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The lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA network inhibits cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy. lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA网络抑制肥厚性阻塞性心肌病的心肌细胞肥厚。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.105
Bangrong Song, Wei Li, Xiaoyu Xu, Haiming Dang, Ran Dong

Hypertrophic obstructive cardiomyopathy (HOCM) is a well-recognized inherited cardiac disease. This study was conducted to explore the role of lncRNA ADAMTS9 antisense RNA 1 (ADAMTS9-AS1) in HOCM-induced cardiomyocyte hypertrophy. The serum of HOCM patients was collected. AC16 cells were treated with isoproterenol (ISO) and transfected with oe-ADAMTS9-AS1 vector, miR-185-5p mimic, and lysine acetyltransferase 7 (KAT7) specific small interfering RNA. lncRNA ADAMTS9-AS1, miR-185-5p, KAT7, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in the serum or cells were determine by qRT-PCR or Western blot assay. Cell surface area was observed by Texas Red-Phalloidin staining. Subcellular localization of lncRNA ADAMTS9-AS1 was tested by nuclear/cytoplasmic fractionation assay, with RNA pull-down and dual-luciferase assay to validate gene interactions. lncRNA ADAMTS9-AS1 was downregulated in the serum of HOCM patients and ISO-treated AC16 cells. lncRNA ADAMTS9-AS1 overexpression inhibited ISO-induced cardiomyocyte hypertrophy and reduced levels of ANP and BNP. lncRNA ADAMTS9- AS1 was located in cytoplasm and inhibited miR-185-5p expression through targeted binding. miR-185-5p bound to KAT7 3'UTR and inhibited KAT7 expression. miR-185-5p overexpression and KAT7 knockdown both neutralized the inhibitory role of lncRNA ADAMTS9-AS1 in cardiomyocyte hypertrophy. Overall, lncRNA ADAMTS9-AS competitively bound to miR-185-5p to up-regulate KAT7 and thus inhibited cardiomyocyte hypertrophy.

肥厚性阻塞性心肌病(HOCM)是一种公认的遗传性心脏病。本研究旨在探讨lncRNA ADAMTS9反义RNA 1 (ADAMTS9- as1)在hocm诱导心肌细胞肥厚中的作用。采集HOCM患者血清。用异丙肾上腺素(ISO)处理AC16细胞,并用e- adamts9 - as1载体、miR-185-5p模拟物和赖氨酸乙酰转移酶7 (KAT7)特异性小干扰RNA转染。采用qRT-PCR或Western blot检测血清或细胞中的lncRNA ADAMTS9-AS1、miR-185-5p、KAT7、脑钠肽(BNP)、房钠肽(ANP)。采用Texas Red-Phalloidin染色法观察细胞表面积。采用核/细胞质分离法检测lncRNA ADAMTS9-AS1的亚细胞定位,采用RNA下拉和双荧光素酶法验证基因相互作用。在HOCM患者和iso处理的AC16细胞的血清中,lncRNA ADAMTS9-AS1下调。lncRNA ADAMTS9-AS1过表达抑制iso诱导的心肌细胞肥大,降低ANP和BNP水平。lncRNA ADAMTS9- AS1位于细胞质中,通过靶向结合抑制miR-185-5p的表达。miR-185-5p结合KAT7 3'UTR并抑制KAT7的表达。miR-185-5p过表达和KAT7敲低均可中和lncRNA ADAMTS9-AS1在心肌细胞肥厚中的抑制作用。总体而言,lncRNA ADAMTS9-AS竞争性地结合miR-185-5p上调KAT7,从而抑制心肌细胞肥大。
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引用次数: 1
Protective effects of hachimijiogan (HJG), a Japanese Kampo medicine, on cancer cachectic muscle wasting in mice. 日本贡布药八味丸对小鼠癌症恶病质性肌肉萎缩的保护作用。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.199
Satoshi Kametaka, Mari Isobe, Kenshin Komata, Makoto Morinaga, Kazuma Nagahata, Sachiko Lee-Hotta, Yasushi Uchiyama, Masahiro Shibata, Hideshi Sugiura

