IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-05 DOI: 10.1016/j.gene.2024.148982

Ding Gong , Ni Jian , Yu-Tong Zhou, Jie Wang

Background

The CT143 protein of Chlamydia trachomatis (Ct) is a key immunodominant antigen and candidate type-III secretion substrate. Although CT143 expression has not been detected in the cytosol of infected cells, it is known to interfere with the physiological behavior of HeLa cells. This study aims to investigate how the CT143 protein affects the protein expression profile of HeLa cells, providing a basis for further research into Ct’s pathogenic mechanisms.

Methods

We constructed a stably transfected HeLa cell line, pCD513B-1-CT143-HeLa, and a control cell line, pCD513B-1-HeLa. Protein expression profiles of these cell lines were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins were identified, constructed into a database, and verified using parallel reaction monitoring (PRM). Bioinformatics software facilitated the preliminary analysis of the biological functions of these differential proteins.

Results

A total of 221 host proteins were differentially expressed, with 68 upregulated and 153 downregulated. These variations influence the regulation of peptidase activity and are crucial in biological processes such as cell secretion and protease activity. Significant changes were noted in protein processing, alcohol dehydrogenase activity, Aldo-Keto reductase activity, and peptidase regulator activity. Furthermore, alterations were observed in cellular components like the plasma membrane and cell periphery. Pathways involving the hematopoietic system, glycosaminoglycan degradation, retinol metabolism, and cytochrome P450-mediated exogenous drug metabolism were notably affected. Indirect interactions among differentially expressed proteins included three key nodal proteins: C3, IFIT3, and IFIT1.

Conclusion

The successful construction of a host differential protein expression profile was achieved through stable transfection of HeLa cells with the CT143 gene. The differential proteins identified are implicated in regulating various biological processes such as intracellular signal transduction, cell secretion, protein processing, hydrolysis, and enzyme activity. These findings suggest that the CT143 protein may influence the host cell’s biological behavior by altering host protein expression, potentially hindering Ct growth and development.

背景：沙眼衣原体（Ct）的 CT143 蛋白是一种关键的免疫显性抗原和候选 III 型分泌底物。虽然 CT143 在受感染细胞的细胞质中未被检测到表达，但已知它会干扰 HeLa 细胞的生理行为。本研究旨在探讨 CT143 蛋白如何影响 HeLa 细胞的蛋白表达谱，为进一步研究 CT 的致病机制提供依据：方法：我们构建了稳定转染的 HeLa 细胞系 pCD513B-1-CT143-HeLa 和对照细胞系 pCD513B-1-HeLa。使用液相色谱-串联质谱法（LC-MS/MS）测定了这些细胞系的蛋白质表达谱。对差异表达的蛋白质进行了鉴定，建立了数据库，并使用平行反应监测（PRM）进行了验证。生物信息学软件有助于对这些差异蛋白的生物功能进行初步分析：结果：共有 221 个宿主蛋白质表达存在差异，其中 68 个上调，153 个下调。这些变化影响了肽酶活性的调节，在细胞分泌和蛋白酶活性等生物过程中至关重要。蛋白质加工、醇脱氢酶活性、醛酮还原酶活性和肽酶调节剂活性都发生了显著变化。此外，质膜和细胞外围等细胞成分也发生了变化。涉及造血系统、糖胺聚糖降解、视黄醇代谢和细胞色素 P450 介导的外源性药物代谢的途径受到明显影响。不同表达蛋白之间的间接相互作用包括三个关键的节点蛋白：C3、IFIT3 和 IFIT1：结论：通过用 CT143 基因稳定转染 HeLa 细胞，成功构建了宿主差异蛋白表达谱。鉴定出的差异蛋白参与调控各种生物过程，如细胞内信号转导、细胞分泌、蛋白质加工、水解和酶活性。这些发现表明，CT143 蛋白可能会通过改变宿主蛋白的表达来影响宿主细胞的生物学行为，从而可能阻碍 Ct 的生长和发育。

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引用次数: 0

miRNAs in umbilical Wharton’s jelly in neonates with different birth weights: A pilot study 不同出生体重新生儿脐带沃顿果冻中的 miRNA：一项试验性研究。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-05 DOI: 10.1016/j.gene.2024.148984

