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Theranostic Potential of Bacteriophages against Oral Squamous Cell Carcinoma. 噬菌体对口腔鳞状细胞癌的抗癌潜力
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-05-28 DOI: 10.2174/0115665232305905240521081553
Maheswaran Easwaran, Sivagnanavelmurugan Madasamy, Baskar Venkidasamy

Oral Squamous Cell Carcinoma (OSCC) is a widespread and challenging disease that accounts for 94% of cancers of the oral cavity worldwide. Bacteriophages (phages) have shown promise as a potential theranostic agent for the treatment of OSCC. It may offer advantages in overcoming the challenges of conventional methods. Modern high-throughput pyrosequencing techniques confirm the presence of specific bacterial strains associated with OSCC. Bio-panning and filamentous phages facilitate visualization of the peptide on surfaces and show high affinity in OSCC cells. The peptide has the potential to bind integrin (αvβ6), aid in diagnosis, and inhibit the proliferation of OSCC cells. Mimotopes of tumor-associated antigens show cytotoxic and immune responses against cancer cells. Biomarker-based approaches such as transferrin enable early OSCC diagnosis. A modified temperate phage introduces CRISPR-Cas3 to target antimicrobial-resistant bacteria associated with OSCC. The research findings highlight the evolving field of phage diagnostics and therapy and represent a new avenue for non-invasive, targeted approaches to the detection and treatment of OSCC. However, extensive clinical research is required to validate the efficacy of phages in innovative cancer theranostic strategies.

口腔鳞状细胞癌(OSCC)是一种广泛存在且具有挑战性的疾病,占全球口腔癌的 94%。细菌噬菌体(噬菌体)有望成为治疗口腔鳞状细胞癌的潜在治疗药物。它在克服传统方法的挑战方面可能具有优势。现代高通量热测序技术证实了与 OSCC 相关的特定细菌菌株的存在。生物平移和丝状噬菌体有助于肽在表面的可视化,并在 OSCC 细胞中显示出很高的亲和力。该多肽具有结合整合素(αvβ6)、帮助诊断和抑制 OSCC 细胞增殖的潜力。肿瘤相关抗原的模拟物能对癌细胞产生细胞毒性和免疫反应。转铁蛋白等基于生物标志物的方法有助于早期诊断 OSCC。一种改良的温带噬菌体引入了CRISPR-Cas3,以针对与OSCC相关的抗微生物细菌。这些研究成果突显了噬菌体诊断和治疗领域的不断发展,为非侵入性、有针对性地检测和治疗 OSCC 提供了一条新途径。然而,要验证噬菌体在创新性癌症治疗策略中的疗效,还需要进行广泛的临床研究。
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引用次数: 0
Human Virus-Like Proteins: Implications for Gene Therapy. 人类病毒样蛋白:对基因疗法的影响。
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-05-24 DOI: 10.2174/0115665232303436240515071754
Aya Al Othman, Anna Polyanskaya, Mikhail Durymanov

An analysis of mammalian genomes has revealed a significant number of DNA sequences with transposon or viral origin. Some of these elements encode functional proteins, repurposed during evolution to play significant physiological roles in certain tissues. Some human virus-like proteins, such as Peg10 and Arc/Arg3.1, structurally demonstrate significant similarity with Gag retroviral proteins, while others, like syncytins-1 and -2, resemble envelope viral proteins. In recent years, it has become clear that these proteins can be exploited for bioengineering 'humanized' capsid particles aimed at targeted mRNA delivery. Realizing this idea could provide efficient virus-like particles for gene therapy and address the problem of viral vector immunogenicity. This review provides an overview of the most-studied human proteins of viral or transposon origin and highlights their biological functions. Additionally, recent advances in exploiting these proteins for targeted mRNA delivery and prospects for their clinical application are discussed.

通过对哺乳动物基因组的分析,发现了大量源自转座子或病毒的 DNA 序列。其中一些元件编码功能蛋白,在进化过程中被重新利用,在某些组织中发挥重要的生理作用。一些人类病毒样蛋白,如 Peg10 和 Arc/Arg3.1,在结构上与 Gag 逆转录病毒蛋白非常相似,而另一些蛋白,如 syncytins-1 和-2,则类似于包膜病毒蛋白。近年来,这些蛋白显然可用于生物工程 "人性化 "的囊膜颗粒,以定向传递 mRNA。实现这一想法可为基因治疗提供高效的类病毒颗粒,并解决病毒载体的免疫原性问题。本综述概述了研究最多的病毒或转座子来源的人类蛋白质,并重点介绍了它们的生物学功能。此外,还讨论了利用这些蛋白质进行 mRNA 靶向传递的最新进展及其临床应用前景。
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引用次数: 0
SLC2A3 is a Potential Factor for Head and Neck Squamous Cancer Development through Tumor Microenvironment Alteration. SLC2A3 是通过肿瘤微环境改变导致头颈部鳞癌发展的潜在因素
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-05-21 DOI: 10.2174/0115665232291300240509104344
Wei Jiang, Sheng Xu, Ping Li

