The interaction between macrophages and cardiomyocytes plays an important role not only in maintaining cardiac homeostasis, but also in the development of many cardiovascular diseases (CVDs), such as myocardial infarction (MI) and heart failure (HF). In addition to supporting cardiomyocytes, macrophages and cardiomyocytes have a close and complex relationship. By studying their cross-talk, we can better understand novel mechanisms and target pathogenic mechanisms, and improve the treatment of CVDs. We review macrophage-cardiomyocyte communication through connexin 43 (Cx43)-containing gap junctions (GJs) directly, secreted protein factors indirectly, and discuss the implications of these interactions in cardiac homeostasis and the development of various CVDs, including MI, HF, arrhythmia, cardiac fibrosis and myocarditis. In this section, we review various drugs that work by modulating cytokines or other proteins to reduce inflammation in CVDs. The clinical findings from targeting inflammation in CVDs are also discussed. Additionally, we examine the challenges and opportunities for improving our understanding of macrophage-cardiomyocyte coupling as it relates to pathophysiological disease processes, extending our research scope, and helping identify new molecular targets and improve the effectiveness of existing therapies.
{"title":"The effect of macrophage-cardiomyocyte interactions on cardiovascular diseases and development of potential drugs.","authors":"Shoupeng Cao, Shengjie Wang, Huishan Luo, Jianjun Guo, Lina Xuan, Lihua Sun","doi":"10.1007/s11033-024-09944-1","DOIUrl":"https://doi.org/10.1007/s11033-024-09944-1","url":null,"abstract":"<p><p>The interaction between macrophages and cardiomyocytes plays an important role not only in maintaining cardiac homeostasis, but also in the development of many cardiovascular diseases (CVDs), such as myocardial infarction (MI) and heart failure (HF). In addition to supporting cardiomyocytes, macrophages and cardiomyocytes have a close and complex relationship. By studying their cross-talk, we can better understand novel mechanisms and target pathogenic mechanisms, and improve the treatment of CVDs. We review macrophage-cardiomyocyte communication through connexin 43 (Cx43)-containing gap junctions (GJs) directly, secreted protein factors indirectly, and discuss the implications of these interactions in cardiac homeostasis and the development of various CVDs, including MI, HF, arrhythmia, cardiac fibrosis and myocarditis. In this section, we review various drugs that work by modulating cytokines or other proteins to reduce inflammation in CVDs. The clinical findings from targeting inflammation in CVDs are also discussed. Additionally, we examine the challenges and opportunities for improving our understanding of macrophage-cardiomyocyte coupling as it relates to pathophysiological disease processes, extending our research scope, and helping identify new molecular targets and improve the effectiveness of existing therapies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1007/s11033-024-10016-7
P Zeebul Trinita Shannan, Susan G Suganya, M Ramesh, E Angel Jemima
Background: Most anticancer drugs possess the capacity to control precise molecular processes and gene-regulated protein expressions, which could enhance the efficacy of cancer treatments. Hirudinaria manillensis is prevalent in South Asia and has been employed for several decades in medical conditions based on its curative benefits.
Methods and results: The present study aimed to explore the molecular regulation of the target EGFR gene, and the protein expression of EGFR on the HeLa cell line. To achieve our aim, quantitative real-time PCR and immunocytochemistry assays were conducted. Interestingly, qRT-PCR results confirmed the downregulation of the EGFR gene on the HeLa cells in comparison with the β- actin internal control gene. Furthermore, immunocytochemistry assay results confirmed the decreasing level of EGFR gene expression in the HeLa cells.
Conclusion: Therefore, Hirudinaria manillensis could be a promising anticancer candidate for cervical cancer treatment.