Cristina García-Muro , Cristina Toledo-Gotor , Sara Pasamón-García , María de Pablo-de las Heras , Eduardo Esteban-Zubero , María Yolanda Ruiz del Prado , Elena Domínguez-Garrido

Background

Birth weight is a critical indicator of perinatal health. miRNAs are small non-coding RNA molecules, ranging from 18 to 25 nucleotides in length, that regulate gene expression. Specific miRNAs have been implicated in metabolic pathways influencing fetal growth, and their dysregulation may contribute to variations in birth weight. Our objective was to isolate amplifiable miRNAs from umbilical cord tissue and compare their expression across three patient groups.

Methods

The study sample comprised 23 patients: 8 small for gestational age (SGA), 10 large for gestational age (LGA), and 5 appropriate for gestational age (AGA). Umbilical cord tissue samples were collected immediately after childbirth, stored, and subsequently processed. The miRNA expression profile of these samples was analyzed using high-throughput sequencing, and the results were evaluated through bioinformatic analysis.

Results

We identified significant differences in the expression levels of 6 miRNAs. miR-324-3p was downregulated in SGA compared to both AGA and LGA groups. Conversely, miR-337-3p was upregulated in LGA compared to both SGA and AGA. miR-760 was downregulated in LGA relative to SGA and AGA, while miR-4707-3p, miR-548a-3p, and miR-6733-5p were upregulated in both SGA and LGA compared to AGA. Most of these miRNAs appear to be associated with the transforming growth factor-beta signaling pathway.

Conclusions

This exploratory study suggests that miRNA expression in umbilical cord tissue is associated with birth weight. Notably, the downregulation of miR-324-3p in SGA newborns indicates that its decreased expression may be related to SGA conditions.

背景：出生体重是围产期健康的重要指标：出生体重是围产期健康的一个重要指标。miRNA 是长度为 18 至 25 个核苷酸的非编码 RNA 小分子，可调控基因表达。特定的 miRNA 与影响胎儿生长的代谢途径有关，它们的失调可能会导致出生体重的变化。我们的目的是从脐带组织中分离出可扩增的 miRNA，并比较它们在三组患者中的表达情况：研究样本包括 23 名患者：方法：研究样本包括 23 名患者：8 名小胎龄（SGA）、10 名大胎龄（LGA）和 5 名适龄（AGA）。脐带组织样本在分娩后立即采集、储存，随后进行处理。利用高通量测序技术分析了这些样本的 miRNA 表达谱，并通过生物信息学分析对结果进行了评估：与 AGA 和 LGA 组相比，SGA 组的 miR-324-3p 表达下调。相反，与 SGA 和 AGA 相比，miR-337-3p 在 LGA 中上调。与 SGA 和 AGA 相比，miR-760 在 LGA 中下调，而与 AGA 相比，miR-4707-3p、miR-548a-3p 和 miR-6733-5p 在 SGA 和 LGA 中上调。这些miRNA中的大多数似乎与转化生长因子-β信号通路有关：这项探索性研究表明，脐带组织中 miRNA 的表达与出生体重有关。值得注意的是，miR-324-3p 在 SGA 新生儿中的下调表明，它的表达减少可能与 SGA 状况有关。

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引用次数: 0

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-05 DOI: 10.1016/j.gene.2024.148985

