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Design and construction of a chimeric peptide, MeICT/IMe-AGAP, from two anti-cancer toxins of Iranian Mesobuthus eupeus scorpion. 伊朗Mesobuthus eupeus蝎两种抗癌毒素嵌合肽MeICT/IMe-AGAP的设计与构建
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.46450.1804
Razieh Seifi, Hoda Ayat, Ali Mohammad Ahadi

Scorpion venom contains various toxin peptides with pharmacological and biological properties. Scorpion toxins specifically interact with membrane ion channels which play key roles in progression of cancer. Therefore, scorpion toxins have received special attention for targeting cancer cells. Two new toxins MeICT and IMe-AGAP, isolated from Iranian yellow scorpion, Mesobuthus eupeus, interact specifically with chloride and sodium channels, respectively. Anti-cancer properties of MeICT and IMe-AGAP have been determined before, in addition they show 81 and 93% similarity with two well-known anti-cancer toxins, CTX and AGAP, respectively. The aim of this study was construction of a fusion peptide MeICT/IMe-AGAP to target different ion channels involved in cancer progression. Design and structure of the fusion peptide were investigated by bioinformatics studies. Two fragments encoding MeICT and IMe-AGAP were fused using overlapping primers by SOEing-PCR. MeICT/IMe-AGAP chimeric fragment was cloned into pET32Rh vector, expressed in Escherichia coli host and analyzed by SDS-PAGE. The in silico studies showed that chimeric peptide with GPSPG linker preserved the three-dimensional structure of both peptides and can be functional. Due to the high expression of chloride and sodium channels in various cancer cells, MeICT/IMe-AGAP fusion peptide can be used as an effective agent to target both channels in cancers, simultaneously.

蝎子毒液含有多种具有药理和生物学特性的毒素肽。蝎子毒素与在癌症进展中起关键作用的膜离子通道特异性相互作用。因此,蝎子毒素在靶向癌细胞方面受到了特别的关注。从伊朗黄蝎meobuthus eupeus中分离出两种新毒素MeICT和IMe-AGAP,分别与氯离子和钠离子通道特异性相互作用。MeICT和IMe-AGAP的抗癌特性此前已被确定,它们与两种著名的抗癌毒素CTX和AGAP的相似性分别为81%和93%。本研究的目的是构建MeICT/IMe-AGAP融合肽,以靶向参与癌症进展的不同离子通道。利用生物信息学方法对融合肽的设计和结构进行了研究。利用重叠引物将编码MeICT和time - agap的两个片段进行soing - pcr融合。将MeICT/IMe-AGAP嵌合片段克隆到pET32Rh载体中,在大肠杆菌宿主中表达,并进行SDS-PAGE分析。实验结果表明,含GPSPG连接体的嵌合肽保留了两种肽的三维结构,具有一定的功能性。由于氯离子通道和钠离子通道在多种癌细胞中的高表达,MeICT/IMe-AGAP融合肽可以作为一种有效的药物同时靶向两种通道。
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引用次数: 0
The genetic polymorphisms at the promoter region of HLA-DQB1 gene, creating responsive elements for NF1/CTF and converting the TFII-D binding site to GR-alpha. HLA-DQB1基因启动子区域的遗传多态性,产生NF1/CTF的应答元件,并将TFII-D结合位点转化为gr - α。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.46890.1813
Khyber Saify

Human leukocyte antigen-DQB1 (HLA-DQB1, OMIM: 604305) is the human major histocompatibility complex (MHC) system. HLA genes are classified into three classes (I, II, and III). The HLA-DQB1 belongs to class II, is mainly involved in the actions of the human immune system and plays a fundamental role in donor-recipient matching in transplantation and can be associated with most autoimmune diseases. In this study, the potential influence(s) of the G-71C (rs71542466) and T-80C (rs9274529) genetic polymorphisms were investigated. These polymorphisms, located in the HLA-DQB1 promoter region, have a significant frequency in the world population. The online software ALGGEN-PROMO.v8.3 was used in this work. The results indicate that the C allele at the -71 position actually creates a new potential binding site for NF1/CTF and the C allele at the -80 position changes the TFII-D binding site into a GR-alpha response element. The NF1/CTF plays the role of activator and the GR-alpha is the inhibitor; thus, according to the roles of these transcription factors, it is suggested that the above-mentioned polymorphisms alter the expression levels of HLA-DQB1. Therefore, this genetic variation is associated with autoimmune diseases; however, this cannot be generalized because this is the first report and more studies are needed in the future.