Myogenesis is required to generate skeletal muscle tissue and to maintain skeletal muscle mass. Decreased myogenesis under various pathogenic conditions results in muscular atrophy. Through a small screening of Japanese traditional (Kampo) medicines, hachimijiogan (HJG) was shown to promote the myogenic differentiation of C2C12 myoblasts through the upregulation of myogenin. In tumor-bearing cancer-cachectic mice, HJG was also found to have a protective effect against cancer-cachectic muscle wasting. This effect was significant when HJG was administered in combination with aerobic exercise by treadmill running. Moreover, HJG ameliorated the cellular atrophy of C2C12 myotubes induced by treatment with conditioned medium derived from a colon-26 cancer cell culture. In addition, HJG suppressed H2O2-dependent myotube atrophy, suggesting that HJG could reverse the atrophic phenotypes by eliminating reactive oxygen species.

肌生成是生成骨骼肌组织和维持骨骼肌质量所必需的。在各种致病条件下,肌生成减少会导致肌肉萎缩。通过对日本传统药物(Kampo)的小规模筛选,八重肌甘(HJG)显示出通过上调肌生成素来促进C2C12成肌细胞的肌源性分化。在荷瘤的癌症疼痛小鼠中,也发现HJG对癌症疼痛肌肉萎缩具有保护作用。当HJG与跑步机跑步的有氧运动相结合时,这种效果是显著的。此外,HJG改善了由来源于结肠-26癌症细胞培养物的条件培养基处理诱导的C2C12肌管的细胞萎缩。此外,HJG抑制H2O2依赖性肌管萎缩,表明HJG可以通过消除活性氧来逆转萎缩表型。
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引用次数: 0
Immunohistochemical characterization of the mandibular condyle for type I and II collagen, aggrecan, MMP-9, and MMP-13 in MMP-2-deficient mice. mmp -2缺陷小鼠下颌髁I型和II型胶原蛋白、聚集蛋白、MMP-9和MMP-13的免疫组织化学表征
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.65
Mu-Chen Yang, Megumi Nakamura, Miyuki Mayanagi, Yasuyuki Sasano

Mice devoid of matrix metalloproteinase (MMP)-2 due to gene targeting have been reported to show articular cartilage destruction in the knee joint; however, the phenotype of the mandibular condylar cartilage remains unknown. Thus, in the present study, we investigated the mandibular condyle in Mmp2-/- mice. We obtained and bred Mmp2-/- mice from the same source as the previous study, and performed genotyping using genomic DNA extracted from finger snips. The mandibular condyle of Mmp2-/- mice and wild-type (WT) mice was immunohistochemically examined for the localization of extracellular matrix (ECM) proteins (type I and II collagen, and aggrecan), and MMP-9 and MMP-13. No cartilage destruction was observed in the mandibular condyle of Mmp2-/- mice, and no difference was found in the localization of the ECM proteins between the Mmp2-/- mice and WT mice. However, the bone marrow cavity in the subchondral bone of the mandibular condyle was more distinct in Mmp2-/- mice than in WT mice at the age of 50 weeks. Of note, MMP-9 characteristically localized in multinucleated cells in the mandibular condyle in 50-week-old Mmp2-/- mice. MMP-2 may be involved in the regulation of osteoclast differentiation and the formation of the bone marrow cavity in aged mice.