Wen Wang , Yunjia Jiao , Xiaojing Du , Zhaoming Ye

Osteosarcoma is the most common primary bone malignancy, with a very poor prognosis. Aberrant glycosylation is close involvement in osteosarcoma. Accordingly, this study aimed at investigating the role of glycosylation genes in the prognosis and therapy options of osteosarcoma. The microenvironment of osteosarcoma was assessed using estimate algorithm. A total of 20 immune-related glycosylation genes (IRGGs) was identified using Pearson correlation analysis. Accordingly, osteosarcoma patients were divided into C1 and C2 type using consensus clustering. Multiple algorithms (Xcell, MCP-counter, ssGSEA, epic, quantiseq), cancer immune cycle analysis, and GSVA were applied to estimate the immune, molecule and metabolism characteristics of osteosarcoma, indicating that C1 type was featured with high immune infiltration, high glycosylation, enriched MEK signaling, and good prognosis, while C2 type was characterized by more metastasis, enriched immunotherapy-positive gene signatures, high tumor mutation burden, and poor prognosis. Results from TIDE algorithm and immunotherapy datasets suggested the C2 type’s preference of immune checkpoint inhibitors (ICIs), while data of GDSC, CMap analysis and cell experiments indicated that C1 type was sensitivity to MEK inhibitor PD0325901. In addition, univariate Cox and Lasso analysis was combined to establish an IRGGs’ risk score containing 6 genes (B3GNT8, FUT7, GAL3ST4, GALNT14, HS3ST2, and MFNG). The data of DCA and ROC indicated its well prediction of prognosis in osteosarcoma. Finally, cellular location analysis showed that the 6 genes not only distributed in tumor cells but also in immune cells. In summary, the classification and risk score based on IRGGs effectively predicted the prognosis and therapy options of osteosarcoma. Further studies on IRGGs may contribute to the understanding of cancer immunity in osteosarcoma.

骨肉瘤是最常见的原发性骨恶性肿瘤，预后极差。骨肉瘤与糖基化异常关系密切。因此，本研究旨在探讨糖基化基因在骨肉瘤预后和治疗方案中的作用。研究采用估计算法评估了骨肉瘤的微环境。通过皮尔逊相关分析，共鉴定出20个免疫相关糖基化基因（IRGGs）。据此，骨肉瘤患者通过共识聚类被分为C1和C2型。应用多种算法（Xcell、MCP-counter、ssGSEA、epic、quantiseq）、癌症免疫周期分析和GSVA估测骨肉瘤的免疫、分子和代谢特征，结果表明C1型骨肉瘤具有高免疫浸润、高糖基化、富含MEK信号和预后好的特点，而C2型骨肉瘤具有多转移、富含免疫治疗阳性基因特征、高肿瘤突变负荷和预后差的特点。TIDE算法和免疫治疗数据集的结果表明，C2型偏好免疫检查点抑制剂（ICIs），而GDSC、CMap分析和细胞实验数据表明，C1型对MEK抑制剂PD0325901敏感。此外，单变量 Cox 分析和 Lasso 分析相结合，建立了包含 6 个基因（B3GNT8、FUT7、GAL3ST4、GALNT14、HS3ST2 和 MFNG）的 IRGGs 风险评分。DCA 和 ROC 的数据表明，它能很好地预测骨肉瘤的预后。最后，细胞定位分析表明，这 6 个基因不仅分布在肿瘤细胞中，也分布在免疫细胞中。总之，基于IRGGs的分类和风险评分能有效预测骨肉瘤的预后和治疗方案。对IRGGs的进一步研究可能有助于了解骨肉瘤的癌症免疫。

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引用次数: 0

Lost in transcription 转录中丢失。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-05 DOI: 10.1016/j.gene.2024.148987

P.G. Sand , V. Rössler

引用次数: 0

Classification, identification, and DNA barcoding study for common cockroach species (Dictyoptera: Blattaria) from China 中国常见蟑螂种类（双翅目：蜚蠊科）的分类、鉴定和 DNA 条形码研究。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-04 DOI: 10.1016/j.gene.2024.148981

Hu Li , Zhang Shangqing , Zhao Yae , Yang Fan , Zhang Xinyue , Liu Shirui , Zhang Tianyi , Niu Dongling