Introduction: Tumor immunity has garnered increasing attention in cancer treatment and progression. However, there is still a challenge in understanding the mechanisms of specific molecules affecting the clinical prognosis and tumor microenvironment (TME).

Method: Here, we applied the ESTIMATE algorithm to calculate the immune and stromal scores in 504 HNSC cases from TCGA. Patients were grouped according to the median value of the immune and stromal. Clinicopathological characteristics and differentially expressed genes (DEG) were analyzed. Subsequently, LASSO, COX regression, survival analysis, and clinicopathological characteristics were conducted. Subsequently, SLC2A3 was determined as a predictive factor that high expression of SLC2A3 at the mRNA and protein levels predicted a worse clinical prognosis. GSEA25099 was utilized for external validation of immune infiltration, while tissue PCR, IHC, and Western Blot were used to confirm the expression levels of SLC2A3.

Result: A series of immune-infiltration analyses showed that SLC2A3 expression was negatively correlated with CD8+ T cells, significantly affecting the survival prognosis of HNSC. In the GSEA analysis, the high expression of SLC2A3 was mainly enriched for immune-related biological processes. Meanwhile, high expression of SLC2A3 possessed higher TIDE scores and was also strongly positively correlated with a series of immune checkpoints affecting survival prognosis, thus causing greater susceptibility to immune escape.

Conclusion: Conclusively, SLC2A3 is a potential oncogene and factor of HNSC development, notably by an altered state of the immune microenvironment, immune-suppressive regulation, and immune escape.

简介肿瘤免疫在癌症治疗和进展中日益受到关注。然而,了解特定分子影响临床预后和肿瘤微环境(TME)的机制仍是一项挑战:在此,我们应用ESTIMATE算法计算了TCGA中504例HNSC病例的免疫和基质评分。根据免疫和基质评分的中位值对患者进行分组。对临床病理特征和差异表达基因(DEG)进行了分析。随后进行了LASSO、COX回归、生存分析和临床病理特征分析。随后,SLC2A3 被确定为一个预测因素,即 SLC2A3 在 mRNA 和蛋白水平的高表达预示着较差的临床预后。GSEA25099用于免疫浸润的外部验证,组织PCR、IHC和Western Blot用于确认SLC2A3的表达水平:一系列免疫浸润分析表明,SLC2A3的表达与CD8+ T细胞呈负相关,显著影响HNSC的生存预后。在GSEA分析中,SLC2A3的高表达主要富集于免疫相关的生物学过程。同时,SLC2A3的高表达具有更高的TIDE评分,还与一系列影响生存预后的免疫检查点呈强正相关,从而导致更易发生免疫逃逸:结论:SLC2A3是一种潜在的癌基因,也是HNSC发展的一个因素,主要通过改变免疫微环境状态、免疫抑制调节和免疫逃逸来实现。
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引用次数: 0
Lipid-Based Nanocarriers for Targeted Gene Delivery in Lung Cancer Therapy: Exploring a Novel Therapeutic Paradigm. 用于肺癌靶向基因递送治疗的脂质基纳米载体:探索新的治疗范例。
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-05-20 DOI: 10.2174/0115665232292768240503050508
Anahita Beigi, Seyed Morteza Naghib, Amir Matini, Maryam Tajabadi, M R Mozafari

