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Article ; Online: Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine

Xiaoyue Hu / Miao Jing / Yanping Wang / Yanshan Liu / Ying Hua

Frontiers in Molecular Neuroscience, Vol

2023 Volume 16

Abstract: ObjectiveWe admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in ... ...

Abstract	ObjectiveWe admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response.MethodsWe described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant.ResultsWES identified a novel de novo SCN2A variant (c.468 G > C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that SCN2A-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na+ channel, all of which suggested a loss-of-function (LOF) of Nav1.2 channel.ConclusionWe showed the importance of functional analysis for a SCN2A variant with unknown significance to determine pathogenicity, drug reactions, and genotype–phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some SCN2A-related epilepsies requires vigilance to assess the possibility of epilepsy worsening.
Keywords	early-onset epileptic encephalopathy ; SCN2A ; oxcarbazepine ; patch-clamp ; precise medicine ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
Subject code	616
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A lysosomes and mitochondria dual-targeting AIE-active NIR photosensitizer

Shaozhen Wang / Yunhui Liao / Zhaoji Wu / Yihong Peng / Yuchen Liu / Yinghua Chen / Longquan Shao / Zhijie Zeng / Yanshan Liu

Materials Today Bio, Vol 21, Iss , Pp 100721- (2023)

Constructing amphiphilic structure for enhanced antitumor activity and two-photon imaging

2023

Abstract: Development of lysosomes and mitochondria dual-targeting photosensitizer with the virtues of near-infrared (NIR) emission, highly efficient reactive oxygen generation, good phototoxicity and biocompatibility is highly desirable in the field of imaging- ... ...

Abstract	Development of lysosomes and mitochondria dual-targeting photosensitizer with the virtues of near-infrared (NIR) emission, highly efficient reactive oxygen generation, good phototoxicity and biocompatibility is highly desirable in the field of imaging-guided photodynamic therapy (PDT) for cancer. Herein, a new positively charged amphiphilic organic compound (2-(2-(5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)vinyl)-3-methylbenzo[d]thiazol-3-ium iodide) (ADB) based on a D-A-π-A structure is designed and comprehensively investigated. ADB demonstrates special lysosomes and mitochondria dual-organelles targeting, bright NIR aggregation-induced emission (AIE) at 736 nm, high singlet oxygen (1O2) quantum yield (0.442), as well as good biocompatibility and photostability. In addition, ADB can act as a two-photon imaging agent for the elaborate observation of living cells and blood vessel networks of tissues. Upon light irradiation, obvious decrease of mitochondrial membrane potential (MMP), abnormal mitochondria morphology, as well as phagocytotic vesicles and lysosomal disruption in cells are observed, which further induce cell apoptosis and resulting in enhanced antitumor activity for cancer treatment. In vivo experiments reveal that ADB can inhibit tumor growth efficiently upon light exposure. These findings demonstrate that this dual-organelles targeted ADB has great potential for clinical imaging-guided photodynamic therapy, and this work provides a new avenue for the development of multi-organelles targeted photosensitizers for highly efficient cancer treatment.
Keywords	Photosensitizer ; Aggregation-induced emission ; Dual-organelles targeting ; Near-infrared ; Photodynamic therapy ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bioactive effects of nonthermal argon-oxygen plasma on inorganic bovine bone surface

Chengzan Wu / Kai Ma / Hongmei Zhao / Qian Zhang / Yanshan Liu / Na Bai

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract As a commonly used bone substitute material in the clinic, inorganic bovine bone has the characteristics of osteoconduction but not osteoinduction. This study aimed to treat inorganic bovine bone using nonthermal argon-oxygen plasma (NTAOP) to ... ...