Cockroaches are well-known pests and quarantined organisms worldwide. Due to morphological diversity and a lack of molecular data, their classification and identification are facing challenges. This study performed classification, identification, and DNA barcoding for cockroaches collected from China. Seventy-six samples were morphologically identified as seven species of two superfamilies that included Blattella germanica, Eublaberus posticus and Blaptica dubia belonging to the superfamily Blaberoidea, and Periplaneta americana, Periplaneta lateralis, Periplaneta fuliginosa and Periplaneta australasiae belonging to the superfamily Blattoidea. Based on sequence alignments of nine ribosomal and mitochondrial genes across the order Blattaria retrieved from GenBank, rDNA ITS2-517 bp and mtDNA 16S-327 bp were screened as candidates for molecular identification. Universal primers were designed for PCR amplification, cloning, and sequencing of the 37 representative samples. Sequence alignments and phylogeny analysis showed that both ITS2 and 16S confirmed samples 1–9, 20–24, and 25–29 as B. germanica, P. americana, and P. lateralis, respectively; only 16S (not ITS2) confirmed samples 10–14, 15–19, 30–34, and 35–37 as E. posticus, Blap. dubia, P. fuliginosa, and P. australasiae, respectively, indicating that 16S was a better target than ITS2 for molecular identification of cockroaches. Conservative motif and divergence analysis further revealed that ITS2 sequences vary significantly among different taxa, whereas 16S sequences are relatively conserved. There is an obvious barcoding gap between maximum intraspecific divergence and minimum interspecific divergence (2.57 % vs. 5.62 %) for ITS2, but not for 16S (6.15 % vs. 2.63 %). Therefore, it was confirmed that ITS2 is an ideal DNA barcode for molecular identification of cockroaches at lower category.

蟑螂是世界上众所周知的害虫和检疫生物。由于形态多样性和分子数据的缺乏，蟑螂的分类和鉴定面临着挑战。本研究对从中国采集的蟑螂进行了分类、鉴定和 DNA 条形码编码。76个样本经形态学鉴定为两个超科的7个种，包括隶属于Blaberoidea超科的Blattella germanica、Eublaberus posticus和Blaptica dubia，以及隶属于Blattoidea超科的Periplaneta americana、Periplaneta lateralis、Periplaneta fuliginosa和Periplaneta australasiae。根据从 GenBank 中检索到的 Blattaria 目中 9 个核糖体和线粒体基因的序列比对，筛选出 rDNA ITS2-517 bp 和 mtDNA 16S-327 bp 作为分子鉴定的候选基因。设计了通用引物，用于对 37 个代表性样本进行 PCR 扩增、克隆和测序。序列比对和系统进化分析表明，ITS2 和 16S 均证实样本 1-9、20-24 和 25-29 分别为 B.germanica、P.americana 和 P.lateralis；只有 16S（而非 ITS2）证实样本 10-14、15-19、30-34 和 35-37 分别为 E.posticus、Blap.dubia、P.fuliginosa 和 P.australasiae，表明 16S 是比 ITS2 更好的蟑螂分子鉴定目标。保守模式和差异分析进一步表明，ITS2 序列在不同类群之间存在显著差异，而 16S 序列则相对保守。ITS2 的最大种内差异和最小种间差异之间存在明显的条形码差距（2.57 % vs. 5.62 %），而 16S 则没有这种差距（6.15 % vs. 2.63 %）。因此，ITS2 是低等蟑螂分子鉴定的理想 DNA 条形码。

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引用次数: 0

Soybean gene GmMLP34 regulates Arabidopsis negative response to high temperature stress 大豆基因 GmMLP34 调节拟南芥对高温胁迫的负反馈。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-04 DOI: 10.1016/j.gene.2024.148983

Zhi Xianguan, Lu Yun, Liao Wei, Chen Linying, Chen Haoran, Hu Xiaoyu, Wang Heng, Wei Ying, Wang Xiaobo, Li Jiajia

