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Antibiotic resistance and its correlation with biofilm formation and virulence genes in Klebsiella pneumoniae isolated from wounds. 从伤口分离的肺炎克雷伯氏菌的抗生素耐药性及其与生物膜形成和毒力基因的相关性。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-20 DOI: 10.1007/s13353-024-00893-w
Mohammed Allami, Eman Jassim Mohammed, Zainab Alnaji, Salsabil A Jassim

Klebsiella pneumoniae is the most important species of the Klebsiella genus and often causes hospital infections. These bacteria have a high resistance to most of the available drugs, which has caused concern all over the world. In this study, we investigated the antibiotic resistance profile and the ability to produce extended-spectrum beta-lactamase (ESBL) among K. pneumoniae isolates, and then we investigated the relationship between these two factors with biofilm formation and the prevalence of different virulence genes. In this study, 130 isolates of K. pneumoniae isolated from wounds were investigated. The antibiotic resistance of the isolates was evaluated by the disk diffusion method. The microtiter plate method was used to measure biofilm formation. The prevalence of virulence genes was detected by multiplex PCR. Among the examined isolates, 85.3% showed multidrug resistance. 87.6% of the isolates were ESBL-positive. Imipenem, meropenem, and fosfomycin were the most effective drugs. The ability of the isolates to produce biofilm was strong (80%), moderate (12.3%), and weak (7.6%), respectively. fimH, mrKD, entB, and tolC virulence genes were observed in all isolates. High prevalence of antibiotic resistance (especially multidrug resistance), high prevalence of ESBL-producing isolates, the ability of all isolates to biofilm formation, and the presence of fimH, mrKD, entB, and tolC virulence genes in all isolates show the importance of these factors in the pathogenesis of K. pneumoniae isolates in Iraq.

肺炎克雷伯菌是克雷伯菌属中最重要的菌种,经常引起医院感染。这些细菌对大多数现有药物都有很强的耐药性,这引起了全世界的关注。在本研究中,我们调查了肺炎克雷伯菌分离株的抗生素耐药性概况和产生广谱β-内酰胺酶(ESBL)的能力,然后研究了这两个因素与生物膜形成和不同毒力基因的流行之间的关系。本研究调查了从伤口中分离出的 130 株肺炎克雷伯菌。采用磁盘扩散法评估了分离株的抗生素耐药性。微孔板法用于测量生物膜的形成。多重 PCR 检测了毒力基因的流行情况。在受检的分离株中,85.3%表现出多药耐药性。87.6%的分离株为 ESBL 阳性。亚胺培南、美罗培南和磷霉素是最有效的药物。在所有分离株中都观察到了 fimH、mrKD、entB 和 tolC 毒力基因。抗生素耐药性(尤其是多药耐药性)的高流行率、产ESBL分离株的高流行率、所有分离株形成生物膜的能力以及所有分离株中存在的fimH、mrKD、entB和tolC毒力基因表明了这些因素在伊拉克肺炎克雷伯菌分离株发病机制中的重要性。
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引用次数: 0
Genetic diversity and population structure of Uganda cassava germplasm. 乌干达木薯种质的遗传多样性和种群结构。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-16 DOI: 10.1007/s13353-024-00892-x
Karoline Leonard Sichalwe, Ismail Kayondo, Richard Edema, Isaac O Dramadri, Emmanuel AAdjei, Heneriko Kulembeka, Wilson Kimani, Doreen Mgonja, Patrick Rubahaiyo, Edward Kanju

Cassava (Manihot esculenta Crantz) holds significant economic importance globally. Evaluating a diverse range of germplasm based on molecular characteristics not only enhances its preservation but also supports its utilization in breeding programs. In this study, we assessed genetic diversity and population structure among 155 cassava genotypes from Uganda using 5247 single nucleotide polymorphism (SNP) markers. Genotyping by sequencing (GBS) was employed for SNP discovery and to evaluate genetic diversity and population structure using the ADMIXTURE software. The cassava accessions comprised two populations: 49 accessions from Ugandan lines and 106 accessions resulting from crosses between South American and Ugandan lines. The average call rate of 96% was utilized to assess marker polymorphism. Polymorphic information content values of the markers ranged from 0.1 to 0.5 with an average of 0.4 which was moderately high. The principal component analysis (PCA) showed that the first two components captured ~ 24.2% of the genetic variation. The average genetic diversity was 0.3. The analysis of molecular variance (AMOVA) indicated that 66.02% and 33.98% of the total genetic variation occurred within accessions and between sub-populations, respectively. Five sub-populations were identified based on ADMIXTURE structure analysis (K = 5). Neighbor-joining tree and hierarchical clustering tree revealed the presence of three different groups which were primarily based on the source of the genotypes. The results suggested that there was considerable genetic variation among the cassava genotypes which is useful in cassava improvement and conservation efforts.