背景:大多数抗癌药物都具有精确控制分子过程和基因调控蛋白表达的能力,这可以提高癌症治疗的疗效。Hirudinaria manillensis盛产于南亚,几十年来一直被用于治疗各种疾病:本研究旨在探讨目标表皮生长因子受体基因的分子调控以及表皮生长因子受体蛋白在 HeLa 细胞系中的表达。为了达到这一目的,我们进行了实时定量 PCR 和免疫细胞化学分析。有趣的是,与β-肌动蛋白内对照基因相比,qRT-PCR 结果证实了表皮生长因子受体基因在 HeLa 细胞上的下调。此外,免疫细胞化学分析结果也证实了 HeLa 细胞中表皮生长因子受体基因表达水平的下降:因此,马氏葫芦巴可能是治疗宫颈癌的一种有前途的抗癌候选药物。
{"title":"Effect control of novel Hirudinaria manillensis extract on the molecular regulation of EGFR gene and its protein expression in HeLa cells.","authors":"P Zeebul Trinita Shannan, Susan G Suganya, M Ramesh, E Angel Jemima","doi":"10.1007/s11033-024-10016-7","DOIUrl":"https://doi.org/10.1007/s11033-024-10016-7","url":null,"abstract":"<p><strong>Background: </strong>Most anticancer drugs possess the capacity to control precise molecular processes and gene-regulated protein expressions, which could enhance the efficacy of cancer treatments. Hirudinaria manillensis is prevalent in South Asia and has been employed for several decades in medical conditions based on its curative benefits.</p><p><strong>Methods and results: </strong>The present study aimed to explore the molecular regulation of the target EGFR gene, and the protein expression of EGFR on the HeLa cell line. To achieve our aim, quantitative real-time PCR and immunocytochemistry assays were conducted. Interestingly, qRT-PCR results confirmed the downregulation of the EGFR gene on the HeLa cells in comparison with the β- actin internal control gene. Furthermore, immunocytochemistry assay results confirmed the decreasing level of EGFR gene expression in the HeLa cells.</p><p><strong>Conclusion: </strong>Therefore, Hirudinaria manillensis could be a promising anticancer candidate for cervical cancer treatment.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1007/s11033-024-09937-0
Praveen Belagal
Background: Earlier work in this laboratory revealed that fitA was same as pheS as a recombinant clone, pSRJ5R1 harboring pheS+ gene complemented transcription-defective fitA76 Ts (temperature sensitive) mutant. However, this clone lacked the native promoter (NP) of pheST operon. A putative - 10 promoter like element was suggested to act as promoter in this clone. This work investigated the veracity of this putative promoter as well as its downstream regulatory region towards driving the pheS expression.
Methods: Plasmid clones with promoter-mutations or -deletions were constructed by PCR-based cloning and their ability to complement fitA76 Ts mutant strains was checked. Chromosomal mutations were transferred into various genetic backgrounds via P1-transductions. Relative viability assays were performed to check the extent of complementation.
Results: Clones harboring point mutations (PM-pheS) or deletion (PD1-pheS) of - 10 region of the putative promoter did not abolish complementation of the fitA76 Ts phenotype. Subsequently, a novel alternate promoter (AP) was discovered by downstream deletion clone (PD2-pheS) which failed to complement. Keeping PD1-pheS intact but mutating initiation codon of pheS (ATG→TTG) failed to complement. Complementation ability of novel alternate promoter is poor in HfrC strain background unlike native promoter which complements well independent of strain background.
Conclusion: A novel alternate-promoter of pheST operon was identified by mutational/deletional analyses and earlier reported putative - 10 promoter was shown to be dispensable. Alternate promoter is relA dependent.
