinases have been proven contribute to interactions between relevant factors and amplification of signaling cascades. Cyclin-dependent kinase 5 (Cdk5) is a promising kinase that has been implicated in various brain disorders, including TBI. However, the mechanism by which Cdk5 induces neuronal damage remains unclear. Here, we show for the first time that Drosha, a key enzyme in microRNA biogenesis, is a pivotal substrate of abnormally activated Cdk5. Cdk5-mediated phosphorylation decreases Drosha expression and exacerbates nerve injury in TBI. We proved that maintaining Drosha expression via the administration of repurposed Cdk5 inhibitors that were previously studied in clinical trials is a promising approach for the early treatment of TBI. Together, our work identifies Drosha as a novel target for neuroprotective strategies after TBI and suggests Cdk5-mediated regulation of Drosha expression as a potential therapeutic strategy for early TBI intervention.

Phenotypic and genomic characteristics of Brevibacterium zhoupengii sp. nov., a novel halotolerant actinomycete isolated from bat feces

Huang Yuyuan,Dong Lingzhi,Gong Jian,Yang Jing,Lu Shan,Lai Xin-He,Jin Dong,Huang Qianni,Pu Ji,Liu Liyun,Xu Jianguo 한국미생물학회 2022 The journal of microbiology Vol.60 No.10

Two strictly aerobic, Gram-staining-positive, non-spore-forming, regular rod-shaped (approximately 0.7 × 1.9 mm) bacteria (HY170T and HY001) were isolated from bat feces collected from Chongzuo city, Guangxi province (22°20 54 N, 106°49 20 E, July 2011) and Chuxiong Yi Autonomous Prefecture, Yunnan province (25°09 10 N, 102°04 39 E, October 2013) of South China, respectively. Optimal growth is obtained at 25–28°C (range, 4–32°C) on BHI-5% sheep blood plate with pH 7.5 (range, 5.0–10.0) in the presence of 0.5– 1.0% NaCl (w/v) (range, 0–15% NaCl [w/v]). The phylogenetic and phylogenomic trees based respectively on the 16S rRNA gene and 845 core gene sequences revealed that the two strains formed a distinct lineage within the genus Brevibacterium, most closely related to B. aurantiacum NCDO 739T (16S rRNA similarity, both 98.5%; dDDH, 46.7–46.8%; ANI, 91.9–92.1%). Strain HY170T contained MK-8(H2), diphosphatidylglycerol (DPG) and phosphatidylglycerol (PG), galactose and ribose as the predominant menaquinone, major polar lipids, and main sugars in the cell wall teichoic acids, respectively. The meso-diaminopimelic acid (meso-DAP) was the diagnostic diamino acid of the peptidoglycan found in strain HY170T. Anteiso-C15:0 and anteiso-C17:0 were the major fatty acids (> 10%) of strains HY170T and HY001, with anteiso-C17:1A predominant in strain HY170T but absent in strain HY001. Mining the genomes revealed the presence of secondary metabolite biosynthesis gene clusters encoding for non-alpha poly-amino acids (NAPAA), ectoine, siderophore, and terpene. Based on results from the phylogenetic, chemotaxonomic and phenotypic analyses, the two strains could be classified as a novel species of the genus Brevibacterium, for which the name Brevibacterium zhoupengii sp. nov. is proposed (type strain HY170T = CGMCC 1.18600T = JCM 34230T).

MicroRNA-340-5p relieved chronic constriction injury-induced neuropathic pain by targeting Rap1A in rat model

Lu Gao,Xuehua Pu,Yujing Huang,Jing Huang 한국유전학회 2019 Genes & Genomics Vol.41 No.6

Objectives Neuropathic pain (NP) is one of the main challenges towards NP syndrome treatment. miR-340-5p exhibit different expression levels in NP models. Its effects on NP remained unclear. The objective of this study was to explore the potential regulation mechanisms of miR-340-5p in NP. Methods Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using mechanical withdrawal threshold (MWT). The inflammation response in CCI rats were determined by HE staining and ELISA assay. The target genes of miR-340-5p were verified by luciferase report assays. Results In CCI rats, level of miR-340-5p was down-regulated both in spinal cord tissues and isolated microglial cells. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in CCI rats, which were restored upon miR-340-5p overexpression. miR-340-5p overexpression also decreased inflammation as well as expression levels of COX- 2, IL-1β, TNF-α and IL-6 in CCI rats. Luciferase report assays revealed Rap1A was a target gene of miR-340-5p in the experimental model. Elevated miR-340-5p decreased Rap1A expression level in vitro and in vivo. Overexpression of Rap1A protein restored expression levels of COX-2, IL-1β, TNF-α and IL-6, reduced the PWT and PWL and increased inflammation response in CCI rats. Conclusion miR-340-5p alleviated CCI-induced NP by targeting Rap1A. miR-340-5p and Rap1A may be the potential treatment targets for NP therapeutics.