木薯(Manihot esculenta Crantz)在全球具有重要的经济价值。根据分子特征评估多种多样的种质不仅能加强对其的保护,还能支持其在育种计划中的利用。在这项研究中,我们利用 5247 个单核苷酸多态性(SNP)标记评估了乌干达 155 种木薯基因型的遗传多样性和种群结构。通过测序基因分型(GBS)发现了 SNP,并使用 ADMIXTURE 软件评估了遗传多样性和种群结构。木薯品种包括两个群体:其中 49 个来自乌干达品系,106 个来自南美和乌干达品系杂交。平均调用率为 96%,用于评估标记的多态性。标记的多态信息含量值从 0.1 到 0.5 不等,平均值为 0.4,属于中等偏上水平。主成分分析(PCA)显示,前两个成分捕获了约 24.2%的遗传变异。平均遗传多样性为 0.3。分子方差分析(AMOVA)表明,总遗传变异的 66.02% 和 33.98% 分别发生在种内和亚群之间。根据 ADMIXTURE 结构分析(K = 5),确定了五个亚群。邻接树和分层聚类树显示存在三个不同的群体,主要基于基因型的来源。结果表明,木薯基因型之间存在相当大的遗传变异,这有助于木薯的改良和保护工作。
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引用次数: 0
Genotype-environment interaction for grain yield in maize (Zea mays L.) using the additive main effects and multiplicative interaction (AMMI) model. 利用加性主效应和乘性交互作用(AMMI)模型分析玉米(Zea mays L.)谷物产量的基因型与环境交互作用。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-08-08 DOI: 10.1007/s13353-024-00899-4
Jan Bocianowski, Kamila Nowosad, Dariusz Rejek

Genotype-environment interaction consists of the different response of individual genotypes resulting from changing environmental conditions. Its significance is a phenomenon that makes the breeding process very difficult. On the one hand, the breeder expects stable genotypes, i.e., yielding similarly regardless of environmental conditions. On the other hand, selecting the best genotypes for each region is one of the key challenges for breeders and farmers. The aim of this study was to evaluate genotype-by-environment interaction for grain yield in new maize hybrids developed by Plant Breeding Smolice Co. Ltd., utilizing the additive main effects and multiplicative interaction (AMMI) model. The investigation involved 69 maize (Zea mays L.) hybrids, tested across five locations in a randomized complete block design with three replications. Grain yield varied from 8.76 t ha-1 (SMH_16417 in Smolice) to 16.89 t ha-1 (SMH_16043 in Płaczkowo), with a mean yield of 13.16 t ha-1. AMMI analysis identified significant effects of genotype, environment, and their interaction on grain yield. Analysis of variance indicated that 25.12% of the total variation in grain yield was due to environment factor, 35.20% to genotypic differences, and 21.18% to genotype by environmental interactions. Hybrids SMH_1706 and SMH_1707 are recommended for further breeding programs due to their high stability and superior average grain yield.

基因型与环境的交互作用包括个体基因型对不断变化的环境条件的不同反应。这一现象的重要性给育种工作带来了很大困难。一方面,育种者希望基因型稳定,即无论环境条件如何,产量都相似。另一方面,为每个地区选择最佳基因型是育种者和农民面临的主要挑战之一。本研究的目的是评估植物育种斯莫里斯有限公司(Plant Breeding Smolice Co.该研究利用加性主效应和乘性交互作用(AMMI)模型,对植物育种斯莫里斯有限公司开发的玉米杂交种的谷物产量进行了基因型与环境的交互作用评估。调查涉及 69 个玉米(Zea mays L.)杂交种,在五个地点进行了试验,采用随机完全区组设计,三次重复。谷物产量从 8.76 吨/公顷(斯莫利兹的 SMH_16417)到 16.89 吨/公顷(普瓦茨科沃的 SMH_16043)不等,平均产量为 13.16 吨/公顷。AMMI 分析表明,基因型、环境及其交互作用对谷物产量有显著影响。方差分析表明,在谷物产量的总变异中,环境因素占 25.12%,基因型差异占 35.20%,基因型与环境的交互作用占 21.18%。由于杂交种 SMH_1706 和 SMH_1707 具有较高的稳定性和优异的平均谷物产量,因此推荐用于进一步的育种计划。
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引用次数: 0
Importance and variability of the paternal component in sow reproductive traits. 母猪繁殖性状中父系成分的重要性和变异性
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-18 DOI: 10.1007/s13353-024-00910-y
G Cieleń, E Sell-Kubiak