据报道,由于基因靶向而缺乏基质金属蛋白酶(MMP)-2的小鼠在膝关节显示关节软骨破坏;然而,下颌髁软骨的表型仍然是未知的。因此,在本研究中,我们研究了Mmp2-/-小鼠的下颌髁。我们从与先前研究相同的来源获得并繁殖了Mmp2-/-小鼠,并使用从手指剪中提取的基因组DNA进行基因分型。免疫组织化学检测Mmp2-/-小鼠和野生型(WT)小鼠下颌髁的细胞外基质(ECM)蛋白(I型和II型胶原蛋白和聚集蛋白)和MMP-9和MMP-13的定位。Mmp2-/-小鼠下颌髁未见软骨破坏,ECM蛋白的定位在Mmp2-/-小鼠和WT小鼠之间无差异。然而,在50周龄时,Mmp2-/-小鼠下颌髁软骨下骨的骨髓腔比WT小鼠更明显。值得注意的是,在50周龄的Mmp2-/-小鼠中,MMP-9特征性地定位于下颌髁的多核细胞中。MMP-2可能参与老龄小鼠破骨细胞分化和骨髓腔形成的调控。
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引用次数: 0
A point of view on human fat olfaction - do fatty derivatives serve as cues for awareness of dietary fats? 关于人类脂肪嗅觉的观点——脂肪衍生物是否可以作为对膳食脂肪认知的线索?
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.127
Satoshi Tsuzuki

Fat (triglycerides) consumption is critical for the survival of animals, including humans. Being able to smell fat can be advantageous in judging food value. However, fat has poor volatility; thus, olfaction of fat seems impossible. What about fatty acids that comprise fat? Humans smell and discriminate medium-chain fatty acids. However, no conclusive evidence has been provided for the olfactory sense of long-chain fatty acids, including essential acids such as linoleic acid (LA). Instead, humans likely perceive the presence of essential fatty acids through the olfaction of volatile compounds generated by their oxidative breakdown (e.g., hexanal and γ-decalactone). For some people, such scents are pleasing, especially when they come from fruit. Nonetheless, it remains unclear whether the olfaction of these volatiles leads to the recognition of fat per se. Nowadays, people often smell LA-borne aldehydes such as E,E-2,4-decadienal that occur appreciably, for example, from edible oils during deep frying, and are pronely captivated by their characteristic "fatty" note, which can be considered a "pseudo-perception" of fat. However, our preference for such LA-borne aldehyde odors may be a potential cause behind the modern overdose of n-6 fatty acids. This review aims to provide a view of whether and, if any, how we olfactorily perceive dietary fats and raises future purposes related to human fat olfaction, such as investigating sub-olfactory systems for detecting long-chain fatty acids.

脂肪(甘油三酯)的消耗对包括人类在内的动物的生存至关重要。能够闻到脂肪在判断食物价值时是有利的。然而,脂肪的波动性较差;因此,脂肪的嗅觉似乎是不可能的。那组成脂肪的脂肪酸呢?人类能闻到并辨别中链脂肪酸。然而,长链脂肪酸,包括必需酸,如亚油酸(LA)的嗅觉尚未提供确凿的证据。相反,人类可能通过氧化分解产生的挥发性化合物(如己醛和γ-癸内酯)的嗅觉来感知必需脂肪酸的存在。对一些人来说,这样的气味令人愉悦,尤其是来自水果的气味。然而,尚不清楚这些挥发物的气味是否会导致对脂肪本身的识别。如今,人们经常闻到诸如E,E-2,4-十二烯醛之类的LA-borne醛类,例如,在油炸过程中从食用油中明显产生,并且很容易被它们特有的“脂肪”气味所吸引,这可以被认为是对脂肪的“伪感知”。然而,我们对这种la基醛气味的偏好可能是现代n-6脂肪酸过量的潜在原因。这篇综述的目的是提供一个观点,如果有的话,我们是如何嗅觉感知膳食脂肪的,并提出未来与人类脂肪嗅觉相关的目的,如研究亚嗅觉系统来检测长链脂肪酸。
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引用次数: 0
Anatomical basis of gastrin- and CCK-secreting cells and their functions. A review. 胃泌素和cck分泌细胞的解剖基础及其功能。复习一下。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.81
Toshihiko Iwanaga