人白细胞抗原- dqb1 (HLA-DQB1, OMIM: 604305)是人主要组织相容性复合体(MHC)系统。HLA基因分为I、II、III三类,其中HLA- dqb1属于II类,主要参与人体免疫系统的活动,在移植供体-受体匹配中起基础作用,与大多数自身免疫性疾病有关。本研究探讨了G-71C (rs71542466)和T-80C (rs9274529)遗传多态性的潜在影响。这些多态性位于HLA-DQB1启动子区域,在世界人群中具有显著的频率。本工作使用在线软件ALGGEN-PROMO.v8.3。结果表明,位于-71位的C等位基因实际上为NF1/CTF创造了一个新的潜在结合位点,而位于-80位的C等位基因将TFII-D结合位点改变为gr - α响应元件。NF1/CTF为活化剂,gr - α为抑制剂;因此,根据这些转录因子的作用,我们认为上述多态性改变了HLA-DQB1的表达水平。因此,这种遗传变异与自身免疫性疾病有关;然而,这并不能一概而论,因为这是第一份报告,未来还需要更多的研究。
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引用次数: 0
Toxicity and autophagy effects of fluorinated cycloplatinated(II) complex bearing dppm ligand on cancer cells in in-vitro culture and in-silico prediction. 含dppm配体的氟化环铂(II)配合物对癌细胞的体外培养和计算机预测的毒性和自噬作用。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.44705.1781
Zahra Kamalzade, Elham Hoveizi, Masood Fereidoonnezhad

Toxicity and autophagy effects of a new complex of platinum II (CPC) were evaluated on HeLa cells cultured on a PCL/gelatin electrospinning scaffold. HeLa cells were treated with CPC on the first, third, and fifth days and the concentration of IC50 was determined. The autophagic and apoptotic effects of CPC were examined by MTT assay, Acridine Orange, Giemsa, DAPI, MDC, real-time PCR, Western blot testing, and molecular docking. The cell viability was obtained on days 1, 3, and 5 as much as 50, 7.28, and 19%, respectively with a concentration of IC50 (100μM) of CPC. The staining results indicated that the treatment of HeLa cells with CPC had antitumor and autophagic effects. Results of RT-PCR showed that the expression of BAX, BAD, P53, and LC3 genes was significantly increased in the sample treated with IC50 concentration compared to the control sample whereas the expression of BCL2, mTOR, and ACT genes in cells was significantly decreased compared to the control group. Also, these results were confirmed by Western blotting. The data indicated the induction of apoptotic death and autophagy in the studied cells. The new compound of CPC has antitumor effects.

研究了新型铂复合物(CPC)对PCL/明胶静电纺丝支架上培养的HeLa细胞的毒性和自噬作用。CPC分别于第1、3、5天作用于HeLa细胞,测定IC50浓度。采用MTT法、吖啶橙法、Giemsa法、DAPI法、MDC法、实时PCR法、Western blot法、分子对接法检测CPC的自噬和凋亡作用。CPC浓度为IC50 (100μM)时,第1天、第3天和第5天细胞存活率分别为50%、7.28%和19%。染色结果表明,CPC对HeLa细胞具有抗肿瘤和自噬作用。RT-PCR结果显示,与对照组相比,IC50浓度处理后的细胞中BAX、BAD、P53和LC3基因的表达量显著增加,而BCL2、mTOR和ACT基因的表达量显著降低。Western blotting也证实了这些结果。结果表明,该药物可诱导细胞凋亡和自噬。该新化合物具有抗肿瘤作用。
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引用次数: 0
Detection of Hepatozoon spp. in dogs in Shiraz, southern Iran and its effects on the hematological alterations. 伊朗南部设拉子犬肝虫的检测及其对血液学改变的影响。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47151.1821
Ehsan Zoaktafi, Hassan Sharifiyazdi, Nooshin Derakhshandeh, Farnoosh Bakhshaei-Shahrbabaki