Abstract	Abstract As a commonly used bone substitute material in the clinic, inorganic bovine bone has the characteristics of osteoconduction but not osteoinduction. This study aimed to treat inorganic bovine bone using nonthermal argon-oxygen plasma (NTAOP) to obtain greater bioreactivity for enhancing adhesion, proliferation and differentiation of mouse preosteoblast MC3T3-E1 cells. In this study, inorganic bovine bone was activated by NTAOP, and the surface characteristics were analyzed. MC3T3-E1 cells were then seeded onto the surface of inorganic bovine bone. Cell morphology, proliferation and osteogenic differentiation were examined. There was no obvious change in the surface morphology of specimens between the two groups. Regarding the elemental composition of the material, the amount of surface carbon was reduced, whereas oxygen, phosphorus and calcium levels were increased in the NTAOP group. Further studies showed that the NTAOP groups performed better than their untreated counterparts in terms of supporting cell proliferation and differentiation. Inorganic bovine bone treated with NTAOP can promote preosteoblast adhesion, proliferation and differentiation.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bioactive Effects of Low-Temperature Argon–Oxygen Plasma on a Titanium Implant Surface

Lei Wang / Weiwei Wang / Hongmei Zhao / Yanshan Liu / Jie Liu / Na Bai

ACS Omega, Vol 5, Iss 8, Pp 3996-

2020 Volume 4003

Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	American Chemical Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bi-potential hPSC-derived Müllerian duct-like cells for full-thickness and functional endometrium regeneration

Lin Gong / Nanfang Nie / Xilin Shen / Jingwei Zhang / Yu Li / Yixiao Liu / Jiaqi Xu / Wei Jiang / Yanshan Liu / Hua Liu / Bingbing Wu / XiaoHui Zou

npj Regenerative Medicine, Vol 7, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Stem cell-based tissue regeneration strategies are promising treatments for severe endometrial injuries. However, there are few appropriate seed cells for regenerating a full-thickness endometrium, which mainly consists of epithelia and stroma. ... ...

Abstract	Abstract Stem cell-based tissue regeneration strategies are promising treatments for severe endometrial injuries. However, there are few appropriate seed cells for regenerating a full-thickness endometrium, which mainly consists of epithelia and stroma. Müllerian ducts in female embryonic development develop into endometrial epithelia and stroma. Hence, we first generated human pluripotent stem cells (hPSC)-derived Müllerian duct-like cells (MDLCs) using a defined and effective protocol. The MDLCs are bi-potent, can gradually differentiate into endometrial epithelial and stromal cells, and reconstitute full-thickness endometrium in vitro and in vivo. Furthermore, MDLCs showed the in situ repair capabilities of reconstructing endometrial structure and recovering pregnancy function in full-thickness endometrial injury rats, and their differentiation fate was revealed by single-cell RNA sequencing (scRNA-seq). Our study provides a strategy for hPSC differentiation into endometrial lineages and an alternative seed cell for injured endometrial regeneration.
Keywords	Medicine ; R
Subject code	571
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dissecting the chromosome-level genome of the Asian Clam (Corbicula fluminea)

Tongqing Zhang / Jiawen Yin / Shengkai Tang / Daming Li / Xiankun Gu / Shengyu Zhang / Weiguo Suo / Xiaowei Liu / Yanshan Liu / Qicheng Jiang / Muzi Zhao / Yue Yin / Jianlin Pan

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract The Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve, which is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is rich in protein, amino acids, and microelements. The genome of ... ...

Abstract	Abstract The Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve, which is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is rich in protein, amino acids, and microelements. The genome of C. fluminea has not yet been characterized; therefore, genome-assisted breeding and improvements cannot yet be implemented. In this work, we present a de novo chromosome-scale genome assembly of C. fluminea using PacBio and Hi-C sequencing technologies. The assembled genome comprised 4728 contigs, with a contig N50 of 521.06 Kb, and 1,215 scaffolds with a scaffold N50 of 70.62 Mb. More than 1.51 Gb (99.17%) of genomic sequences were anchored to 18 chromosomes, of which 1.40 Gb (92.81%) of genomic sequences were ordered and oriented. The genome contains 38,841 coding genes, 32,591 (83.91%) of which were annotated in at least one functional database. Compared with related species, C. fluminea had 851 expanded gene families and 191 contracted gene families. The phylogenetic tree showed that C. fluminea diverged from Ruditapes philippinarum, ~ 228.89 million years ago (Mya), and the genomes of C. fluminea and R. philippinarum shared 244 syntenic blocks. Additionally, we identified 2 MITF members and 99 NLRP members in C. fluminea genome. The high-quality and chromosomal Asian Clam genome will be a valuable resource for a range of development and breeding studies of C. fluminea in future research.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Haoyu Wu / Zhi Peng / Ying Xu / Zixuan Sheng / Yanshan Liu / Youguo Liao / Yin Wang / Ya Wen / Junzhi Yi / Chang Xie / Xuri Chen / Jiajie Hu / Bingqian Yan / Huijing Wang / Xudong Yao / Wei Fu / Hongwei Ouyang

Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-

2022 Volume 15

Abstract: Abstract Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the ... ...

Abstract	Abstract Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings ...
Keywords	modRNA ; IGF-1 ; Adipose derived stem cells ; Gene delivery ; Osteoarthritis ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	610 ; 616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HAX1-dependent control of mitochondrial proteostasis governs neutrophil granulocyte differentiation

Yanxin Fan / Marta Murgia / Monika I. Linder / Yoko Mizoguchi / Cong Wang / Marcin Łyszkiewicz / Natalia Ziȩtara / Yanshan Liu / Stephanie Frenz / Gabriela Sciuccati / Armando Partida-Gaytan / Zahra Alizadeh / Nima Rezaei / Peter Rehling / Sven Dennerlein / Matthias Mann / Christoph Klein

The Journal of Clinical Investigation, Vol 132, Iss

2022 Volume 9

Abstract: The relevance of molecular mechanisms governing mitochondrial proteostasis to the differentiation and function of hematopoietic and immune cells is largely elusive. Through dissection of the network of proteins related to HCLS1-associated protein X-1, we ...

Abstract	The relevance of molecular mechanisms governing mitochondrial proteostasis to the differentiation and function of hematopoietic and immune cells is largely elusive. Through dissection of the network of proteins related to HCLS1-associated protein X-1, we defined a potentially novel functional CLPB/HAX1/(PRKD2)/HSP27 axis with critical importance for the differentiation of neutrophil granulocytes and, thus, elucidated molecular and metabolic mechanisms underlying congenital neutropenia in patients with HAX1 deficiency as well as bi- and monoallelic mutations in CLPB. As shown by stable isotope labeling by amino acids in cell culture (SILAC) proteomics, CLPB and HAX1 control the balance of mitochondrial protein synthesis and persistence crucial for proper mitochondrial function. Impaired mitochondrial protein dynamics are associated with decreased abundance of the serine-threonine kinase PRKD2 and HSP27 phosphorylated on serines 78 and 82. Cellular defects in HAX1–/– cells can be functionally reconstituted by HSP27. Thus, mitochondrial proteostasis emerges as a critical molecular and metabolic mechanism governing the differentiation and function of neutrophil granulocytes.
Keywords	Cell biology ; Immunology ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses

Maryam Ghalandary / Yue Li / Thomas Fröhlich / Thomas Magg / Yanshan Liu / Meino Rohlfs / Sebastian Hollizeck / Raffaele Conca / Tobias Schwerd / Holm H. Uhlig / Philip Bufler / Sibylle Koletzko / Aleixo M. Muise / Scott B. Snapper / Fabian Hauck / Christoph Klein / Daniel Kotlarz

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 12

Abstract: Abstract NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy revealed a rare homozygous missense mutation in the ...