Influencing Factors and Contents of Audience Interaction Based Sports Live Broadcast

Lu Huang,Xuejiao Lin,Song, Jeho 한국스포츠학회 2020 한국스포츠학회지 Vol.18 No.4

본 연구는 스포츠 생방송 플랫폼에서 시청자의 상호작용에 영향을 미치는 요소와 내용을 탐구하였다. 문학 방법, 전문가 인터뷰 방법, 앙케이트 조사 방법, 수학 통계 방법, 스포츠 라이브 방송 플랫폼에서 시청자의 상호작용에 대한 영향 요소, 인터랙티브 내용, 구조적 차원을 규정하였다. 요인 분석을 사용하여 라이브 스포츠를 기반으로 청중 상호 작용 의 영향 요인과 내용을 선별하고 분석하였다. 연구를 통해 다음과 같은 결론을 얻었다. 첫째, '적극적 소통능력', '관중 간 고질성', '감정적 지원', '기능적 지원', '경기 관람 장애물' 등이 스포츠 관중의 주요 요소 간 상호작용에 영향을 미쳤다. 스포츠 생방송 플랫폼에서 시청자들 간의 상호작용에 대한 내용 차원은 '매력과 소통', '상호작용과 거부감', '도움행동', '관계발전' 등 4가지로 요약할 수 있다. 이번 연구를 통해 스포츠실황방송 플랫폼의 관리자들에게 이론적 참고자료를 제공 하고, 스포츠생방송 플랫폼의 목표 정비를 위한 근거를 제공하고자 한다. This work explores the influencing factors and content of audience interaction in sports live broadcast platforms. Through literature method, expert interview method, questionnaire survey method and mathematical statistics method, the influencing factors, interactive content and structural dimensions of the audience interaction in the sports live broadcast platform are defined. Use factor analysis to screen and analyze the influencing factors and content of audience interaction based on live sports. Through research, the following conclusions are obtained: First, "active communication ability", "heterogeneity among spectators", "emotional support", "functional support" and "perceived obstacles to watching games" affect the interaction between sports spectators’ major factor. The content dimensions of the interaction between viewers on the sports live broadcast platform can be summarized into four categories: "attraction and communication", "interference and repulsion", "help behavior", and "relationship development". Through this research, it can provide a theoretical reference for the managers of the sports live broadcast platform and provide a basis for the targeted maintenance of the sports live broadcast platform.

Highly Oriented Monolayer Graphene Grown on a Cu/Ni(111) Alloy Foil

Huang, Ming,Biswal, Mandakini,Park, Hyo Ju,Jin, Sunghwan,Qu, Deshun,Hong, Seokmo,Zhu, Zhili,Qiu, Lu,Luo, Da,Liu, Xiaochi,Yang, Zheng,Liu, Zhongliu,Huang, Yuan,Lim, Hyunseob,Yoo, Won Jong,Ding, Feng,Wa American Chemical Society 2018 ACS NANO Vol.12 No.6

<P>Fast-growth of single crystal monolayer graphene by CVD using methane and hydrogen has been achieved on “homemade” single crystal Cu/Ni(111) alloy foils over large area. Full coverage was achieved in 5 min or less for a particular range of composition (1.3 at.% to 8.6 at.% Ni), as compared to 60 min for a pure Cu(111) foil under identical growth conditions. These are the bulk atomic percentages of Ni, as a superstructure at the surface of these foils with stoichiometry Cu<SUB>6</SUB>Ni<SUB>1</SUB> (for 1.3 to 7.8 bulk at.% Ni in the Cu/Ni(111) foil) was discovered by low energy electron diffraction (LEED). Complete large area monolayer graphene films are either single crystal or close to single crystal, and include folded regions that are essentially parallel and that were likely wrinkles that “fell over” to bind to the surface; these folds are separated by large, wrinkle-free regions. The folds occur due to the buildup of interfacial compressive stress (and its release) during cooling of the foils from 1075 °C to room temperature. The fold heights measured by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) prove them to all be 3 layers thick, and scanning electron microscopy (SEM) imaging shows them to be around 10 to 300 nm wide and separated by roughly 20 μm. These folds are always essentially perpendicular to the steps in this Cu/Ni(111) substrate. Joining of well-aligned graphene islands (in growths that were terminated prior to full film coverage) was investigated with high magnification SEM and aberration-corrected high-resolution transmission electron microscopy (TEM) as well as AFM, STM, and optical microscopy. These methods show that many of the “join regions” have folds, and these arise from interfacial adhesion mechanics (they are due to the buildup of compressive stress during cool-down, but these folds are different than for the continuous graphene films-they occur due to “weak links” in terms of the interface mechanics). Such Cu/Ni(111) alloy foils are promising substrates for the large-scale synthesis of single-crystal graphene film.</P> [FIG OMISSION]</BR>

MC3T3-E1 osteoblast adhesion to laser induced hydroxyapatite coating on Ti alloy

Huang, Lu,Goddard, Samuel C.,Soundarapandian, Santhanakrishnan,Cao, Yu,Dahotre, Narendra B.,He, Wei Techno-Press 2014 Biomaterials and Biomechanics in Bioengineering Vol.1 No.2