Gastrin and CCK (cholecystokinin), gut hormones first secreted after postprandial stages, share the C-terminal amino acids and some types of receptors to be stimulated. Both types of hormone-secreting cells are typical open-type cells which detect foods and their digested elements in the lumen and regulate the secretion of gastric acid and digestive enzymes, gut motility, and satiety. Gastrin cell granules are characterized by their heterogenous ultrastructure within the cell, while CCK cell granules show a uniform ultrastructural figure. Gastrin cells are equipped with peptone receptor GPR92, amino acid receptor GPRC6A, and a Ca-sensing receptor. In addition to nutrient receptors, the release of CCK is regulated by a unique negative feedback mechanism. Development of an antibody for CCK-specific receptor (CCK-1R) has revealed its exact localization throughout the body, but specific antibodies against CCK-2R remain unavailable. Gastrin affects differentiation and proliferation-including cancer cells, while CCK possesses trophic effects to target tissues. CCK is a peripheral satiety signal and acts either via the vagus or directly on the dorsal medulla via CCK-1R. In this review, endocrine cells secreting these unique and so-called old gut hormones are described on a morphological basis.

胃泌素和CCK(胆囊收缩素)是在餐后阶段首先分泌的肠道激素,它们共享c端氨基酸和一些类型的受体来刺激。这两种类型的激素分泌细胞都是典型的开放式细胞,它们检测食物及其在腔内的消化成分,调节胃酸和消化酶的分泌,肠道运动和饱腹感。胃泌素细胞颗粒的超微结构具有异质性,而CCK细胞颗粒的超微结构呈均匀状。胃泌素细胞具有蛋白胨受体GPR92、氨基酸受体GPRC6A和钙感应受体。除了营养受体外,CCK的释放还受到一种独特的负反馈机制的调节。针对cck特异性受体(CCK-1R)的抗体的开发已经揭示了其在全身的确切定位,但针对CCK-2R的特异性抗体仍然不可用。胃泌素影响分化和增殖,包括癌细胞,而CCK对靶组织具有营养作用。CCK是一种外周饱腹感信号,通过迷走神经或直接通过CCK- 1r作用于髓质背侧。在这篇综述中,内分泌细胞分泌这些独特的和所谓的古老的肠道激素在形态学基础上进行了描述。
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引用次数: 2
Cannabinoid receptors involved in descending inhibition on spinal seizure-like activity in the phrenic output. 大麻素受体参与下降抑制脊髓癫痫样活动在膈输出。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.41
Shih Tien Lin, Makito Iizuka, Yoshihiro Mikami, Shunya Yoda, Hiroshi Onimaru, Masahiko Izumizaki

Seizure-like burst activities are induced by blockade of GABAA and/or glycine receptors in various spinal ventral roots of brainstem-spinal cord preparation from neonatal rodents. We found that this is not applicable to the phrenic nerve and that a new inhibitory descending pathway may suppress seizure-like activity in the phrenic nerve. Experiments were performed in brainstem-spinal cord preparation from newborn rats (age: 0-1 day). Left phrenic nerve and right C4 activities were recorded simultaneously. When GABAA and glycine receptors were blocked by 10 μM bicuculline and 10 μM strychnine (Bic+Str), seizure-like burst activities appeared in the fourth cervical ventral root (C4) but not the phrenic nerve. After making a transverse section at C1, the inspiratory burst activity disappeared from both C4 and the phrenic nerve, whereas seizure-like activity appeared in both nerves. We hypothesized that inhibitory descending pathways other than those via GABAA and/or glycine receptors (from the medulla to the spinal cord) work to avoid disturbance of regular respiratory-related diaphragm contraction by seizure-like activity. We found that cannabinoid receptor antagonist, AM251 was effective for the induction of seizure-like activity by Bic+Str in the phrenic nerve in brainstem-spinal cord preparation. Cannabinoid receptors may be involved in this descending inhibitory system.