The functions of major latex proteins (MLPs) in plant defense and stress responses have been widely documented; however, their roles in HT stress response in soybeans have not been elucidated. This study investigated the role of GmMLP34, a member of the major latex protein (MLP) family, in the response of soybeans to HT stress. Transcriptome analysis of HT-resistant (JD21) and HT-sensitive (HD14) soybean leaves under HT stress (43.40 ± 1.70 °C) and field conditions revealed differential expression of GmMLP34. Further examination across different HT-resistant varieties showed that GmMLP34 was down-regulated in the leaves of 6 HT-resistant varieties (85.7 %) and up-regulated in the leaves of 6 HT-sensitive varieties (85.7 %) under the HT treatment (45 °C for 3 h). The results of this study indicate that ectopic expression of the GmMLP34 gene in Arabidopsis led to a significant decrease in the survival rate of seedling when compared to the wild type (WT) under HT stress conditions of 37/28 °C (day/night) for 5 d, Moreover, the results indicated a significant decrease in primary root length and lateral root number under 45 °C/3 h HT stress followed by 12 h room temperature recovery. Additionally, the levels of abscisic acid (ABA), and flavonoids, and the activity of the peroxidase (POD) enzyme in the antioxidant system was decreased, while the activity of the superoxide dismutase (SOD) enzyme increased in GmMLP34-overexpressing transgenic Arabidopsis thaliana. The expression levels of the HT-response genes AtCHS1 and AtCHI2-A, were significantly down-regulated, whereas that of AtGBP1 was significantly up-regulated. These results suggest that GmMLP34 negatively regulates the response of Arabidopsis thaliana to HT stress by modulating flavonoid synthesis, hormone synthesis, and the antioxidant enzyme system. These findings provide theoretical information for the genetic improvement of HT tolerance in soybean and contribute to the understanding of the molecular mechanisms underlying plant responses to abiotic stress.

主要乳胶蛋白（MLPs）在植物防御和胁迫响应中的功能已被广泛记载，但它们在大豆 HT 胁迫响应中的作用尚未阐明。本研究调查了主要乳胶蛋白（MLP）家族成员 GmMLP34 在大豆对 HT 胁迫响应中的作用。在高温胁迫（43.40 ± 1.70 °C）和田间条件下，对抗高温胁迫（JD21）和对高温胁迫敏感（HD14）的大豆叶片进行转录组分析，发现 GmMLP34 的表达存在差异。对不同抗高温胁迫品种的进一步研究表明，在高温胁迫处理（45 °C，3 h）下，6 个抗高温胁迫品种叶片中的 GmMLP34 下调（85.7%），6 个对高温胁迫敏感品种叶片中的 GmMLP34 上调（85.7%）。该研究结果表明，在 37/28 ℃（白天/黑夜）的高温胁迫条件下，拟南芥异位表达 GmMLP34 基因后，与野生型相比，幼苗存活率显著降低，而且在 45 ℃/3 h 高温胁迫后室温恢复 12 h 的条件下，主根长度和侧根数量显著减少。此外，在 GmMLP34 表达的转基因拟南芥中，脱落酸（ABA）和类黄酮的含量以及抗氧化系统中过氧化物酶（POD）的活性都有所下降，而超氧化物歧化酶（SOD）的活性则有所上升。HT 响应基因 AtCHS1 和 AtCHI2-A 的表达水平显著下调，而 AtGBP1 的表达水平显著上调。这些结果表明，GmMLP34通过调节黄酮类化合物合成、激素合成和抗氧化酶系统，负向调节拟南芥对HT胁迫的响应。这些发现为遗传改良大豆对 HT 的耐受性提供了理论信息，并有助于理解植物对非生物胁迫响应的分子机制。

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引用次数: 0

Exploring the effects of naringenin on cell functioning and energy synthesis in the hippocampus of male Wistar rats with chronic tinnitus, by examining genetic indicators such as Bax, Bcl-2, Tfam, and Pgc-1α 通过检测 Bax、Bcl-2、Tfam 和 Pgc-1α 等基因指标，探讨柚皮素对慢性耳鸣雄性 Wistar 大鼠海马细胞功能和能量合成的影响。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-03 DOI: 10.1016/j.gene.2024.148980

Seyede-Mojdeh Safavi-Naeini , Mohammad Nasehi , Mohammad-Reza Zarrindast , Seyed-Abbas Safavi-Naeini

Background

The pivotal factors, including neural plasticity, oxidative stress, neuronal inflammation, and apoptosis, play a significant role in the pathogenesis of tinnitus. The balance between Bax/Bcl-2 genes is an important factor in determining the rate of apoptosis. Pgc-1α and Tfam genes are fundamental regulators of mitochondrial biogenesis. Naringenin possesses significant antioxidant, neuroprotective, anti-inflammatory, anti-apoptotic, and antiviral properties, and its compounds are effective on cell signaling pathways.