An in vitro cell study evaluating cell adhesion to hydroxyapatite (HA) coated prosthetic Ti-6Al-4V alloy via laser treatment is presented in comparison with uncoated alloy. Based on our previous in vitro biocompatibility study, which demonstrated higher cell attachment and proliferation with MC3T3-E1 preosteoblast cells, the present investigation aims to reveal the effect of laser coating Ti alloy with HA on the adhesion strength of bone-forming cells against centrifugal forces. Remaining cells on different substrates after centrifugation were visualized using fluorescent staining. Semi-quantifications on the numbers of cells were conducted based on fluorescent images, which demonstrated higher numbers of cells retained on HA laser treated substrates post centrifugation. The results indicate potential increase in the normalized maximum force required to displace cells from HA coated surfaces versus uncoated control surface. The possible mechanisms that govern the enhancing effect were discussed, including surface roughness, chemistry, wettability, and protein adsorption. The improvement in cell adhesion through laser treatment with a biomimetic coating could be useful in reducing tissue damage at the prosthetic to bone junction and minimizing the loosening of prosthetics over time.

MC3T3-E1 osteoblast adhesion to laser induced hydroxyapatite coating on Ti alloy

Huang, Lu,Goddard, Samuel C.,Soundarapandian, Santhanakrishnan,Cao, Yu,Dahotre, Narendra B.,He, Wei Techno-Press 2014 Biomaterials and biomedical engineering Vol.1 No.2

An in vitro cell study evaluating cell adhesion to hydroxyapatite (HA) coated prosthetic Ti-6Al-4V alloy via laser treatment is presented in comparison with uncoated alloy. Based on our previous in vitro biocompatibility study, which demonstrated higher cell attachment and proliferation with MC3T3-E1 preosteoblast cells, the present investigation aims to reveal the effect of laser coating Ti alloy with HA on the adhesion strength of bone-forming cells against centrifugal forces. Remaining cells on different substrates after centrifugation were visualized using fluorescent staining. Semi-quantifications on the numbers of cells were conducted based on fluorescent images, which demonstrated higher numbers of cells retained on HA laser treated substrates post centrifugation. The results indicate potential increase in the normalized maximum force required to displace cells from HA coated surfaces versus uncoated control surface. The possible mechanisms that govern the enhancing effect were discussed, including surface roughness, chemistry, wettability, and protein adsorption. The improvement in cell adhesion through laser treatment with a biomimetic coating could be useful in reducing tissue damage at the prosthetic to bone junction and minimizing the loosening of prosthetics over time.

Cell-Penetrating Peptide-Modified PLGA Nanoparticles for Enhanced Nose-to-Brain Macromolecular Delivery

Lu Yan,Huiyuan Wang,Yifan Jiang,Jinhua Liu,Zhao Wang,Yongxin Yang,Shengwu Huang,Yongzhuo Huang 한국고분자학회 2013 Macromolecular Research Vol.21 No.4

Macromolecular drugs become an essential part in neuroprotective treatment. However, the nature of ineffective delivery crossing the blood brain barrier (BBB) renders those macromolecules undruggable for clinical practice. Recently, brain target via intranasal delivery have provided a promising solution to circumventing the BBB. Despite the direct route from nose to brain (i.e. olfactory pathway), there still are big challenges for large compounds like proteins to overcome the multiple delivery barriers such as nasal mucosa penetration, intracellular transport along the olfactory neuron, and diffusion across the heterogeneous brain compartments. Herein presented is an intranasal strategy mediated by cell-penetrating peptide modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the delivery of insulin to the brain, a potent therapeutic against Alzheimer’s disease. The results revealed that the cell-penetrating peptide can potentially deliver insulin into brain via the nasal route, showing a total brain delivery efficiency of 6%. It could serve as a potential treatment for neurodegenerative diseases.

Ginseng-plus-Bai-Hu-Tang ameliorates diet-induced obesity, hepatic steatosis, and insulin resistance in mice

Lu, Hsu-Feng,Lai, Yu-Heng,Huang, Hsiu-Chen,Lee, I-Jung,Lin, Lie-Chwen,Liu, Hui-Kang,Tien, Hsiao-Hsuan,Huang, Cheng The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. Methods: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. Results: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. Conclusion: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.

Mining Highly Reliable Dense Subgraphs from Uncertain Graphs

( Lu Yihong ),( Huang Ruizhi ),( Huang Decai ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.6

The uncertainties of the uncertain graph make the traditional definition and algorithms on mining dense graph for certain graph not applicable. The subgraph obtained by maximizing expected density from an uncertain graph always has many low edge-probability data, which makes it low reliable and low expected edge density. Based on the concept of β-subgraph, to overcome the low reliability of the densest subgraph, the concept of optimal β-subgraph is proposed. An efficient greedy algorithm is also developed to find the optimal β-subgraph. Simulation experiments of multiple sets of datasets show that the average edge-possibility of optimal β-subgraph is improved by nearly 40%, and the expected edge density reaches 0.9 on average. The parameter β is scalable and applicable to multiple scenarios.