Lung cancer is a significant cause of cancer-related death worldwide. It can be broadly categorised into small-cell lung cancer (SCLC) and Non-small cell lung cancer (NSCLC). Surgical intervention, radiation therapy, and the administration of chemotherapeutic medications are among the current treatment modalities. However, the application of chemotherapy may be limited in more advanced stages of metastasis due to the potential for adverse effects and a lack of cell selectivity. Although small-molecule anticancer treatments have demonstrated effectiveness, they still face several challenges. The challenges at hand in this context comprise insufficient solubility in water, limited bioavailability at specific sites, adverse effects, and the requirement for epidermal growth factor receptor inhibitors that are genetically tailored. Bio-macromolecular drugs, including small interfering RNA (siRNA) and messenger RNA (mRNA), are susceptible to degradation when exposed to the bodily fluids of humans, which can reduce stability and concentration. In this context, nanoscale delivery technologies are utilised. These agents offer encouraging prospects for the preservation and regulation of pharmaceutical substances, in addition to improving the solubility and stability of medications. Nanocarrier-based systems possess the notable advantage of facilitating accurate and sustained drug release, as opposed to traditional systemic methodologies. The primary focus of scientific investigation has been to augment the therapeutic efficacy of nanoparticles composed of lipids. Numerous nanoscale drug delivery techniques have been implemented to treat various respiratory ailments, such as lung cancer. These technologies have exhibited the potential to mitigate the limitations associated with conventional therapy. As an illustration, applying nanocarriers may enhance the solubility of small-molecule anticancer drugs and prevent the degradation of bio-macromolecular drugs. Furthermore, these devices can administer medications in a controlled and extended fashion, thereby augmenting the therapeutic intervention's effectiveness and reducing adverse reactions. However, despite these promising results, challenges remain that must be addressed. Multiple factors necessitate consideration when contemplating the application of nanoparticles in medical interventions. To begin with, the advancement of more efficient delivery methods is imperative. In addition, a comprehensive investigation into the potential toxicity of nanoparticles is required. Finally, additional research is needed to comprehend these treatments' enduring ramifications. Despite these challenges, the field of nanomedicine demonstrates considerable promise in enhancing the therapy of lung cancer and other respiratory diseases.