Abstract	Abstract NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy revealed a rare homozygous missense mutation in the first CARD domain of NOD2 (ENST00000300589; c.160G > A, p.E54K). Biochemical assays confirmed impaired NOD2-dependent signaling and proinflammatory cytokine production in patient’s cells and heterologous cellular models with overexpression of the NOD2 mutant. Immunoprecipitation-coupled mass spectrometry unveiled the ATPase valosin-containing protein (VCP) as novel interaction partner of wildtype NOD2, while the binding to the NOD2 variant p.E54K was abrogated. Knockdown of VCP in coloncarcinoma cells led to impaired NF-κB activity and IL8 expression upon MDP stimulation. In contrast, tunicamycin-induced ER stress resulted in increased IL8, CXCL1, and CXCL2 production in cells with knockdown of VCP, while enhanced expression of these proinflammatory molecules was abolished upon knockout of NOD2. Taken together, these data suggest that VCP-mediated inflammatory responses upon ER stress are NOD2-dependent.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Seasonal dynamics of photosynthetic activity of Microcystis, genotype abundances and microcystin concentrations in Meiliang Bay, Lake Taihu

Li, Daming / Cuilan Duan / Liqiang Zhong / Shengkai Tang / Tongqing Zhang / Xiaowei Liu / Yanshan Liu

Ecological Society of China Acta ecologica Sinica. 2017 Oct., v. 37, no. 5

2017

Abstract: Lake Taihu is the third largest freshwater lake (surface area: 2338km2, mean depth: 1.9m) in eastern China, and it is also the primary drinking water source for 30 million residents in the lake basin. In recent decades, Lake Taihu has annually ... ...

Abstract	Lake Taihu is the third largest freshwater lake (surface area: 2338km2, mean depth: 1.9m) in eastern China, and it is also the primary drinking water source for 30 million residents in the lake basin. In recent decades, Lake Taihu has annually experienced lake-wide cyanobacterial blooms. However, the seasonal changes of photosynthetic activity of Micricystis, genotype abundances and microcystin and their relationship with environmental factors are still poorly understood. In the present study, surface water samples in Meiliang Bay were collected monthly from January to December in the year of 2014, at the same time, we investigated the photosynthetic activity of Micricystis, the abundances of total and toxic Microcystis genotypes, and microcystins (MCs) concentrations using pulse amplitude modulation (PAM), quantitative real-time PCR (qPCR), and high performance liquid chromatography (HPLC) techniques, respectively. It was found that the maximum and effective quantum yields both had an obvious seasonal patterns. In winter season, photosynthetic activity were not detectable, Then, it increased fast from spring to summer, at the last, it gradually decreased from fall to winter. The level of non-photochemical quenching (NPQ) increased from March to August, when it showed a maximum, decreasing thereafter toward December. The abundances of total and toxic Microcystis genotypes ranged from 1.91±0.15×105 to 8.64±0.56×107, from 2.38±0.25×104 to 5.67±0.43×106copies/mL, respectively, meanwhile, the toxic proportion ranged from 12.5±1.3 to 65.6±3.8%, and they all showed similar change patterns with increasing first and then decreasing later. The extacellular and intracellular MCs concentrations varied from 0.17±0.05 to 1.82±0.35μg/L, from 0.59±0.18 to 14.36±1.62μg/L, respectively. The correlation analysis suggested that photosynthetic capacity and NPQ of Microcystis had positive correlation with water temperature. Meanwhile, there were strong positive correlation among the total and toxic Microcystis genotypes, toxic proportion and intracellular MCs, and they were significant positively correlated with water temperature. In addition, intracellular MCs also have strong positive correlation with total phosphorus. In conclusion, the photosynthetic activity of Microcystis was corresponded to the dynamics of Microcystis bloom, and water temperature may be a key environmental factor which determined Microcystis photosynthetic activity, total and toxic Microcystis genotypes abundances as well as intracellular MCs in Lake Taihu.
Keywords	correlation ; drinking water ; environmental factors ; freshwater lakes ; genotype ; high performance liquid chromatography ; microcystins ; Microcystis ; phosphorus ; photosynthesis ; quantitative polymerase chain reaction ; seasonal variation ; spring ; summer ; surface area ; surface water ; toxicity ; water temperature ; watersheds ; winter ; China
Language	English
Dates of publication	2017-10
Size	p. 284-289.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2233694-1
ISSN	1872-2032 ; 1000-0933
ISSN (online)	1872-2032
ISSN	1000-0933
DOI	10.1016/j.chnaes.2017.02.012
Database	NAL-Catalogue (AGRICOLA)

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