在新生啮齿类动物的脑干-脊髓制备中,阻断GABAA和/或甘氨酸受体可诱导癫痫样爆发活动。我们发现这并不适用于膈神经,而一种新的抑制性下降通路可能抑制膈神经的癫痫样活动。实验采用新生大鼠(0-1日龄)的脑干-脊髓制备。同时记录左膈神经和右膈神经C4活动。10 μM双管碱和10 μM士的宁(Bic+Str)阻断GABAA和甘氨酸受体后,第四颈腹根(C4)出现癫痫样爆发活动,膈神经未出现。在C1处作横切面后,C4和膈神经的吸气爆发活动均消失,而两种神经均出现癫痫样活动。我们假设除了通过GABAA和/或甘氨酸受体(从髓质到脊髓)的抑制性下降途径外,抑制性下降途径可以避免癫痫样活动对正常呼吸相关膈肌收缩的干扰。我们发现大麻素受体拮抗剂AM251对脑干-脊髓制备中膈神经Bic+Str诱导癫痫样活动有效。大麻素受体可能参与了这种下降抑制系统。
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引用次数: 1
GP2-expressing cells: a new guardian with divergent functions in the intestine, eyes, and nose. 表达gp2的细胞:在肠道、眼睛和鼻子中具有不同功能的新守护者。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.233
Toshihiko Iwanaga, Shunsuke Kimura

GP (glycoprotein)-2, originally identified as a predominant membranous component of pancreatic acinar cells, has attracted the interest of researchers in mucosal immunology for its role as a functional molecule specific for antigen-sampling cells in the intestinal Peyer's patches. GP2 is involved in the detection of pathological bacteria and is also histologically useful for the identification of the M cell lineage and their differentiation in lymphoid tissues. Subsequent immunohistochemistry for GP2 has revealed a broad distribution of M cells and related cells in the nasopharyngeal lymphoid tissues, conjunctiva, tear duct, and airway. Especially, GP2 cells in the paranasal sinuses and tear duct have been identified as novel types of epithelial cells. The systematic administration of RANKL can induce extra-M cells in conventional epithelia of body. The production and release of GP2 by conjunctival goblet cells and several mucous glands suggests leading roles for mucous cells in protection, including the entrapment of microorganisms for infections. The ocular surface and conjunctiva are connected to the lacrimal sac, nasolacrimal duct, and further nasal cavity, comprising another canal that passes through the body. The broad distribution of GP2-expressingcells may indicate its function as a new guardian in the intestine, eyes, and nose, all of which are exposed to external milieu.

GP(糖蛋白)-2,最初被认为是胰腺腺泡细胞的主要膜性成分,由于其作为肠道Peyer's补丁中抗原取样细胞的功能性分子的作用,引起了粘膜免疫学研究人员的兴趣。GP2参与病理细菌的检测,在组织学上对淋巴组织中M细胞谱系及其分化的鉴定也很有用。随后的GP2免疫组化显示M细胞及相关细胞广泛分布于鼻咽淋巴组织、结膜、泪管和气道。特别是鼻窦和泪管中的GP2细胞已被确定为新型上皮细胞。系统给药RANKL可诱导机体常规上皮细胞产生m外细胞。结膜杯状细胞和几个黏液腺产生和释放GP2表明黏液细胞在保护中起主要作用,包括为感染捕获微生物。眼表和结膜与泪囊、鼻泪管和进一步的鼻腔相连,构成另一条穿过身体的通道。gp2表达细胞的广泛分布可能表明其在暴露于外界环境的肠道、眼睛和鼻子中具有新的守护者功能。
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引用次数: 0
Comparative analysis of tumor content estimation methods based on simu- lated tumor samples identified their impact on somatic variant detection in cancer whole genome sequencing. 比较分析了基于模拟肿瘤样本的肿瘤含量估计方法,确定了它们对肿瘤全基因组测序中体细胞变异检测的影响。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.161
Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Keiichi Ohshima, Masakuni Serizawa, Keiichi Hatakeyama, Sumiko Ohnami, Shumpei Ohnami, Akane Naruoka, Yasue Horiuchi, Akira Iizuka, Koji Maruyama, Yasuto Akiyama, Ken Yamaguchi