Canine hepatozoonosis is a tick-transmitted apicomplexan infection caused by two species of Hepatozoon, H. canis, and H. americanum. The present research aimed at detection of Hepatozoon spp. in dogs and its effects on hematological alterations. Blood samples were taken from 108 dogs to assess Hepatozoon spp. Phylogenetic analysis was performed based on the 18S rDNA marker by PCR assay and Giemsa-stained blood smear examination. Of the 108 blood samples of dogs tested in the present study, eight (7.40%, 95% CI: 3.25-14.07%) were positive by the Hepatozoon-specific PCR assay. However, in the microscopic examination, only one sample (0.93%) was positive. All of the sequenced samples were H. canis. The Hepatozoon sequences obtained from PCR amplicons in the canine-positive cases exhibited 100% similarity to each other and 98.47-100% similarity to other relevant sequences in GenBank. These findings represent the first molecular evidence of H. canis in dog populations in South Iran. Furthermore, according to the hematological analysis, significantly higher average numbers of neutrophils and lymphocytes were found in the infected group compared to the non-infected dogs. In this study, no statistically significant connection (P<0.05) was observed between H. canis infection and the examined risk factors.

犬肝人畜共患病是一种蜱传播的顶端复杂感染,由犬肝人畜共患病和美洲肝人畜共患病两种引起。本研究旨在检测犬肝虫及其对血液学改变的影响。方法采集108只狗的血样,采用PCR法和吉姆萨染色血涂片法,采用18S rDNA标记进行系统发育分析。在本研究检测的108份狗的血液样本中,8份(7.40%,95% CI: 3.25-14.07%)的肝虫特异性PCR检测呈阳性。但镜检中仅有1例(0.93%)呈阳性。所有测序样本均为犬人。从犬阳性病例的PCR扩增物中获得的Hepatozoon序列彼此之间的相似性为100%,与GenBank中其他相关序列的相似性为98.47-100%。这些发现是伊朗南部犬类中首次出现犬嗜血杆菌的分子证据。此外,根据血液学分析,感染组的中性粒细胞和淋巴细胞的平均数量明显高于未感染的狗。在本研究中,犬链球菌感染与检查的危险因素没有统计学意义上的联系。
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引用次数: 0
Evaluating the association of rs6983267 polymorphism of the CCAT2 gene with thyroid cancer susceptibility in the Iranian Azeri population. 评估CCAT2基因rs6983267多态性与伊朗阿塞拜疆人群甲状腺癌易感性的关系
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47622.1839
Masoud Jabraili, Solmaz Moniri-Javadhesari, Nasser Pouladi, Mohammad Ali Hosseinpour-Feizi

Thyroid cancer is the most common malignancy of the endocrine system. LncRNAs play critical role in various cellular processes and are associated with several diseases. CCAT2 is a lncRNA molecule overexpressed in thyroid cancer. Single nucleotide polymorphisms in CCAT2 gene can cause changes in the structure and function of CCAT2 transcripts and susceptibility to several diseases. This study aimed to evaluate the association of rs6983267 in CCAT2 gene with thyroid cancer susceptibility in the Azeri population of Iran. In this "case-control" study, genomic DNA was extracted from peripheral blood of 102 individuals affected by thyroid cancer and 103 healthy individuals as controls. Genotyping was performed using TETRA-ARMS polymerase chain reaction. Statistical analysis showed no significant association between genotypes and/or alleles with the occurrence of thyroid cancer in the studied population, patients' gender, and tumor type. Nevertheless, we found that the allelic and genotypic distribution of this SNP was associated with the size of thyroid tumors in patients. It is assumed that investigating more individuals from both case and control group may further determine the genotypic and allelic frequencies of this SNP locus in Iranian-Azeri population.