{"title":"Identification of a novel alternate promoter element in the pheST operon of Escherichia coli.","authors":"Praveen Belagal","doi":"10.1007/s11033-024-09937-0","DOIUrl":"https://doi.org/10.1007/s11033-024-09937-0","url":null,"abstract":"<p><strong>Background: </strong>Earlier work in this laboratory revealed that fitA was same as pheS as a recombinant clone, pSRJ5R1 harboring pheS<sup>+</sup> gene complemented transcription-defective fitA76 Ts (temperature sensitive) mutant. However, this clone lacked the native promoter (NP) of pheST operon. A putative - 10 promoter like element was suggested to act as promoter in this clone. This work investigated the veracity of this putative promoter as well as its downstream regulatory region towards driving the pheS expression.</p><p><strong>Methods: </strong>Plasmid clones with promoter-mutations or -deletions were constructed by PCR-based cloning and their ability to complement fitA76 Ts mutant strains was checked. Chromosomal mutations were transferred into various genetic backgrounds via P1-transductions. Relative viability assays were performed to check the extent of complementation.</p><p><strong>Results: </strong>Clones harboring point mutations (PM-pheS) or deletion (PD1-pheS) of - 10 region of the putative promoter did not abolish complementation of the fitA76 Ts phenotype. Subsequently, a novel alternate promoter (AP) was discovered by downstream deletion clone (PD2-pheS) which failed to complement. Keeping PD1-pheS intact but mutating initiation codon of pheS (ATG→TTG) failed to complement. Complementation ability of novel alternate promoter is poor in HfrC strain background unlike native promoter which complements well independent of strain background.</p><p><strong>Conclusion: </strong>A novel alternate-promoter of pheST operon was identified by mutational/deletional analyses and earlier reported putative - 10 promoter was shown to be dispensable. Alternate promoter is relA dependent.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1007/s11033-024-09999-0
Seyede Mehrana Salehi-Reyhani, Mostafa Saadat
Background: It is well known that telomerase activity is suppressed in normal human tissues and reactivated in tumors, suggesting that the human telomerase reverse transcriptase (hTERT, MIM: 187270) gene may be involved in carcinogenesis. A polymorphic tandem repeat minisatellite located downstream of exon 16 of hTERT and upstream in the putative promoter region of an antisense hTERT transcript, termed MNS16A, results in a functional polymorphism. Because the association between the MNS16A genetic polymorphism and breast cancer (BC) risk remains an open question, the present case-control study was conducted in Shiraz (Fars Province, Southern Iran).
Methods: A total of 711 samples were collected, including 362 BC patients and 349 healthy individuals. Genotyping was performed by polymerase chain reaction method. Alleles were determined by classifying DNA amplicons of less than and greater than 300 bp as short (S) and long (L) alleles, respectively.
Results: Different inheritance models (codominant, dominant, recessive, overdominant genotype models and the allele model) were used to evaluate the association between the MNS16A polymorphism and the risk of BC. No significant association was observed in any of the analyses. It should be noted that the statistical power of the comparisons was low.
Conclusion: The present study did not support the association between hTERT MNS16A polymorphism and breast cancer risk. Similar studies in other populations with larger sample sizes are needed to determine the association between the hTERT MNS16A polymorphism and susceptibility to breast cancer.
背景:众所周知,端粒酶活性在正常人体组织中受到抑制,而在肿瘤中被重新激活,这表明人类端粒酶逆转录酶(hTERT,MIM: 187270)基因可能与致癌有关。位于 hTERT 第 16 号外显子下游和反义 hTERT 转录本推测启动子区上游的多态串联重复小卫星(称为 MNS16A)导致了一种功能性多态性。由于 MNS16A 基因多态性与乳腺癌(BC)风险之间的关系仍是一个未决问题,因此本病例对照研究在设拉子(伊朗南部法尔斯省)进行:方法:共收集了 711 份样本,包括 362 名 BC 患者和 349 名健康人。采用聚合酶链反应法进行基因分型。通过将小于和大于 300 bp 的 DNA 扩增子分别划分为短等位基因(S)和长等位基因(L)来确定等位基因:结果:采用了不同的遗传模型(共显性、显性、隐性、过显性基因型模型和等位基因模型)来评估 MNS16A 多态性与 BC 风险之间的关联。在所有分析中均未观察到明显的关联。值得注意的是,比较的统计能力较低:本研究不支持 hTERT MNS16A 多态性与乳腺癌风险之间的关联。要确定 hTERT MNS16A 多态性与乳腺癌易感性之间的关系,还需要在其他人群中进行样本量更大的类似研究。