Reproductive traits are an integral part of the goals of the breeding programs that contribute to the economic success of production. Reproductive phenotypes such as litter size, number of piglets born alive, or litter weight at birth are mainly attributed to females. Thus, the maternal components can be found by default in quantitative genetics' animal models. Still, paternal contribution to variance components should not be discarded. In this review, we indicate the importance of paternal effects in pig breeding by describing both the biology and genetics of boars' traits, the use of (non-)genetic service sire effects in quantitative genetic models for traits measured on females, and genes involved in male reproduction. We start by describing the important biological traits of boars that have the most important effect on their reproductive abilities, i.e., sexual maturity, sperm quality, and testes parameters. Then we move to the possible environmental effects that could affect those traits of boars (e.g., feed, temperature). The main part of the review in detail describes the genetics of boars' reproductive traits (i.e., heritability) and their direct effect on reproductive traits of females (i.e., genetic correlations). We then move to the use of both genetic and non-genetic service sire effects in quantitative models estimated as their percentage in the total variance of traits, which vary depending on the breed from 1 to 4.5% or from 1 to 2%, respectively. Finally, we focus on the description of candidate genes and confirmed mutations affecting male reproduction success: IGF2, Tgm8, ESR1, ZSWIM7, and ELMO1. In conclusion, the observed variance of paternal effects in female reproduction traits might come from various attributes of boars including biological and genetic aspects. Those attributes of boars should not be neglected as they contribute to the success of female reproductive traits.

繁殖性状是育种计划目标中不可或缺的一部分,有助于生产取得经济效益。繁殖表型如窝产仔数、成活仔猪数或出生窝重等主要归因于雌性。因此,在定量遗传学的动物模型中,母系成分是默认的。然而,父系对变异成分的贡献也不应被抛弃。在这篇综述中,我们通过描述公猪性状的生物学和遗传学、在定量遗传模型中使用(非)遗传服务父系效应来测量雌性性状以及参与雄性繁殖的基因,来说明父系效应在猪育种中的重要性。我们首先介绍对公猪繁殖能力影响最大的重要生物学特征,即性成熟、精子质量和睾丸参数。然后,我们将讨论可能影响公猪这些特征的环境效应(如饲料、温度)。综述的主要部分详细介绍了公猪繁殖性状的遗传学(即遗传率)及其对雌性繁殖性状的直接影响(即遗传相关性)。然后,我们将讨论在定量模型中使用遗传和非遗传辅助父系效应的问题,这些效应在性状总变异中所占的百分比因品种而异,分别为 1% 至 4.5% 或 1% 至 2%。最后,我们重点描述了影响雄性繁殖成功率的候选基因和已证实的突变:IGF2、Tgm8、ESR1、ZSWIM7 和 ELMO1。总之,在雌性繁殖性状中观察到的父系效应差异可能来自公猪的各种属性,包括生物学和遗传学方面。公猪的这些属性不应被忽视,因为它们有助于雌性繁殖性状的成功。
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引用次数: 0
Comparative genome analysis of endophytic Bacillus amyloliquefaciens MR4: a potential biocontrol agent isolated from wild medicinal plant root tissue. 内生淀粉芽孢杆菌 MR4 的比较基因组分析:从野生药用植物根部组织中分离出的潜在生物控制剂。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-30 DOI: 10.1007/s13353-024-00905-9
Kaiying Yang, Xianxing Dai, Zulihumar Maitikadir, Huijiang Zhang, Haiting Hao, Chengcai Yan