肺癌是全球癌症相关死亡的重要原因。肺癌大致可分为小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)。目前的治疗方法包括手术治疗、放射治疗和化疗药物。然而,由于化疗可能产生不良反应,而且缺乏细胞选择性,因此化疗在转移晚期的应用可能会受到限制。虽然小分子抗癌疗法已证明有效,但仍面临一些挑战。这方面的挑战包括在水中的溶解度不足、在特定部位的生物利用度有限、不良反应以及需要基因定制的表皮生长因子受体抑制剂。生物大分子药物,包括小干扰 RNA (siRNA) 和信使 RNA (mRNA),在暴露于人体体液时容易降解,从而降低稳定性和浓度。在这种情况下,纳米级给药技术应运而生。除了提高药物的溶解度和稳定性外,这些制剂还为药物的保存和调节提供了令人鼓舞的前景。与传统的系统方法相比,基于纳米载体的系统具有促进药物准确和持续释放的显著优势。科学研究的主要重点是提高由脂质组成的纳米颗粒的疗效。许多纳米级给药技术已用于治疗各种呼吸系统疾病,如肺癌。这些技术已显示出缓解与传统疗法相关的局限性的潜力。例如,应用纳米载体可以提高小分子抗癌药物的溶解度,防止生物大分子药物降解。此外,这些设备还能以受控和延长的方式给药,从而增强治疗干预的效果并减少不良反应。然而,尽管取得了这些令人鼓舞的成果,但仍存在必须应对的挑战。在考虑在医疗干预中应用纳米粒子时,必须考虑多种因素。首先,当务之急是改进更有效的给药方法。此外,还需要对纳米粒子的潜在毒性进行全面调查。最后,还需要开展更多研究,以了解这些治疗方法的持久影响。尽管存在这些挑战,但纳米医学领域在加强肺癌和其他呼吸系统疾病的治疗方面仍大有可为。
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引用次数: 0
Development of Cell and Gene Therapies for Clinical Use in the US and EU: Summary of Regulatory Guidelines 在美国和欧盟开发用于临床的细胞和基因疗法:监管指南摘要
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-04-27 DOI: 10.2174/0115665232306205240419091414
Anand Rotte
Recent decades have seen advancements in the management and treatment of difficult-- to-treat diseases such as cancer. A special class of therapeutics called cell and gene therapy has been introduced in the past 10 years. Cell and gene therapy products have strengthened the treatment options for life-threatening diseases with unmet clinical needs and also provided the possibility of a potential cure for the disease in some of the patients. Cell and gene therapy products are gaining recognition, and the interest in clinical development of cell and gene therapy products is increasing. Moreover, as the class of cell and gene therapy products is relatively new, there is a limited regulatory experience in the development, and the developers of the cell and gene therapy products can often be puzzled with an array of questions on regulations. The current review intends to provide a basic understanding of regulatory guidelines from the FDA and EMA that are applicable to cell and gene therapy products. Essentials such as which office is responsible for the evaluation of applications, which regulatory class/pathway is appropriate for development, and what are the quality, nonclinical and clinical studies that are needed to support the application are discussed in the article. In addition, a summary of regulatory designations and the post-approval requirements, such as Risk Evaluation and Mitigation Strategies (REMS) and long-term follow- up, is included in the article. Developers (referred to as ‘sponsors’ in this article) of cell and gene therapies can use the respective guidance documents and other specific review articles cited in this review for detailed information on the topics.
近几十年来,癌症等难治疾病的管理和治疗取得了长足进步。在过去 10 年中,出现了一类特殊的疗法,即细胞和基因疗法。细胞和基因治疗产品加强了对临床需求未得到满足的危及生命的疾病的治疗选择,也为部分患者提供了治愈疾病的可能性。细胞和基因治疗产品正得到越来越多的认可,人们对细胞和基因治疗产品临床开发的兴趣也在不断增加。此外,由于细胞和基因治疗产品是相对较新的一类产品,在开发过程中的监管经验有限,细胞和基因治疗产品的开发者往往会对监管方面的一系列问题感到困惑。本综述旨在让人们基本了解适用于细胞和基因治疗产品的 FDA 和 EMA 监管指南。文章讨论了一些基本要素,如哪个部门负责评估申请,哪个监管类别/途径适合开发,支持申请所需的质量、非临床和临床研究有哪些。此外,文章还概述了监管指定和批准后的要求,如风险评估与缓解策略(REMS)和长期随访。细胞和基因疗法的开发者(本文中称为 "申办者")可参阅本综述中引用的相关指导文件和其他特定综述文章,了解有关主题的详细信息。
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引用次数: 0
Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance in Cancer Cells 非编码 RNA 对癌症细胞放疗敏感性和耐受性的作用
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-04-27 DOI: 10.2174/0115665232301727240422092311
Fatemeh Jalali-Zefrei, Seyed Mehdi Mousavi, Kourosh Delpasand, Mohammad Shourmij, Soghra Farzipour
: Radiotherapy (RT) is an integral part of treatment management in cancer patients. However, one of the limitations of this treatment method is the resistance of cancer cells to radiotherapy. These restrictions necessitate the introduction of modalities for the radiosensitization of cancer cells. It has been shown that Noncoding RNAs (ncRNAs), along with modifiers, can act as radiosensitivity and radioresistant regulators in a variety of cancers by affecting double strand break (DSB), wnt signaling, glycolysis, irradiation induced apoptosis, ferroptosis and cell autophagy. This review will provide an overview of the latest research on the roles and regulatory mechanisms of ncRNA after RT in in vitro and preclinical research.