{"title":"Association between human telomerase reverse transcriptase (hTERT) MNS16A polymorphism and risk of breast cancer.","authors":"Seyede Mehrana Salehi-Reyhani, Mostafa Saadat","doi":"10.1007/s11033-024-09999-0","DOIUrl":"https://doi.org/10.1007/s11033-024-09999-0","url":null,"abstract":"<p><strong>Background: </strong>It is well known that telomerase activity is suppressed in normal human tissues and reactivated in tumors, suggesting that the human telomerase reverse transcriptase (hTERT, MIM: 187270) gene may be involved in carcinogenesis. A polymorphic tandem repeat minisatellite located downstream of exon 16 of hTERT and upstream in the putative promoter region of an antisense hTERT transcript, termed MNS16A, results in a functional polymorphism. Because the association between the MNS16A genetic polymorphism and breast cancer (BC) risk remains an open question, the present case-control study was conducted in Shiraz (Fars Province, Southern Iran).</p><p><strong>Methods: </strong>A total of 711 samples were collected, including 362 BC patients and 349 healthy individuals. Genotyping was performed by polymerase chain reaction method. Alleles were determined by classifying DNA amplicons of less than and greater than 300 bp as short (S) and long (L) alleles, respectively.</p><p><strong>Results: </strong>Different inheritance models (codominant, dominant, recessive, overdominant genotype models and the allele model) were used to evaluate the association between the MNS16A polymorphism and the risk of BC. No significant association was observed in any of the analyses. It should be noted that the statistical power of the comparisons was low.</p><p><strong>Conclusion: </strong>The present study did not support the association between hTERT MNS16A polymorphism and breast cancer risk. Similar studies in other populations with larger sample sizes are needed to determine the association between the hTERT MNS16A polymorphism and susceptibility to breast cancer.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50 mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels.
{"title":"Down regulation of the c-Fos/MAP kinase signaling pathway during learning memory processes coincides with low GnRH levels in aluminum chloride-induced Alzheimer's male rats.","authors":"Reza Lotfizadeh, Manizheh Karami, Mohammadreza Jalali-Nadoushan","doi":"10.1007/s11033-024-09987-4","DOIUrl":"https://doi.org/10.1007/s11033-024-09987-4","url":null,"abstract":"<p><p>Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50 mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1007/s11033-024-10009-6
Megumi Kono, Kyoko Yamasaki, Morihiko Nakamura
Background: Monoclonal nonspecific suppressor factor β (MNSFβ), a ubiquitously expressed member of the ubiquitin-like protein family, is associated with diverse cell regulatory functions. It has been implicated in glycolysis regulation and cell proliferation enhancement in the macrophage-like cell line Raw264.7. This study aims to show that HIF-1α regulates MNSFβ-mediated metabolic reprogramming.
Methods and results: In Raw264.7 cells, MNSFβ siRNA increased the oxygen consumption rate and reactive oxygen species (ROS) production but decreased ATP levels. Cells with MNSFβ knockdown showed a markedly increased ATP reduction rate upon the addition of oligomycin, a mitochondrial ATP synthase inhibitor. In addition, MNSFβ siRNA decreased the expression levels of mRNA and protein of HIF-1α-a regulator of glucose metabolism. Evaluation of the effect of MNSFβ on glucose metabolism in murine peritoneal macrophages revealed no changes in lactate production, glucose consumption, or ROS production.
Conclusion: MNSFβ affects both glycolysis and mitochondrial metabolism, suggesting HIF-1α involvement in the MNSFβ-regulated glucose metabolism in Raw264.7 cells.