甲状腺癌是内分泌系统最常见的恶性肿瘤。lncrna在多种细胞过程中发挥关键作用,并与多种疾病相关。CCAT2是一种在甲状腺癌中过表达的lncRNA分子。CCAT2基因的单核苷酸多态性可引起CCAT2转录本结构和功能的改变以及对多种疾病的易感性。本研究旨在评估CCAT2基因rs6983267与伊朗Azeri人群甲状腺癌易感性的关系。在这项“病例对照”研究中,从102名甲状腺癌患者和103名健康人的外周血中提取基因组DNA作为对照。采用TETRA-ARMS聚合酶链反应进行基因分型。统计分析显示,基因型和/或等位基因与研究人群中甲状腺癌的发生、患者的性别和肿瘤类型均无显著相关性。然而,我们发现该SNP的等位基因和基因型分布与患者甲状腺肿瘤的大小有关。假设对病例和对照组中更多的个体进行调查,可以进一步确定伊朗-阿塞拜疆人群中该SNP位点的基因型和等位基因频率。
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引用次数: 0
Human BKV large T genome detection in prostate cancer and benign prostatic hyperplasia tissue samples by nested PCR: A case-control study. 用套式PCR检测前列腺癌症和良性前列腺增生组织样本中的人类BKV大T基因组:一项病例对照研究。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47537.1836
Narges Tavassoli, Arastoo Vojdani, Sara Salimi-Namin, Majid Khadem-Rezaiyan, Mahmoudreza Kalantari, Masoud Youssefi

Human BK polyomavirus (BKPyV) is a latent infectious agent in the genitourinary tract associated with hemorrhagic cystitis and nephropathy. This virus can be a risk factor for various human malignancies, including prostate cancer (PCa). It may contribute to prostate cancer development, as it demonstrates oncogenic properties by encoding oncoproteins. This study assessed the prevalence of this virus in benign and malignant prostate tissues. Between 2009 and 2019, 49 formalin-fixed paraffin-embedded (FFPE) PCa and 49 benign prostatic hyperplasia (BPH) samples were gathered from the pathology department of a tertiary care university hospital. They were used as cases and controls, respectively. After deparaffinization and DNA extraction, nested PCR was applied to identify the BKPyVgp5 gene (LTAg) using inner and outer primers. The nested PCR showed a 278-bp bond corresponding to the BKPyVgp5 genome (LTAg) in 53.1% (26/49) of PCa and 14.3% (7/49) of BPH (p<0.001). The presence of BKV was significantly associated with an increased risk of PCa development (OR=6.78, 95% CI=2.55-18.02, p<0.001). The BKV LTAg gene was significantly more prevalent in PCa samples than in BPH samples. These results demonstrate the presence of the virus in prostate cancer tissues.