In this investigation, 396 endophytic bacterial strains from six indigenous medicinal plant species within the Xinjiang Tumor Peak National Nature Reserve were subjected to screening. The strain MR4 emerged as a noteworthy contender, demonstrating pronounced biocontrol capabilities coupled with exceptional cold tolerance. Through morphological scrutiny and comprehensive genomic sequencing, MR4 was identified as Bacillus amyloliquefaciens. Antagonistic assays revealed MR4's efficacy in suppressing the causative agents of cotton wilt and verticillium wilt, achieving inhibition rates surpassing 50%. Analyses, underpinned by PCR methodologies, indicated MR4's capacity to biosynthesize a minimum of eight distinct antimicrobial agents. The whole-genome sequencing data indicated that B. amyloliquefaciens MR4 had the genome size and GC content of 4,017,872 bp and 47.14%, respectively, and 4191 coding genes were identified. The genome consists of a single chromosome and one plasmid. Moreover, it was augmented by annotations from various databases, including GO, KEGG, and COG. The pathogenicity of MR4 undergoes evaluation, while predictions concerning MR4's secondary metabolites have disclosed gene clusters for 13 varieties of these compounds, with particular emphasis on surfactins and fengycin. Comparative analyses with four paradigmatic strains shed light on MR4's genomic composition and its phylogenetic lineage within the Bacillus genus. The genomic data pertaining to MR4 have been duly submitted to the NCBI GenBank, bearing the accession numbers CP146236 (Chr1) and CP146237 (plas1). This study endeavors to furnish potent microbial resources for the biocontrol and enhancement of plant growth, thereby providing a theoretical groundwork for MR4's agronomic utilization.

在这项调查中,对来自新疆土默峰国家级自然保护区内六种本地药用植物的 396 株内生细菌进行了筛选。菌株MR4表现出明显的生物防治能力和超强的耐寒性,成为值得关注的竞争者。通过形态学检查和全面的基因组测序,MR4 被鉴定为淀粉芽孢杆菌。拮抗试验显示,MR4 在抑制棉花枯萎病和轮纹枯萎病病原菌方面具有显著功效,抑制率超过 50%。以 PCR 方法为基础的分析表明,MR4 能够生物合成至少八种不同的抗菌剂。全基因组测序数据表明,淀粉芽孢杆菌 MR4 的基因组大小和 GC 含量分别为 4,017,872 bp 和 47.14%,共鉴定出 4191 个编码基因。基因组由一条染色体和一个质粒组成。此外,它还得到了来自各种数据库(包括 GO、KEGG 和 COG)的注释的补充。对 MR4 的致病性进行了评估,同时对 MR4 的次级代谢物进行了预测,发现了 13 种这些化合物的基因簇,其中特别强调了表面活性剂和芬吉素。与四个典型菌株的比较分析揭示了 MR4 的基因组组成及其在芽孢杆菌属中的系统发育系。有关 MR4 的基因组数据已正式提交给 NCBI GenBank,登录号为 CP146236(Chr1)和 CP146237(plas1)。这项研究旨在为生物防治和促进植物生长提供有效的微生物资源,从而为 MR4 的农艺应用提供理论基础。
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引用次数: 0
Transcript level of telomerase reverse-transcriptase (TERT) gene in the rainbow trout (Oncorhynchus mykiss) eggs with different developmental competence for gynogenesis. 雌核发育能力不同的虹鳟鱼卵中端粒酶逆转录酶(TERT)基因的转录水平。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-26 DOI: 10.1007/s13353-024-00887-8
Konrad Ocalewicz, Marcin Kuciński, Igor Jasielczuk, Artur Gurgul, Mirosław Kucharski, Stefan Dobosz

Expression of the telomerase reverse-transcriptase (TERT) gene and activity of telomerase have been reported in the somatic tissues and gonads in fish irrespective of their age and size. Nevertheless, little is known about TERT expression in the fish eggs. In the current study, the presence of the TERT transcripts was confirmed in the rainbow trout ovulated eggs before and after activation with nonirradiated and UV-irradiated (gynogenesis) sperm. Eggs originating from eight females had high and comparable quality expressed by similar hatching rates. However, survival of the gynogenetic larvae that hatched from eggs activated with UV-irradiated sperm and further exposed to the high hydrostatic pressure (HHP) shock for duplication of the maternal chromosomes varied between females from 2.1 ± 0.4 to 40.5 ± 2.2%. Increased level of TERT transcripts was observed in eggs originating from two females, and gametes from only one of them showed improved competence for gynogenesis (27.3 ± 1.9%). In turn, eggs from the female that exhibited the highest survival after gynogenetic activation were characterized by the lowest expression of the TERT gene. Telomerase in rainbow trout eggs may compensate erosion of the telomeres during early embryonic development; however, its upregulation does not assure better development after gynogenetic activation.