背景:单克隆非特异性抑制因子β(MNSFβ)是泛素样蛋白家族中的一个泛素表达成员,与多种细胞调控功能有关。它与巨噬细胞样细胞系 Raw264.7 的糖酵解调节和细胞增殖增强有关。本研究旨在证明 HIF-1α 可调控 MNSFβ 介导的代谢重编程:在 Raw264.7 细胞中,MNSFβ siRNA 增加了氧消耗率和活性氧(ROS)的产生,但降低了 ATP 水平。在加入线粒体 ATP 合成酶抑制剂寡霉素后,MNSFβ siRNA 被敲除的细胞显示 ATP 减少率明显增加。此外,MNSFβ siRNA 还降低了葡萄糖代谢调节因子 HIF-1α 的 mRNA 和蛋白表达水平。通过评估 MNSFβ 对小鼠腹腔巨噬细胞葡萄糖代谢的影响,发现乳酸生成、葡萄糖消耗和 ROS 生成均无变化:结论:MNSFβ同时影响糖酵解和线粒体代谢,表明HIF-1α参与了MNSFβ调节Raw264.7细胞的糖代谢。
{"title":"Investigating the regulatory mechanism of glucose metabolism by ubiquitin-like protein MNSFβ.","authors":"Megumi Kono, Kyoko Yamasaki, Morihiko Nakamura","doi":"10.1007/s11033-024-10009-6","DOIUrl":"https://doi.org/10.1007/s11033-024-10009-6","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal nonspecific suppressor factor β (MNSFβ), a ubiquitously expressed member of the ubiquitin-like protein family, is associated with diverse cell regulatory functions. It has been implicated in glycolysis regulation and cell proliferation enhancement in the macrophage-like cell line Raw264.7. This study aims to show that HIF-1α regulates MNSFβ-mediated metabolic reprogramming.</p><p><strong>Methods and results: </strong>In Raw264.7 cells, MNSFβ siRNA increased the oxygen consumption rate and reactive oxygen species (ROS) production but decreased ATP levels. Cells with MNSFβ knockdown showed a markedly increased ATP reduction rate upon the addition of oligomycin, a mitochondrial ATP synthase inhibitor. In addition, MNSFβ siRNA decreased the expression levels of mRNA and protein of HIF-1α-a regulator of glucose metabolism. Evaluation of the effect of MNSFβ on glucose metabolism in murine peritoneal macrophages revealed no changes in lactate production, glucose consumption, or ROS production.</p><p><strong>Conclusion: </strong>MNSFβ affects both glycolysis and mitochondrial metabolism, suggesting HIF-1α involvement in the MNSFβ-regulated glucose metabolism in Raw264.7 cells.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1007/s11033-024-09931-6
Swati Agrawal, Anna Podber, Megan Gillespie, Nick Dietz, Laura A Hansen, Kalyana C Nandipati
Background: Obesity is a risk factor for esophageal adenocarcinoma (EAC). It was reported that obesity -associated inflammation correlates with insulin resistance and increased risk of EAC. The objective of the study is to investigate the role of obesity associated inflammatory mediators in the development of EAC.
Methods: We included 23 obese and nonobese patients with EAC or with or without Barrett's esophagus (BE) after IRB approval. We collected 23 normal, 10 BE, and 19 EAC tissue samples from endoscopy or esophagectomy. The samples were analyzed for the expression levels of pro-apoptotic and anti-apoptotic factors, PKC-δ, cIAP2, FLIP, IGF-1, Akt, NF-kB and Ki67 by immunofluorescence and RT-PCR. We compared the expression levels between normal, BE, and EAC tissue using Students' t-test between two groups.
Results: Our results showed decreased gene and protein expression of pro-apoptotic factors (bad, bak and bax) and increased expression of anti-apoptotic factors (bcl-2, Bcl-xL) in BE and EAC compared to normal tissues. There was increased gene and protein expression of PKC-δ, cIAP2, FLIP, NF-kB, IGF-1, Akt, and Ki67 in BE and EAC samples compared to normal esophagus. Further, an increased folds changes in mRNA expression of proapoptotic factors, antiapoptotic factors, PKC-δ, IGF-1, Akt, and Ki-67 was associated with obesity.
Conclusion: Patients with EAC had increased expression of cIAP2 and FLIP, and PKC-δ which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma.