人类BK多瘤病毒(BKPyV)是泌尿生殖道中与出血性膀胱炎和肾病相关的潜在传染源。这种病毒可能是多种人类恶性肿瘤的危险因素,包括癌症(PCa)。它可能有助于前列腺癌症的发展,因为它通过编码癌蛋白来证明致癌特性。这项研究评估了这种病毒在良性和恶性前列腺组织中的患病率。2009年至2019年间,从一所三级护理大学医院的病理科采集了49份福尔马林固定石蜡包埋(FFPE)前列腺癌和49份良性前列腺增生(BPH)样本。它们分别被用作病例和对照。在脱亲和和DNA提取后,使用内外引物应用套式PCR来鉴定BKPyVgp5基因(LTAg)。巢式PCR在53.1%(26/49)的前列腺癌和14.3%(7/49)的前列腺增生中显示与BKPyVgp5基因组(LTAg)对应的278bp的键(p
{"title":"Human BKV large T genome detection in prostate cancer and benign prostatic hyperplasia tissue samples by nested PCR: A case-control study.","authors":"Narges Tavassoli,&nbsp;Arastoo Vojdani,&nbsp;Sara Salimi-Namin,&nbsp;Majid Khadem-Rezaiyan,&nbsp;Mahmoudreza Kalantari,&nbsp;Masoud Youssefi","doi":"10.22099/mbrc.2023.47537.1836","DOIUrl":"10.22099/mbrc.2023.47537.1836","url":null,"abstract":"<p><p>Human BK polyomavirus (BKPyV) is a latent infectious agent in the genitourinary tract associated with hemorrhagic cystitis and nephropathy. This virus can be a risk factor for various human malignancies, including prostate cancer (PCa). It may contribute to prostate cancer development, as it demonstrates oncogenic properties by encoding oncoproteins. This study assessed the prevalence of this virus in benign and malignant prostate tissues. Between 2009 and 2019, 49 formalin-fixed paraffin-embedded (FFPE) PCa and 49 benign prostatic hyperplasia (BPH) samples were gathered from the pathology department of a tertiary care university hospital. They were used as cases and controls, respectively. After deparaffinization and DNA extraction, nested PCR was applied to identify the BKPyVgp5 gene (LTAg) using inner and outer primers. The nested PCR showed a 278-bp bond corresponding to the BKPyVgp5 genome (LTAg) in 53.1% (26/49) of PCa and 14.3% (7/49) of BPH (p<0.001). The presence of BKV was significantly associated with an increased risk of PCa development (OR=6.78, 95% CI=2.55-18.02, p<0.001). The BKV LTAg gene was significantly more prevalent in PCa samples than in BPH samples. These results demonstrate the presence of the virus in prostate cancer tissues.</p>","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":"12 4","pages":"149-154"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular mimicry and COVID-19: Potential implications for global fertility. 分子拟态和 COVID-19:对全球生育率的潜在影响。
IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47122.1819
Custer C Deocaris, Malona V Alinsug

There has been a concerning increase in the incidence of autoimmune diseases following SARS-CoV-2 infection, with molecular mimicry proposed as a potential mechanism. Our study identified nine fertility-associated proteins (AMH, BMP2, CUBN, DNER, ERCC1, KASH5, MSLN, TPO, and ZP3) that exhibit potential molecular mimicry with MHC-II epitopes of SARS-CoV-2 proteins (N, ORF1A, ORF1AB, and S). We screened for epitopes based on in silico binding using DR-, DQ-, and DP-haplotypes that predispose susceptible individuals to autoimmune diseases. Our systematic analysis revealed that 41 countries with population coverage of over 50% had a pre-COVID pandemic total fertility rate of less than 2.1 births per woman. With over 761 million people from 229 countries and territories infected since December 2019, there may be a potential for a foreseeable negative effect on fertility in specific countries, particularly in high-income economies experiencing rapid demographic changes.

感染 SARS-CoV-2 后,自身免疫性疾病的发病率有所上升,这令人担忧,而分子模拟被认为是一种潜在的机制。我们的研究发现九种生育相关蛋白(AMH、BMP2、CUBN、DNER、ERCC1、KASH5、MSLN、TPO 和 ZP3)与 SARS-CoV-2 蛋白(N、ORF1A、ORF1AB 和 S)的 MHC-II 表位具有潜在的分子模拟作用。我们利用易患自身免疫性疾病的 DR-、DQ- 和 DP-单倍型进行了表位的硅结合筛选。我们的系统分析显示,41 个人口覆盖率超过 50%的国家在 COVID 流行前的总生育率低于每名妇女 2.1 胎。自 2019 年 12 月以来,229 个国家和地区的超过 7.61 亿人受到感染,这可能会对特定国家的生育率产生可预见的负面影响,尤其是在经历快速人口结构变化的高收入经济体。
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引用次数: 0
Сytotoxic effect of CAR-T cells against modified MCF-7 breast cancer cell line. CAR-T细胞对改良MCF-7乳腺癌症细胞系的细胞毒性作用。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47125.1820
Aigul Kh Valiullina, Ekaterina A Zmievskaya, Irina A Ganeeva, Margarita N Zhuravleva, Ekaterina E Garanina, Albert A Rizvanov, Alexey V Petukhov, Emil R Bulatov