:放射治疗(RT)是癌症患者治疗过程中不可或缺的一部分。然而,这种治疗方法的局限性之一是癌细胞对放疗的抗药性。由于这些限制,有必要引入对癌细胞进行放射增敏的方法。研究表明,非编码 RNA(ncRNA)和修饰因子可通过影响双链断裂(DSB)、wnt 信号转导、糖酵解、辐照诱导的细胞凋亡、铁凋亡和细胞自噬,在多种癌症中充当放射敏感性和抗放射调节因子。本综述将概述体外和临床前研究中有关 RT 后 ncRNA 作用和调控机制的最新研究。
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引用次数: 0
Evolution of Prime Editing Systems: Move Forward to the Treatment of Hereditary Diseases 基因编辑系统的演变:向治疗遗传性疾病迈进
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-04-16 DOI: 10.2174/0115665232295117240405070809
Olga V. Volodina, Anastasia R. Fabrichnikova, Arina A. Anuchina, Olesya S. Mishina, Alexander V. Lavrov, Svetlana A. Smirnikhina
: The development of gene therapy using genome editing tools recently became relevant. With the invention of programmable nucleases, it became possible to treat hereditary diseases due to introducing targeted double strand break in the genome followed by homology directed repair (HDR) or non-homologous end-joining (NHEJ) reparation. CRISPR-Cas9 is more efficient and easier to use in comparison with other programmable nucleases. To improve the efficiency and safety of this gene editing tool, various modifications CRISPR-Cas9 basis were created in recent years, such as prime editing – in this system, Cas9 nickase is fused with reverse transcriptase and guide RNA, which contains a desired correction. Prime editing demonstrates equal or higher correction efficiency as HDR-mediated editing and much less off-target effect due to inducing nick. There are several studies in which prime editing is used to correct mutations in which researchers reported little or no evidence of off-target effects. The system can also be used to functionally characterize disease variants. However, prime editing still has several limitations that could be further improved. The effectiveness of the method is not yet high enough to apply it in clinical trials. Delivery of prime editors is also a big challenge due to their size. In the present article, we observe the development of the platform, and discuss the candidate proteins for efficiency enhancing, main delivery methods and current applications of prime editing.
:利用基因组编辑工具进行基因治疗的发展近来变得十分重要。随着可编程核酸酶的发明,通过在基因组中引入靶向双链断裂,然后进行同源定向修复(HDR)或非同源末端连接(NHEJ)修复,治疗遗传性疾病成为可能。与其他可编程核酸酶相比,CRISPR-Cas9 更高效、更易用。为了提高这种基因编辑工具的效率和安全性,近年来出现了各种基于CRISPR-Cas9的改良方法,如质粒编辑--在这种系统中,Cas9缺口酶与反转录酶和含有所需校正的引导RNA融合。质粒编辑与 HDR 介导的编辑具有相同或更高的校正效率,而且由于诱导缺口而产生的脱靶效应要小得多。有几项研究使用质粒编辑来校正突变,研究人员报告称几乎没有证据表明存在脱靶效应。该系统还可用于确定疾病变异的功能特征。不过,质粒编辑仍有一些局限性,有待进一步改进。该方法的有效性还不足以将其应用于临床试验。由于质粒编辑器体积庞大,其输送也是一个巨大的挑战。在本文中,我们观察了该平台的发展,并讨论了提高效率的候选蛋白质、主要的传递方法和当前的素编辑应用。
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引用次数: 0
Efficacy and Safety of Pembrolizumab Monotherapy or Combined Therapy in Patients with Metastatic Triple-negative Breast Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials Pembrolizumab单药或联合疗法对转移性三阴性乳腺癌患者的疗效和安全性:随机对照试验的系统回顾和元分析
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-03-12 DOI: 10.2174/0115665232283880240301035621
Mahmood Araghi, Farshad Gharebakhshi, Fatemeh Faramarzi, Alireza mafi, Tahoora Mousavi, Mina Alimohammadi, Hussein Soleimantabar
Background: Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advantages and disadvantages of pembrolizumab, and early data from numerous trials suggests that patients with mTNBC have had remarkable outcomes. This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination therapies for mTNBC. Methods: To identify eligible RCTs, a thorough literature search was carried out using electronic databases. CMA software was utilized to perform heterogeneity tests using fixed and random-effects models. Results: According to our pooled data, the median Progression-free Survival (PFS) was 2.66 months, and the median overall survival (OS) was 12.26 months. Furthermore, by comparing efficacy indicators between PD-L1–positive and PD-L1–negative groups, a correlation was found between the overexpression of PD-L1 with OS, PFS, and ORR. Patients with PD-L1-positive tumors had a higher response rate, with an ORR of 21.1%, compared to the patients with PD-L1-negative tumors. The ORR for first-line immunotherapy was higher than that of ≥second-line immunotherapy. In addition, pembrolizumab plus combination treatment resulted in a pooled incidence of immune-related adverse events of 22.7%. Conclusion: A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive.