{"title":"Regulation of pro-apoptotic and anti-apoptotic factors in obesity-related esophageal adenocarcinoma.","authors":"Swati Agrawal, Anna Podber, Megan Gillespie, Nick Dietz, Laura A Hansen, Kalyana C Nandipati","doi":"10.1007/s11033-024-09931-6","DOIUrl":"https://doi.org/10.1007/s11033-024-09931-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a risk factor for esophageal adenocarcinoma (EAC). It was reported that obesity -associated inflammation correlates with insulin resistance and increased risk of EAC. The objective of the study is to investigate the role of obesity associated inflammatory mediators in the development of EAC.</p><p><strong>Methods: </strong>We included 23 obese and nonobese patients with EAC or with or without Barrett's esophagus (BE) after IRB approval. We collected 23 normal, 10 BE, and 19 EAC tissue samples from endoscopy or esophagectomy. The samples were analyzed for the expression levels of pro-apoptotic and anti-apoptotic factors, PKC-δ, cIAP2, FLIP, IGF-1, Akt, NF-kB and Ki67 by immunofluorescence and RT-PCR. We compared the expression levels between normal, BE, and EAC tissue using Students' t-test between two groups.</p><p><strong>Results: </strong>Our results showed decreased gene and protein expression of pro-apoptotic factors (bad, bak and bax) and increased expression of anti-apoptotic factors (bcl-2, Bcl-xL) in BE and EAC compared to normal tissues. There was increased gene and protein expression of PKC-δ, cIAP2, FLIP, NF-kB, IGF-1, Akt, and Ki67 in BE and EAC samples compared to normal esophagus. Further, an increased folds changes in mRNA expression of proapoptotic factors, antiapoptotic factors, PKC-δ, IGF-1, Akt, and Ki-67 was associated with obesity.</p><p><strong>Conclusion: </strong>Patients with EAC had increased expression of cIAP2 and FLIP, and PKC-δ which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1007/s11033-024-09978-5
Devika Tripathi, Tanya Gupta, Prashant Pandey
Radiotherapy is a cornerstone in the treatment of solid tumors, with extensive Phase III trials confirming its effectiveness. As advancements in treatment technologies and our understanding of tumor resistance mechanisms continue, the role of radiation oncology is set to become even more pivotal. Addressing the global challenge of lethal cancers demands innovative strategies, particularly in minimizing the side effects associated with traditional chemotherapy and ionizing radiation (IR). Recently, there has been growing interest in natural compounds for radioprotection, aiming to prevent tumor development and metastasis. Piperine, a compound found in black and long pepper, has emerged as a promising chemopreventive agent that works effectively without harming normal cells. Mechanistically, piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to IR. Combining piperine with radiotherapy offers a compelling approach, boosting treatment efficacy while protecting healthy tissues from radiation damage. Piperine's versatile role goes beyond radiosensitization to include radioprotection by inhibiting NF-κB activation, reducing autophagy, and promoting apoptosis in cancer cells. This dual action makes it a promising candidate for personalized cancer care. As research advances, the therapeutic potential of piperine may drive new frontiers in cancer treatment strategies.