The most often diagnosed and fatal malignancy in women is breast cancer. The International Agency for Research on Cancer (IARC) estimates that there are 2.26 million new cases of cancer in 2020. Adoptive cell therapy using T cells with chimeric antigen receptor shows potential for the treatment of solid tumors, such as breast cancer. In this work the effectiveness of CAR-T cells against monolayer and three-dimensional bioprinted tumor-like structures made of modified MCF-7 breast cancer cells was assessed. The cytokine profile of supernatants after co-cultivation of MCF-7 tumor cell models with CAR-T cells was also measured to reveal the inflammatory background associated with this interaction.

女性最常被诊断和致命的恶性肿瘤是乳腺癌症。国际癌症研究机构(IARC)估计,2020年癌症新增病例226万例。使用具有嵌合抗原受体的T细胞的过继细胞疗法显示出治疗实体瘤(如乳腺癌症)的潜力。在这项工作中,评估了CAR-T细胞对抗由修饰的MCF-7乳腺癌症细胞制成的单层和三维生物打印肿瘤样结构的有效性。还测量了MCF-7肿瘤细胞模型与CAR-T细胞共培养后上清液的细胞因子谱,以揭示与这种相互作用相关的炎症背景。
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引用次数: 0
Structural arrangement of the active back-to-back dimer in N-glycosylated ErbB receptors is regulated by heterodimerization. n -糖基化ErbB受体中活性背对背二聚体的结构排列受异源二聚化调节。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.47147.1822
Romina Mashayekh-Poul, Maryam Azimzadeh-Irani, Seyedeh Zeinab Masoomi-Nomandan

The human epidermal growth factor receptor (EGFR/ErbB) family consists of four members (ErbB1-4) and belongs to the superfamily of receptor tyrosine kinases (RTKs). The ErbB family members participate in multiple cellular pathways and are the key players in several cancers (brain, breast, lung etc.). Activation of these family members depends on their extracellular domains forming back-to-back hetero/homo dimers. Moreover, dimers are glycosylated, which is a crucial post-translational modification that affects the conformation and function of the protein. Here, molecular modeling and molecular docking are used to comprehensively investigate the dimerization mechanism in glycosylated back-to-back active dimer formation in the entire ErbB receptors for the first time. Results showed that 21 out of 37 clusters of active back-to-back dimers formed by all family members are through heterodimerization. Including; ErbB1-ErbB3/ErbB4, ErbB2-ErbB3/ErbB4 and ErbB3-ErbB4. Ranking ErbB2-ErbB3 as the most stabilized back-to-back dimeric construct. While glycan arrangements favor both homo/hetero dimerization at the dimeric interfaces, it promotes heterodimerization by stabilizing and packing the ligand binding sites of EGFR and ErbB2 respectively. These findings pave the path to future heterodimeric interface/glycan targeting rational anti-cancer drug designs for ErbB receptors.