据报道,端粒酶逆转录酶(TERT)基因的表达和端粒酶的活性存在于鱼类的体组织和性腺中,与鱼类的年龄和大小无关。然而,人们对鱼卵中TERT的表达却知之甚少。在本研究中,我们证实了虹鳟排卵的鱼卵在使用非辐照精子和紫外线辐照精子(雌核发生)活化之前和之后存在TERT转录本。来自八条雌性虹鳟的卵子质量很高,孵化率相似。然而,用紫外线辐射精子激活的卵孵化出的雌核发育幼虫的存活率在不同雌性之间存在差异,从 2.1 ± 0.4 到 40.5 ± 2.2% 不等。在来自两只雌虫的卵子中观察到 TERT 转录物水平的增加,其中只有一只雌虫的配子显示出较高的雌核发育能力(27.3 ± 1.9%)。反过来,雌核发育激活后存活率最高的雌鱼的卵子中,TERT基因的表达量最低。虹鳟鱼卵中的端粒酶可以补偿胚胎早期发育过程中端粒的侵蚀;但是,端粒酶的上调并不能保证雌核发育激活后虹鳟鱼卵的发育更好。
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引用次数: 0
Peptidylprolyl isomerase D circular RNA sensitizes breast cancer to trastuzumab through remodeling HER2 N4-acetylcytidine modification. 肽基脯氨酰异构酶D环形RNA通过重塑HER2 N4-乙酰胞苷修饰,使乳腺癌对曲妥珠单抗敏感。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-10 DOI: 10.1007/s13353-024-00840-9
Shengting Wang, Qian Li, Yufang Wang, Xiaoming Li, Xinghua Feng, Yuxuan Wei, Jiaman Wang, Xin Zhou

Human epidermal growth factor receptor 2 (HER2) overexpression and activation are crucial for trastuzumab resistance in HER2-positive breast cancer; however, the potential regulatory mechanism of HER2 is still largely undetermined. In this study, a novel circular RNA derived from peptidylprolyl isomerase D (PPID) is identified as a negative regulator of trastuzumab resistance. Circ-PPID is highly stable and significantly downregulated in trastuzumab-resistant cells and tissues. Restoration of circ-PPID markedly enhances HER2-positive breast cell sensitivity to trastuzumab in vitro and in vivo. Circ-PPID directly binds to N-acetyltransferase 10 (NAT10) in the nucleus and blocks the interaction between NAT10 and HER2 mRNA, reducing N4-acetylcytidine (ac4C) modification on HER2 exon 25, leading to HER2 mRNA decay. Intriguingly, the subcellular localization of circ-PPID differs between trastuzumab-sensitive and -resistant cells. Circ-PPID in trastuzumab-resistant cells is located more in the cytoplasm, mainly due to the upregulation of Exportin 4 (XPO4), which results in the loss of spatial conditions for circ-PPID to bind to nuclear NAT10. Taken together, our data suggest that circ-PPID is a previously unappreciated ac4C-dependent HER2 epigenetic regulator, providing a promising therapeutic direction for overcoming trastuzumab resistance in clinical setting.