放疗是治疗实体瘤的基石,大量的 III 期试验证实了它的有效性。随着治疗技术的不断进步和我们对肿瘤抗药性机制的不断了解,放射肿瘤学的作用将变得更加举足轻重。应对致命癌症这一全球性挑战需要创新战略,尤其是在最大限度地减少传统化疗和电离辐射(IR)的副作用方面。最近,人们对天然化合物的辐射防护作用越来越感兴趣,其目的是防止肿瘤的发展和转移。胡椒碱是一种存在于黑胡椒和长辣椒中的化合物,它是一种很有前途的化学预防剂,能在不伤害正常细胞的情况下有效发挥作用。从机理上讲,胡椒碱能调节关键信号通路,抑制癌细胞迁移和侵袭,并提高对红外线的敏感性。将胡椒碱与放疗相结合是一种令人信服的方法,既能提高疗效,又能保护健康组织免受辐射损伤。胡椒碱的多功能作用不仅限于放射增敏,还包括通过抑制 NF-κB 激活、减少自噬和促进癌细胞凋亡来实现放射保护。这种双重作用使它有望成为个性化癌症治疗的候选药物。随着研究的深入,胡椒碱的治疗潜力可能会推动癌症治疗策略的新发展。
{"title":"Exploring Piperine: Unleashing the multifaceted potential of a phytochemical in cancer therapy.","authors":"Devika Tripathi, Tanya Gupta, Prashant Pandey","doi":"10.1007/s11033-024-09978-5","DOIUrl":"https://doi.org/10.1007/s11033-024-09978-5","url":null,"abstract":"<p><p>Radiotherapy is a cornerstone in the treatment of solid tumors, with extensive Phase III trials confirming its effectiveness. As advancements in treatment technologies and our understanding of tumor resistance mechanisms continue, the role of radiation oncology is set to become even more pivotal. Addressing the global challenge of lethal cancers demands innovative strategies, particularly in minimizing the side effects associated with traditional chemotherapy and ionizing radiation (IR). Recently, there has been growing interest in natural compounds for radioprotection, aiming to prevent tumor development and metastasis. Piperine, a compound found in black and long pepper, has emerged as a promising chemopreventive agent that works effectively without harming normal cells. Mechanistically, piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to IR. Combining piperine with radiotherapy offers a compelling approach, boosting treatment efficacy while protecting healthy tissues from radiation damage. Piperine's versatile role goes beyond radiosensitization to include radioprotection by inhibiting NF-κB activation, reducing autophagy, and promoting apoptosis in cancer cells. This dual action makes it a promising candidate for personalized cancer care. As research advances, the therapeutic potential of piperine may drive new frontiers in cancer treatment strategies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1007/s11033-024-09982-9
Nayara Bucair, Amana G Garrido, Kátia C C Capel, Carlos E M Bruno, Leticia Schabiuk, Marcelo V Kitahara
Background: Mobulidae is a monophyletic family within the Myliobatiformes that comprises pelagic species represented by manta and devil rays. Among the genus Mobula, the Atlantic Pygmy Devil Ray - Mobula hypostoma - is reported in coastal regions exclusively in tropical and subtropical Atlantic Ocean from 1 to 100 m deep. In Brazil, M. hypostoma is one of the least studied Mobula species. It is regularly misidentified, especially as Mobula thurstoni, and is commonly listed as bycatch, in fishery inventories, or related to opportunistic sightings in the national territory.
Methods and results: Here, we describe the complete nucleotide sequence of the mitochondrial genome (mitogenome) from Mobula hypostoma, which is 18,141 bp in length and comprises 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes. The M. hypostoma mitochondrial genes organisation and mitochondrial genome length are similar to other Mobula species, and the phylogenetic reconstruction indicates M. hypostoma as closely related to Mobula munkiana.
Conclusions: The Brazilian mitogenome of M. hypostoma is expected to be a valuable resource for molecular-based species identification, and evolutionary and phylogeography studies.
{"title":"The complete mitochondrial genome of the endangered Atlantic Pygmy Devil Ray, Mobula hypostoma (Bancroft, 1831), from Brazil.","authors":"Nayara Bucair, Amana G Garrido, Kátia C C Capel, Carlos E M Bruno, Leticia Schabiuk, Marcelo V Kitahara","doi":"10.1007/s11033-024-09982-9","DOIUrl":"https://doi.org/10.1007/s11033-024-09982-9","url":null,"abstract":"<p><strong>Background: </strong>Mobulidae is a monophyletic family within the Myliobatiformes that comprises pelagic species represented by manta and devil rays. Among the genus Mobula, the Atlantic Pygmy Devil Ray - Mobula hypostoma - is reported in coastal regions exclusively in tropical and subtropical Atlantic Ocean from 1 to 100 m deep. In Brazil, M. hypostoma is one of the least studied Mobula species. It is regularly misidentified, especially as Mobula thurstoni, and is commonly listed as bycatch, in fishery inventories, or related to opportunistic sightings in the national territory.</p><p><strong>Methods and results: </strong>Here, we describe the complete nucleotide sequence of the mitochondrial genome (mitogenome) from Mobula hypostoma, which is 18,141 bp in length and comprises 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes. The M. hypostoma mitochondrial genes organisation and mitochondrial genome length are similar to other Mobula species, and the phylogenetic reconstruction indicates M. hypostoma as closely related to Mobula munkiana.</p><p><strong>Conclusions: </strong>The Brazilian mitogenome of M. hypostoma is expected to be a valuable resource for molecular-based species identification, and evolutionary and phylogeography studies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1007/s11033-024-09985-6
Javier Fernández-Torres, Yessica Zamudio-Cuevas, Karina Martínez-Flores
Background: Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and can cause peripheral arthritis, enthesitis, and dactylitis, as well as extra-articular manifestations such as uveitis and inflammatory bowel disease. β-Defensins are antimicrobial peptides involved in the activation and regulation of several immune cell types that may influence the inflammatory response in AS. The aim was to analyze the association and interaction of two functional variants of the DEFB1 gene in AS patients, and their role with inflammatory markers.