人表皮生长因子受体(EGFR/ErbB)家族由四个成员(ErbB1-4)组成,属于受体酪氨酸激酶(RTKs)超家族。ErbB家族成员参与多种细胞通路,是多种癌症(脑癌、乳腺癌、肺癌等)的关键参与者。这些家族成员的激活依赖于它们的细胞外结构域形成背靠背的异性/同性二聚体。此外,二聚体被糖基化,这是一个关键的翻译后修饰,影响蛋白质的构象和功能。本文首次采用分子模拟和分子对接的方法,全面研究了整个ErbB受体中糖基化背靠背活性二聚体形成的二聚化机制。结果表明,所有家族成员形成的37个活性背靠背二聚体簇中有21个是通过异源二聚形成的。包括;ErbB1-ErbB3/ErbB4, ErbB2-ErbB3/ErbB4和ErbB3-ErbB4。ErbB2-ErbB3是最稳定的背靠背二聚体结构。虽然聚糖的排列有利于二聚体界面上的同源/异质二聚化,但它通过分别稳定和包装EGFR和ErbB2的配体结合位点来促进异源二聚化。这些发现为未来设计针对ErbB受体的异二聚体界面/聚糖靶向的合理抗癌药物铺平了道路。
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引用次数: 0
The molecular characteristics of colorectal cancer: Impact of Ibuprofen and hyperthermia. 结直肠癌的分子特征:布洛芬和热疗的影响。
IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-01 DOI: 10.22099/mbrc.2023.45296.1802
Farzaneh Zarghampoor, Behnaz Valibeigi, Abbas Behzad-Behbahani

Despite various treatment options available for colorectal cancer, the survival rates for patients remain low. This study investigated the effects of hyperthermia and Ibuprofen on human colorectal adenocarcinoma cells (HT-29) viability, proliferation, and gene expression related to tumor suppression, Wnt signaling pathways, proliferation, and apoptosis The cells were exposed to hyperthermia at 42 or 43°C for 3 hours or Ibuprofen at different concentrations (700-1500 μM), and the effects were analyzed through MTT assay, trypan blue staining, and quantitative Real-time PCR. The study used quantitative Real-time PCR (qRT-PCR) to evaluate the effect of hyperthermia and Ibuprofen on the expression of various genes associated with tumor suppression, proliferation, Wnt signaling pathway, and apoptosis. The results revealed that hyperthermia caused a minor reduction in the viability and proliferation of HT-29 cells, but the decrease was not statistically significant (P<0.05). On the other hand, Ibuprofen caused a concentration-dependent decrease in the viability and proliferation of HT-29 cells. Both hyperthermia and Ibuprofen reduced the expression of WNT1, CTNNB1, BCL2, and PCNA genes, and increased the expression of KLF4, P53, and BAX genes. However, the changes in gene expression were not statistically significant in cells treated with hyperthermia. The findings suggest that Ibuprofen is more effective in reducing cancer cell proliferation by promoting apoptosis and inhibiting the Wnt signaling pathway than hyperthermia, which had some impact but was not statistically significant. The study highlights the potential of Ibuprofen as a targeted therapy for colorectal cancer.

尽管结直肠癌有多种治疗选择,但患者的存活率仍然很低。本实验研究热疗和布洛芬对人结直肠癌腺癌细胞(HT-29)活力、增殖、抑瘤相关基因表达、Wnt信号通路、增殖和凋亡的影响。将细胞分别置于42°C或43°C热疗3 h或不同浓度布洛芬(700 ~ 1500 μM)下,通过MTT法、台潘蓝染色和定量Real-time PCR分析其影响。本研究采用实时荧光定量PCR (quantitative Real-time PCR, qRT-PCR)评价热疗和布洛芬对肿瘤抑制、增殖、Wnt信号通路和凋亡相关基因表达的影响。结果显示,热疗引起HT-29细胞活力和增殖能力的轻微降低,但PWNT1、CTNNB1、BCL2和PCNA基因的降低无统计学意义,KLF4、P53和BAX基因的表达升高。然而,在高温处理的细胞中,基因表达的变化没有统计学意义。研究结果提示,与热疗相比,布洛芬通过促进细胞凋亡和抑制Wnt信号通路减少癌细胞增殖更有效,有一定影响,但无统计学意义。这项研究强调了布洛芬作为结直肠癌靶向治疗的潜力。
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引用次数: 0
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