人类表皮生长因子受体 2(HER2)的过度表达和激活是 HER2 阳性乳腺癌产生曲妥珠单抗耐药性的关键;然而,HER2 的潜在调控机制在很大程度上仍未确定。在这项研究中,一种源自肽基脯氨酰异构酶D(PPID)的新型环状RNA被鉴定为曲妥珠单抗耐药性的负调控因子。circ-PPID在曲妥珠单抗耐药细胞和组织中高度稳定并显著下调。在体外和体内,circ-PPID 的恢复可显著增强 HER2 阳性乳腺细胞对曲妥珠单抗的敏感性。circ-PPID直接与细胞核中的N-乙酰转移酶10(NAT10)结合,阻断NAT10与HER2 mRNA之间的相互作用,减少HER2第25外显子上的N4-乙酰胞苷(ac4C)修饰,导致HER2 mRNA衰减。有趣的是,circ-PPID在曲妥珠单抗敏感细胞和抗性细胞中的亚细胞定位有所不同。曲妥珠单抗耐药细胞中的 circ-PPID 更多位于细胞质中,这主要是由于 Exportin 4 (XPO4) 的上调导致 circ-PPID 失去了与核 NAT10 结合的空间条件。综上所述,我们的数据表明,circ-PPID是一种以前未被认识到的依赖于ac4C的HER2表观遗传调控因子,为克服临床上曲妥珠单抗耐药提供了一个很有前景的治疗方向。
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引用次数: 0
Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa. 基因编辑细胞:治疗大疱性表皮松解症的新型异体基因/细胞疗法。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-03-09 DOI: 10.1007/s13353-024-00839-2
Fatemeh Gila, Vahab Alamdari-Palangi, Maedeh Rafiee, Arezoo Jokar, Sajad Ehtiaty, Aria Dianatinasab, Seyyed Hossein Khatami, Mortaza Taheri-Anganeh, Ahmad Movahedpour, Jafar Fallahi

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

大疱性表皮松解症(EB)是一组罕见的遗传性皮肤脆弱症,具有遗传性。这些疾病与至少 16 个编码表皮粘附复合体成分的基因突变有关。目前,这种疾病还没有有效的治疗方法。目前所有的治疗方法都侧重于局部治疗,以预防并发症和感染。近年来,通过临床前和临床研究的进展,在治疗严重遗传性皮肤水疱病(EB)方面取得了重大进展。蛋白质疗法和细胞疗法(如异体干细胞移植)取得了可喜的进展;此外,基于 RNA 的疗法和基因疗法也已成为现实。从胚胎或成人组织(包括皮肤)获得的干细胞是未分化细胞,具有生成、维持和替代发育完全的细胞和组织的能力。临床前和临床研究的最新进展大大提高了干细胞疗法的效果,为目前医学疗法无法有效治疗的各种疾病提供了一种前景广阔的治疗方案。不同类型的干细胞(主要是造血干细胞和间充质干细胞)可用于治疗严重的疾病,每种干细胞都有一些有益的效果。此外,大量研究表明,针对异体和自体表皮干细胞的基因转移方法很有希望取代或纠正有缺陷的基因。这些方法可以使 EB 患者的原发性角质形成细胞再生并恢复粘附性。通过移植由基因纠正的自体表皮干细胞产生的皮肤移植物,对少数患者的皮肤病变进行长期治疗已显示出良好的效果。本文试图总结细胞疗法治疗 EB 的现状、潜在发展前景以及相关挑战。
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引用次数: 0
Cannabidiol (CBD) modulates the transcriptional profile of ethanol-exposed human dermal fibroblast cells. 大麻二酚(CBD)可调节暴露于乙醇的人类真皮成纤维细胞的转录谱。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1007/s13353-024-00915-7
Artur Gurgul, Jakub Żurowski, Tomasz Szmatoła, Mirosław Kucharski, Sebastian Sawicki, Ewelina Semik-Gurgul, Ewa Ocłoń

Cannabidiol (CBD) is abundant in the Cannabis sativa plant and exhibits complex immunomodulatory, anxiolytic, antioxidant, and antiepileptic properties. Several studies suggest that CBD could be used for different purposes in alcohol use disorder (AUD) and alcohol-related injuries to the brain and the liver. In this study, we focused on analyzing transcriptional alterations in human dermal fibroblasts (HDFs) cell line challenged simultaneously with ethanol and CBD as an ethanol-protective agent. We aimed to expose the genes and pathways responsible for at least some of the CBD effects in those cells that can be related to the AUD. Transcriptome analysis was performed using HDFs cell line that expresses both cannabinoid receptors and can metabolize ethanol through alcohol dehydrogenase activity. Fibroblasts are also responsible for the progression of liver fibrosis, a common comorbidity in AUD. With the use of a cellular test, we found that CBD at the lowest applied concentration (0.75 μM) was able to stimulate depressed metabolism and reduce the level of apoptosis of cells treated with different concentrations of ethanol to the level observed in the control cells. Similar observations were made at the transcriptome level, in which cells treated with ethanol and CBD had similar expression profiles to the control cells. CBD also affects several genes connected with extracellular matrix formation (especially its collagen constituent), which can have potential implications for, e.g., fibrosis process.