Aims

In light of the aforementioned information, we endeavored to evaluate the impact of naringenin on the expression levels of Bax, Bcl-2, Pgc-1α, and Tfam genes in the hippocampus of male Wistar rats with chronic tinnitus.

Material and Methods

To demonstrate the existence of tinnitus, all rats were instructed to complete an “active avoidance test” utilizing a conditioning box. The expression levels of genes mentioned above were assessed using real-time PCR.

Results

The sodium salicylate at a dosage of 350 mg/kg showed an upregulation in the expression level of Bax and a downregulation in the expression level of the Bcl-2 gene (p < 0.001). Furthermore, the sodium salicylate displayed significantly higher expression levels of Tfam and Pgc-1α (p < 0.001) genes. The naringenin, at a dose of 100 mg/kg, led to a decrease in Bax gene expression (p < 0.05) and an increase in Bcl-2 gene expression (p < 0.05). On the other hand, naringenin restored the expression level of both Tfam (p < 0.001) and Pgc-1α (p < 0.01) genes.

Conclusions

Our research findings demonstrate that sodium salicylate-induced tinnitus leads to enhanced apoptosis and mitochondrial biogenesis within the hippocampus. Additionally, our evidence recommends that naringenin can reduce apoptosis effectively and maintain a balanced mitochondrial state.

背景：神经可塑性、氧化应激、神经元炎症和细胞凋亡等关键因素在耳鸣的发病机制中起着重要作用。Bax/Bcl-2 基因之间的平衡是决定细胞凋亡速度的重要因素。Pgc-1α 和 Tfam 基因是线粒体生物生成的基本调节因子。柚皮苷具有显著的抗氧化、神经保护、抗炎、抗凋亡和抗病毒等作用，其化合物对细胞信号通路有效。目的：根据上述信息，我们试图评估柚皮苷对慢性耳鸣雄性Wistar大鼠海马中Bcl-2、Bax、Pgc-1α和Tfam基因表达水平的影响：为了证明耳鸣的存在，所有大鼠都被要求利用条件盒完成 "主动回避测试"。使用实时 PCR 评估上述基因的表达水平：结果：剂量为 350 毫克/千克的水杨酸钠会上调 Bax 基因的表达水平，下调 Bcl-2 基因的表达水平：我们的研究结果表明，水杨酸钠诱导的耳鸣会导致海马内细胞凋亡和线粒体生物生成增强。此外，我们的证据还表明，柚皮素能有效减少细胞凋亡，维持线粒体的平衡状态。

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引用次数: 0

Clinical and prognostic significance of FBXL6 expression in ovarian cancer 卵巢癌中 FBXL6 表达的临床和预后意义。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-03 DOI: 10.1016/j.gene.2024.148978

Dianxin Tao , Shenghan Lou , Wei Huang , Kaidi Sun , Jian Li , Zhiqiang Wang , Yanan Pi , Yue Zhao , Jinglin Wen , Qin Xie , Fanling Meng , Ge Lou

Objective

Growing evidence indicates that F-box and leucine-rich repeat protein 6 (FBXL6) is associated with the progression of various cancers, including gastric cancer, hepatocellular carcinoma, and colorectal cancer. This study focuses on the prognostic significance of FBXL6 in OC.

Methods

Differential levels of FBXL6 in multiple cancers were evaluated using the TCGA and GSE26712 databases. We screened FBXL6-related differentially expressed genes using the GSE63885 dataset and conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis. The genes that associate with FBXL6 were screened using the “limma” package, the STRING database, and Cytoscape software, and the association was validated through Gene Expression Profiling Interactive Analysis. The potential substrates of FBXL6 were predicted using UbiBrowser2.0 database. FBXL6 protein levels in 84 OC samples were evaluated using immunohistochemistry. The prognostic significance of FBXL6 was explored using Kaplan–Meier and Cox regression analyses. Based on the Cox regression results, an FBXL6-based nomogram that can predict the overall survival (OS) rate were constructed. Moreover, we examined the net benefits and discriminative ability of the nomogram using the decision curve analysis (DCA), calibration plots, and receiver operating characteristic (ROC) curve.