Whole genome sequencing (WGS) in cancer genomics has become widespread with recent technological innovations, and the amount and types of information obtained from WGS are increasing rapidly. Appropriate interpretation of results is becoming increasingly important in clinical applications. This study aimed to evaluate the accuracy of tumor content estimation and its impact on somatic variant detection, using 100 simulated tumor samples covering 10-100% tumor content constructed from the sequencing data of cell line models. Extensive analysis revealed that the estimation results varied among computational analytical methods. Notably, there was a large discrepancy in low tumor content (≤ 30%). The reproducibility decreased in cases wherein chromosome-scale copy number changes were observed in normal cells. The minimum tumor content required to detect somatic alterations was estimated to be 10-30%. Identification of whole genome doubling was achieved with the lowest tumor content, followed by single nucleotide variation/insertion or deletion, structural variation, and copy number variation. Tumor content had a significantly higher impact on the false negatives than the false positives in variant calls. Results should be interpreted cautiously for samples wherein tumor content is a concern. These results can form the basis of developing important guidelines for evaluating cancer WGS.

随着近年来的技术创新,全基因组测序(WGS)在癌症基因组学中的应用越来越广泛,从WGS中获得的信息数量和类型也在迅速增加。结果的合理解释在临床应用中变得越来越重要。本研究旨在评估肿瘤含量估计的准确性及其对体细胞变异检测的影响,利用细胞系模型测序数据构建了100个模拟肿瘤样本,覆盖10-100%的肿瘤含量。广泛的分析表明,不同计算分析方法的估计结果存在差异。值得注意的是,低肿瘤含量(≤30%)差异较大。在正常细胞中观察到染色体规模拷贝数变化的情况下,可重复性降低。检测体细胞改变所需的最低肿瘤含量估计为10-30%。以最低的肿瘤含量鉴定全基因组加倍,其次是单核苷酸变异/插入或删除、结构变异和拷贝数变异。在变异呼叫中,肿瘤含量对假阴性的影响显著高于假阳性。结果应谨慎解释样本,其中肿瘤内容是一个问题。这些结果可以为制定评估癌症WGS的重要指南奠定基础。
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引用次数: 0
The effect of the formalin-fixed paraffin-embedded process on salivary microbiota profiling. 福尔马林固定石蜡包埋工艺对唾液微生物群谱的影响。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.117
Hiroto Sano, Takuichi Sato, Yoriaki Kanri, Junya Ono, Yasuo Okada

In recent years, bacterial DNA in formalin-fixed paraffin-embedded (FFPE) samples has been recognized as a valuable bioresource for microbiota studies. This study aimed to examine the effect of the FFPE process on microbiota profiling to evaluate whether FFPE samples could serve as an alternative bioresource to fresh samples in oral microbiota studies. Fresh saliva was collected from nine subjects. The pellets obtained by centrifuging the collected saliva were fixed in formalin, then dehydrated and embedded in paraffin to prepare FFPE samples. The abundance of the hypervariable regions V1-9, V1-2, and V3-4 of the 16S rRNA gene in fresh and FFPE samples was relatively compared. In addition, microbiota profiling was performed to compare the results between the two sample types. The results showed that the FFPE process resulted in a certain degree of fragmentation of the 16S rRNA gene. However, the V1-2 region was relatively well-preserved compared to the V1-9 and V3-4 regions, suggesting that short regions are suitable targets for oral microbiota analysis. Importantly, there were no significant differences in alpha and beta diversity of microbiota between fresh and FFPE samples, and microbiota profiles were similar between the two sample types, suggesting that FFPE samples could be a valuable bioresource for oral microbiota studies.