背景:转移性三阴性乳腺癌(mTNBC转移性三阴性乳腺癌(mTNBC)是侵袭性最强的乳腺癌,转移和复发的风险更大。已有研究对pembrolizumab的优缺点进行了深入分析,大量试验的早期数据表明,mTNBC患者的疗效显著。本荟萃分析比较了众多相关研究的数据,以评估pembrolizumab单药或联合疗法治疗mTNBC的安全性和有效性。研究方法为了确定符合条件的 RCT,我们使用电子数据库进行了全面的文献检索。利用 CMA 软件使用固定效应和随机效应模型进行异质性检验。结果根据我们的汇总数据,中位无进展生存期(PFS)为 2.66 个月,中位总生存期(OS)为 12.26 个月。此外,通过比较 PD-L1 阳性组和 PD-L1 阴性组的疗效指标,我们发现 PD-L1 的过度表达与 OS、PFS 和 ORR 之间存在相关性。与PD-L1阴性肿瘤患者相比,PD-L1阳性肿瘤患者的反应率更高,ORR为21.1%。一线免疫疗法的ORR高于≥二线免疫疗法。此外,pembrolizumab+联合治疗导致的免疫相关不良事件发生率为22.7%。结论mTNBC患者对pembrolizumab单药治疗有一定的反应。此外,PD-L1阳性、非肝/肺转移、联合治疗和一线免疫治疗可能预示着Pembrolizumab治疗的更好结果。Pembrolizumab与化疗联合使用可能对PD-L1阳性肿瘤患者更有利。
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引用次数: 0
The Functions and Application Prospects of Hepatocyte Growth Factor in Reproduction 肝细胞生长因子在生殖领域的功能和应用前景
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-02-28 DOI: 10.2174/0115665232291010240221104445
Xin Mi, Caiyi Chen, Chen Feng, Yingying Qin, Zi-Jiang Chen, Yajuan Yang, Shidou Zhao
: Hepatocyte growth factor (HGF) is expressed in multiple systems and mediates a variety of biological activities, such as mitosis, motility, and morphogenesis. A growing number of studies have revealed the expression patterns and functions of HGF in ovarian and testicular physiology from the prenatal to the adult stage. HGF regulates folliculogenesis and steroidogenesis by modulating the functions of theca cells and granulosa cells in the ovary. It also mediates somatic cell proliferation and steroidogenesis, thereby affecting spermatogenesis in males. In addition to its physiological effects on the reproductive system, HGF has shown advantages in preclinical studies over recent years for the treatment of male and female infertility, particularly in women with premature ovarian insufficiency. This review aims to summarize the pleiotropic functions of HGF in the reproductive system and to provide prospects for its clinical application.
:肝细胞生长因子(HGF)在多个系统中表达,并介导多种生物活动,如有丝分裂、运动和形态发生。越来越多的研究揭示了肝细胞生长因子在卵巢和睾丸从出生前到成年阶段的生理过程中的表达模式和功能。HGF 通过调节卵巢中卵丘细胞和颗粒细胞的功能来调节卵泡生成和类固醇生成。它还能介导体细胞增殖和类固醇生成,从而影响男性的精子发生。除了对生殖系统的生理作用外,近年来,HGF 在治疗男性和女性不孕症,尤其是卵巢早衰妇女不孕症的临床前研究中也显示出其优势。本综述旨在总结 HGF 在生殖系统中的多种功能,并展望其临床应用前景。
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引用次数: 0
Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats 牛乳铁蛋白处理对大鼠伤口愈合过程中铁稳态和多器官功能障碍基因表达变化的影响
IF 3.6 4区 医学 Q2 GENETICS & HEREDITY Pub Date : 2024-02-22 DOI: 10.2174/0115665232279426240217174738
Ahmet Sarper Bozkurt, Şenay Görücü Yılmaz
Background:: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. Objectives:: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. Materials and Methods:: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. Results:: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P < 0.05) except for the SLC40A1 gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). Conclusion:: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.
背景损伤会破坏体内平衡,导致器官衰竭。LF 可介导铁依赖性和铁依赖性机制,LF 在调节铁平衡方面的作用对新陈代谢至关重要。研究目的本研究评估了 bLf 在皮肤修复过程中的器官效应和基因表达变化。材料与方法以饲喂高脂饮食(HFD)的雄性 Sprague Dawley 大鼠(180-250 g)(n = 48)为对象,建立切除性全厚度皮肤缺损(FTSD)伤口模型,并对 PHGPx、SLC7A11 和 SLC40A1 基因及铁代谢进行评估。动物被随机分为 6 组:1- 对照组,2- bLf(200 毫克/千克/天,口服)组,3- FTSD(直径 12 毫米,背侧)组,4- HFD + bLf 组,5- HFD + FTSD 组,6- HFD + FTSD + bLf 组。组织学上,肝脏、肾脏和肠道组织的普鲁士蓝染色显示了铁的积累。基因表达分析通过 qPCR 进行。结果组织学上,肝脏、肾脏和肠道组织的普鲁士蓝染色显示了铁的积累。肾脏中检测到普鲁士蓝反应。除 SLC40A1 基因(P> 0.05)外,肝肾组织中 PHPGx 和 SLC7A11 基因的表达均有统计学意义(P< 0.05)。在对大鼠肠道组织的分析中,这三个基因的表达变化无统计学意义(P = 0.057)。结论在由伤口形成引发的器官级铁变态损伤机制中。BLf 可控制三个基因的表达,并管理这三个组织中的铁沉积。此外,它还抑制了铁的增加,而铁的增加会促使细胞发生铁变态反应和炎症引起的贫血,从而消除组织中的铁沉积。
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Current gene therapy
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