Results

FBXL6 was elevated in OC tissues, and the overexpression of FBXL6 was linked to poor prognosis in OC patients. The ROC and DCA curves indicated that the prognostic value of the FBXL6-based nomogram model was superior to that of FBXL6, age, and FIGO stage alone.

Conclusions

Elevated FBXL6 expression was an independent factor for OC, and an easily applied nomogram was developed to predict OS in OC patients.

目的：越来越多的证据表明，F-盒和富含亮氨酸重复蛋白6（FBXL6）与胃癌、肝癌和结直肠癌等多种癌症的进展有关。本研究的重点是 FBXL6 在 OC 中的预后意义：方法：利用 TCGA 和 GSE26712 数据库评估了 FBXL6 在多种癌症中的差异水平。我们利用 GSE63885 数据集筛选了与 FBXL6 相关的差异表达基因，并进行了基因本体和京都基因组百科全书的通路分析。使用 "limma "软件包、STRING 数据库和 Cytoscape 软件筛选与 FBXL6 相关的基因，并通过基因表达谱交互分析验证其关联性。利用 UbiBrowser2.0 数据库预测了 FBXL6 的潜在底物。采用免疫组化方法评估了84个OC样本中的FBXL6蛋白水平。使用 Kaplan-Meier 和 Cox 回归分析探讨了 FBXL6 的预后意义。根据 Cox 回归结果，我们构建了一个基于 FBXL6 的提名图，可以预测总生存率（OS）。此外，我们还利用决策曲线分析（DCA）、校准图和接收器操作特征曲线（ROC）检验了提名图的净效益和鉴别能力：结果：FBXL6在OC组织中升高，FBXL6的过表达与OC患者的不良预后有关。ROC曲线和DCA曲线显示，基于FBXL6的提名图模型的预后价值优于单纯的FBXL6、年龄和FIGO分期：结论：FBXL6表达升高是OC的一个独立因素，研究人员开发了一种易于应用的提名图来预测OC患者的OS。

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引用次数: 0

Downregulation of glucose-energy metabolism via AMPK signaling pathway in granulosa cells of diminished ovarian reserve patients 卵巢储备功能减退患者的颗粒细胞通过 AMPK 信号通路下调葡萄糖能量代谢。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-02 DOI: 10.1016/j.gene.2024.148979

Qinying Zhu , Junhong Du , Yi Li , Xue Qin , Ruifen He , Hao Ma , Xiaolei Liang

Glucose metabolism plays a crucial role in the function of granulosa cells (GCs) and the development of follicles. In cases of diminished ovarian reserve (DOR), alterations in these processes can impact female fertility. This study aims to investigate changes in glucose-energy metabolism in GCs of young DOR patients aged 20 to 35 years and their correlation with the onset and progression of DOR. 72 DOR cases and 75 women with normal ovarian reserve (NOR) as controls were included based on the POSEIDON and Bologna criteria. Samples of GCs and follicular fluid (FF) were collected for a comprehensive analysis involving transcriptomics, metabolomics, RT-qPCR, JC-1 staining, and flow cytometry. The study identified differentially expressed genes and metabolites in GCs of DOR and NOR groups, revealing 7 common pathways related to glucose-energy metabolism, along with 11 downregulated genes and 14 metabolites. Key substances in the glucose-energy metabolism pathway, such as succinate, lactate, NADP, ATP, and ADP, showed decreased levels, with the DOR group exhibiting a reduced ADP/ATP ratio. Downregulation of genes involved in glycolysis (HK, PGK, LDH1), the TCA cycle (CS), and gluconeogenesis (PCK) was observed, along with reduced glucose content and expression of glucose transporter genes (GLUT1 and GLUT3) in DOR GCs. Additionally, decreased AMPK pathway activity and impaired mitochondrial function in DOR suggest a connection between mitochondrial dysfunction and disrupted energy metabolism. Above all, the decline in glucose-energy metabolism in DOR is closely associated with its onset and progression. Reduced glucose uptake and impaired mitochondrial function in DOR GCs lead to internal energy imbalances, hindering the AMPK signaling pathway, limiting energy production and supply, and ultimately impacting follicle development and maturation.