大麻二酚(CBD)在大麻植物中含量丰富,具有复杂的免疫调节、抗焦虑、抗氧化和抗癫痫特性。多项研究表明,CBD 可用于治疗酒精使用障碍(AUD)以及与酒精相关的大脑和肝脏损伤。在本研究中,我们重点分析了同时受到乙醇和作为乙醇保护剂的 CBD 挑战的人真皮成纤维细胞(HDFs)细胞系的转录变化。我们的目的是揭示在这些细胞中至少有哪些基因和通路负责CBD的影响,这些基因和通路可能与AUD有关。我们使用 HDFs 细胞系进行了转录组分析,该细胞系同时表达大麻素受体,并能通过乙醇脱氢酶活性代谢乙醇。成纤维细胞也是造成肝纤维化进展的原因,而肝纤维化是 AUD 的常见合并症。通过使用细胞测试,我们发现最低应用浓度(0.75 μM)的 CBD 能够刺激抑制代谢,并将使用不同浓度乙醇处理的细胞的凋亡水平降低到对照细胞中观察到的水平。在转录组水平上也有类似的观察结果,用乙醇和 CBD 处理过的细胞与对照细胞有相似的表达谱。CBD 还会影响与细胞外基质(尤其是其胶原成分)形成有关的几个基因,这可能会对纤维化过程等产生潜在影响。
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引用次数: 0
Single-cell integrated transcriptomics reveals the role of keratinocytes in head and neck squamous cell carcinoma. 单细胞综合转录组学揭示了角质形成细胞在头颈部鳞状细胞癌中的作用。
IF 2 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-29 DOI: 10.1007/s13353-024-00842-7
Shaokun Liu, Meng Lian, Boxuan Han, Jugao Fang, Zhenlin Wang

Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignant tumor with significant morbidity and mortality. Understanding the molecular mechanisms of HNSCC and identifying prognostic markers and therapeutic targets are crucial for improving patient outcomes. In this study, we utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to comprehensively analyze HNSCC at the cellular level. We identified keratinocytes as the predominant cell type in tumor samples, suggesting their potential role in HNSCC development. Through hdWGCNA co-expression network analysis, we identified gene modules associated with HNSCC progression. Furthermore, we constructed a prognostic model based on specific genes and demonstrated its robust predictive performance in multiple datasets. The model exhibited strong correlations with immune cell infiltration patterns and signaling pathways related to tumor progression. Additionally, drug sensitivity analysis revealed potential chemotherapeutic targets for HNSCC treatment. Our findings provide valuable insights into the molecular characteristics and immune microenvironment of HNSCC, offering new perspectives for prognosis prediction and therapeutic interventions in clinical practice. Further research is warranted to validate and expand upon these findings, ultimately improving patient outcomes in HNSCC.

头颈部鳞状细胞癌(HNSCC)是一种发病率和死亡率都很高的常见恶性肿瘤。了解 HNSCC 的分子机制、确定预后标志物和治疗靶点对改善患者预后至关重要。在这项研究中,我们利用单细胞 RNA 测序(scRNA-seq)和大容量 RNA-seq 数据在细胞水平上对 HNSCC 进行了全面分析。我们发现角质形成细胞是肿瘤样本中最主要的细胞类型,这表明角质形成细胞在 HNSCC 的发展过程中扮演着潜在的角色。通过 hdWGCNA 共表达网络分析,我们发现了与 HNSCC 进展相关的基因模块。此外,我们还构建了一个基于特定基因的预后模型,并在多个数据集中证明了其强大的预测性能。该模型与肿瘤进展相关的免疫细胞浸润模式和信号通路有很强的相关性。此外,药物敏感性分析揭示了 HNSCC 治疗的潜在化疗靶点。我们的研究结果为了解 HNSCC 的分子特征和免疫微环境提供了有价值的见解,为临床实践中的预后预测和治疗干预提供了新的视角。有必要开展进一步的研究来验证和扩展这些发现,最终改善 HNSCC 患者的预后。
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引用次数: 0
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Journal of Applied Genetics
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