近年来,福尔马林固定石蜡包埋(FFPE)样品中的细菌DNA已被认为是微生物群研究的宝贵生物资源。本研究旨在研究FFPE工艺对微生物群分析的影响,以评估FFPE样品是否可以作为口腔微生物群研究中新鲜样品的替代生物资源。收集了9名受试者的新鲜唾液。将收集的唾液离心得到的微球固定在福尔马林中,脱水后包埋石蜡,制备FFPE样品。比较新鲜和FFPE样品中16S rRNA基因高变区V1-9、V1-2和V3-4的丰度。此外,进行微生物群分析以比较两种样品类型之间的结果。结果表明,FFPE过程导致16S rRNA基因出现一定程度的断裂。然而,与V1-9和V3-4区域相比,V1-2区域保存相对较好,这表明短区域是口腔微生物群分析的合适靶点。重要的是,新鲜和FFPE样品之间的微生物群α和β多样性没有显著差异,两种样品类型之间的微生物群谱相似,这表明FFPE样品可能是口腔微生物群研究的宝贵生物资源。
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引用次数: 0
3-Iodothyronamine, a trace amine-associated receptor agonist, regulates intracellular Ca2+ increases via CaMK II through Epac2 in rat cerebral arterioles. 3-碘甲状腺胺是一种微量胺相关受体激动剂,通过大鼠脑小动脉中的Epac2通过CaMK II调节细胞内Ca2+的增加。
IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.2220/biomedres.44.219
Wakana Sakanoue, Takuya Yokoyama, Masato Hirakawa, Satsuki Maesawa, Kenichi Sato, Tomoyuki Saino

Trace amines (TAs) in the nervous system bind to TA-associated receptors (TAARs) and are involved in the regulation of monoaminergic functions. Among TAAR subtypes, TAAR1 has been implicated in the development of neurological disorders, such as schizophrenia. The present study investigated the effects of the TAAR1 agonist, 3-iodothyronamine (T1AM) on cerebral arterioles using fluctuations in the intracellular concentration of Ca2+ ([Ca2+]i) as an index of contractile responses. In cerebral arterioles, most of the TAAR agonists did not increase [Ca2+]i, while only T1AM elevated [Ca2+]i in vascular smooth muscle cells. This increase involved extracellular Ca2+ influx through T-type Ca2+ channels and inositol trisphosphate- and ryanodine-receptor-mediated Ca2+ release from intracellular stores. The inhibition of the cAMP sensor, exchange protein directly activated by cAMP (Epac) 2, and calmodulin kinase (CaMK) II strongly inhibited Ca2+ elevations. The present study revealed that T1AM acted not only on the TAAR1 receptor as previously suggested, but also on other G-protein coupled receptors and/or signal transduction systems to increase intracellular Ca2+ in cerebral arteriole smooth muscle cells. These results suggest that when using T1AM in clinical practice, attention should be paid to the early rise in blood pressure.

神经系统中的微量胺(TA)与TA相关受体(TAARs)结合,并参与单胺能功能的调节。在TAAR亚型中,TAAR1与神经系统疾病的发展有关,如精神分裂症。本研究利用细胞内Ca2+([Ca2+]i)浓度的波动作为收缩反应的指标,研究了TAAR1激动剂3-碘甲状腺胺(T1AM)对脑小动脉的影响。在脑小动脉中,大多数TAAR激动剂没有增加血管平滑肌细胞的[Ca2+]i,而只有T1AM升高了血管平滑肌细胞中的[Ca2++]i。这种增加涉及通过T型Ca2+通道的细胞外Ca2+内流,以及肌醇三磷酸和赖氨酸受体介导的细胞内储存的Ca2+释放。cAMP传感器、由cAMP(Epac)2直接激活的交换蛋白和钙调蛋白激酶(CaMK)II的抑制强烈抑制Ca2+升高。本研究表明,T1AM不仅如前所述作用于TAAR1受体,还作用于其他G蛋白偶联受体和/或信号转导系统,以增加脑小动脉平滑肌细胞中的细胞内Ca2+。这些结果表明,在临床实践中使用T1AM时,应注意血压的早期升高。
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引用次数: 1
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Biomedical Research-tokyo
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