葡萄糖代谢对颗粒细胞（GC）的功能和卵泡的发育起着至关重要的作用。在卵巢储备功能减退（DOR）的情况下，这些过程的改变会影响女性的生育能力。本研究旨在调查 20 至 35 岁年轻 DOR 患者颗粒细胞葡萄糖能量代谢的变化及其与 DOR 发病和进展的相关性。根据 POSEIDON 和博洛尼亚标准，纳入了 72 名 DOR 病例和 75 名卵巢储备功能正常（NOR）的女性作为对照。研究人员采集了GCs和卵泡液（FF）样本，进行了包括转录组学、代谢组学、RT-qPCR、JC-1染色和流式细胞术在内的综合分析。研究发现了 DOR 组和 NOR 组 GC 中表达不同的基因和代谢物，揭示了与葡萄糖能量代谢相关的 7 条共同通路，以及 11 个下调基因和 14 个代谢物。葡萄糖能量代谢途径中的关键物质，如琥珀酸、乳酸、NADP、ATP和ADP的含量均有所下降，其中DOR组的ADP/ATP比值降低。在 DOR 组 GC 中，参与糖酵解（HK、PGK、LDH1）、TCA 循环（CS）和葡萄糖生成（PCK）的基因下调，葡萄糖含量和葡萄糖转运体基因（GLUT1 和 GLUT3）的表达也有所降低。此外，DOR 中 AMPK 通路活性降低和线粒体功能受损表明线粒体功能障碍与能量代谢紊乱之间存在联系。总之，DOR 中葡萄糖能量代谢的下降与 DOR 的发病和进展密切相关。DOR GC 中葡萄糖摄取减少和线粒体功能受损会导致内部能量失衡，阻碍 AMPK 信号通路，限制能量的产生和供应，最终影响卵泡的发育和成熟。

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引用次数: 0

NIPSNAP3A regulates cellular homeostasis by modulating mitochondrial dynamics NIPSNAP3A 通过调节线粒体动力学来调节细胞稳态。

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2024-10-01 DOI: 10.1016/j.gene.2024.148976

Run Yan , Liting Chen , Zimu Cai , Jiyao Tang , Yanlin Zhu , Yanping Li , Xuemin Wang , Yu Ruan , Qi Han

Mitochondria are essential for cell metabolism and survival as they produce the majority of cellular ATP through oxidative phosphorylation as well as regulate critical processes such as cell proliferation and apoptosis. NIPSNAP family of proteins are predominantly mitochondrial matrix proteins. However, the molecular and cellular functions of the NIPSNAPs, particularly NIPSNAP3A, have remained elusive. Here, we demonstrated that NIPSNAP3A knockdown in HeLa cells inhibited their proliferation and migration and attenuated apoptosis induced by Actinomycin D (Act-D). These findings suggested a complex relationship between cellular processes and mitochondrial functions, mediated by NIPSNAP3A. Further investigations revealed that NIPSNAP3A knockdown not only inhibited mitochondrial fission through reduction of DRP1-S616, but also suppressed cytochrome c release in apoptosis. Collectively, our findings highlight the critical role of NIPSNAP3A in coordinating cellular processes, likely through its influence on mitochondrial dynamics.

线粒体对细胞的新陈代谢和存活至关重要，因为它们通过氧化磷酸化产生细胞的大部分 ATP，并调节细胞增殖和凋亡等关键过程。NIPSNAP 蛋白家族主要是线粒体基质蛋白。然而，NIPSNAPs（尤其是 NIPSNAP3A）的分子和细胞功能一直难以捉摸。在这里，我们证明了在 HeLa 细胞中敲除 NIPSNAP3A 可抑制其增殖和迁移，并减轻放线菌素 D（Act-D）诱导的细胞凋亡。这些发现表明，在 NIPSNAP3A 的介导下，细胞过程与线粒体功能之间存在着复杂的关系。进一步研究发现，敲除 NIPSNAP3A 不仅能通过减少 DRP1-S616 抑制线粒体分裂，还能抑制细胞凋亡中细胞色素 c 的释放。总之，我们的研究结果突显了 NIPSNAP3A 在协调细胞过程中的关键作用，这可能是通过其对线粒体动力学的影响实现的。

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