Methods and results: The rs11362 and rs1800972 variants were genotyped using TaqMan probes in Mexican AS patients and controls. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were quantified. SPSS software was used for statistical analysis and multifactor dimensionality reduction (MDR) for interactions. The AA and GG genotypes were associated with AS risk in the age- and sex-adjusted model (OR = 6.89, P = 0.008 and OR = 3.43, P = 0.046, respectively); furthermore, the A-G haplotype showed a significant association with AS risk (OR = 2.94, P = 0.012). ESR and CRP were elevated in carriers of the AA genotype compared to the GA and GG genotypes of the rs11362 variant (20.89 ± 9.78 vs. 5.63 ± 4.61 and 4.10 ± 2.65 mm/h, P < 0.0001; and 10.92 ± 14.09 vs. 2.14 ± 2.02 and 2.15 ± 2.13 mg/L, P < 0.001, respectively). Using the MDR method, strong interactions of the rs11362 variant with sex were identified in the adjusted and unadjusted models.
Conclusions: These results suggest that the DEFB1 gene may play a key role in AS pathogenesis.
{"title":"Polymorphic variation of the DEFB1 gene might contribute to the development of ankylosing spondylitis: a preliminary study.","authors":"Javier Fernández-Torres, Yessica Zamudio-Cuevas, Karina Martínez-Flores","doi":"10.1007/s11033-024-09985-6","DOIUrl":"https://doi.org/10.1007/s11033-024-09985-6","url":null,"abstract":"<p><strong>Background: </strong>Ankylosing spondylitis (AS) is an inflammatory disease that affects the spine and can cause peripheral arthritis, enthesitis, and dactylitis, as well as extra-articular manifestations such as uveitis and inflammatory bowel disease. β-Defensins are antimicrobial peptides involved in the activation and regulation of several immune cell types that may influence the inflammatory response in AS. The aim was to analyze the association and interaction of two functional variants of the DEFB1 gene in AS patients, and their role with inflammatory markers.</p><p><strong>Methods and results: </strong>The rs11362 and rs1800972 variants were genotyped using TaqMan probes in Mexican AS patients and controls. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were quantified. SPSS software was used for statistical analysis and multifactor dimensionality reduction (MDR) for interactions. The AA and GG genotypes were associated with AS risk in the age- and sex-adjusted model (OR = 6.89, P = 0.008 and OR = 3.43, P = 0.046, respectively); furthermore, the A-G haplotype showed a significant association with AS risk (OR = 2.94, P = 0.012). ESR and CRP were elevated in carriers of the AA genotype compared to the GA and GG genotypes of the rs11362 variant (20.89 ± 9.78 vs. 5.63 ± 4.61 and 4.10 ± 2.65 mm/h, P < 0.0001; and 10.92 ± 14.09 vs. 2.14 ± 2.02 and 2.15 ± 2.13 mg/L, P < 0.001, respectively). Using the MDR method, strong interactions of the rs11362 variant with sex were identified in the adjusted and unadjusted models.</p><p><strong>Conclusions: </strong>These results suggest that the DEFB1 gene may play a key role in AS pathogenesis.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}