Seaweeds have been utilized as food, fodder, fertilizer, and medicine since ancient times; nevertheless, they have received only a little attention. In the current work, we extracted the sulfated polysaccharide from a marine source and investigated its anti-arthritic potential in vivo. The isolated and freeze-dried polysaccharide was tested for acute oral toxicity based on OECD 423. This step was followed by investigations on clinical signs and gross pathological alterations seen. A complete Freund's adjuvant-induced arthritis was used to test the in vivo activity in female Sprague-Dawley rats, which were divided into five groups: (1) normal control, (2) arthritic control, (3) methotrexate treatment (0.1 mg/kg), (4) crude sulfated polysaccharide (CSP) (5 mg/kg), and (5) CSP (10 mg/kg). CSP was from the marine brown algae Sargassum ilicifolium from the Gulf of Mannar. The body weight, paw volume, and biochemical markers (alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein levels) were also measured for each group coupled with histopathological and immunohistochemistry studies. The acute toxicity investigation indicated that the lethal dose of 50% (LD50) of the polysaccharide was more than 2,000 mg/kg. In addition, animals from the methotrexate and CSP (5 mg/kg, p.o.) groups had a substantial reduction in paw volume compared to other treatment groups. Methotrexate and CSP treatment dramatically decreased the levels of the investigated marker enzymes. Histopathology revealed that low-dose CSP (5 mg/kg, p.o.) significantly reduced the severity of synovitis, panniculitis, liver necrosis, inflammatory cell infiltration, and cortical and paracortical necrotic foci in node, compared to the high dose (10 mg/kg, p.o.). Immunohistochemical studies revealed that CSP (5 mg/kg) significantly inhibited pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-2, and CD4 cells. Overall, it can be concluded that a low-dose CSP (5 mg/kg) is an efficient anti-arthritic agent that confers its effects via the cytokine pathway.
{"title":"Anti-arthritic potential of crude sulfated polysaccharide from marine macroalgae <i>Sargassum ilicifolium</i> (Turner) C. Agardh: Regulation of cytokine cascade.","authors":"Lavanya Ramamoorthi, Srikanth Jeyabalan, Seethalakshmi Sankar, M Yasmin Begum, Chamundeeswari Duraipandian, Mahendran Sekar, Ling Shing Wong, Vetriselvan Subramaniyan","doi":"10.1515/bmc-2022-0050","DOIUrl":"https://doi.org/10.1515/bmc-2022-0050","url":null,"abstract":"<p><p>Seaweeds have been utilized as food, fodder, fertilizer, and medicine since ancient times; nevertheless, they have received only a little attention. In the current work, we extracted the sulfated polysaccharide from a marine source and investigated its anti-arthritic potential <i>in vivo</i>. The isolated and freeze-dried polysaccharide was tested for acute oral toxicity based on OECD 423. This step was followed by investigations on clinical signs and gross pathological alterations seen. A complete Freund's adjuvant-induced arthritis was used to test the <i>in vivo</i> activity in female Sprague-Dawley rats, which were divided into five groups: (1) normal control, (2) arthritic control, (3) methotrexate treatment (0.1 mg/kg), (4) crude sulfated polysaccharide (CSP) (5 mg/kg), and (5) CSP (10 mg/kg). CSP was from the marine brown algae <i>Sargassum ilicifolium</i> from the Gulf of Mannar. The body weight, paw volume, and biochemical markers (alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein levels) were also measured for each group coupled with histopathological and immunohistochemistry studies. The acute toxicity investigation indicated that the lethal dose of 50% (LD<sub>50</sub>) of the polysaccharide was more than 2,000 mg/kg. In addition, animals from the methotrexate and CSP (5 mg/kg, p.o.) groups had a substantial reduction in paw volume compared to other treatment groups. Methotrexate and CSP treatment dramatically decreased the levels of the investigated marker enzymes. Histopathology revealed that low-dose CSP (5 mg/kg, p.o.) significantly reduced the severity of synovitis, panniculitis, liver necrosis, inflammatory cell infiltration, and cortical and paracortical necrotic foci in node, compared to the high dose (10 mg/kg, p.o.). Immunohistochemical studies revealed that CSP (5 mg/kg) significantly inhibited pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-2, and CD4 cells. Overall, it can be concluded that a low-dose CSP (5 mg/kg) is an efficient anti-arthritic agent that confers its effects via the cytokine pathway.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0051
John Dawi, Scarlet Affa, Yura Misakyan, Sabrina Fardeheb, Samuel Kades, Anthony Kiriaki, Aishvaryaa Shree Mohan, Brandon Norris, Sonyeol Yoon, Vishwanath Venketaraman
Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes.
{"title":"Exploring cardiovascular implications in systemic lupus erythematosus: A holistic analysis of complications, diagnostic criteria, and therapeutic modalities, encompassing pharmacological and adjuvant approaches.","authors":"John Dawi, Scarlet Affa, Yura Misakyan, Sabrina Fardeheb, Samuel Kades, Anthony Kiriaki, Aishvaryaa Shree Mohan, Brandon Norris, Sonyeol Yoon, Vishwanath Venketaraman","doi":"10.1515/bmc-2022-0051","DOIUrl":"10.1515/bmc-2022-0051","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0049
Mahmoud S Abdelmoneim, Elsayed E Hafez, Mona F A Dawood, Sherif F Hammad, Mohamed A Ghazy
Bisphenol A (BPA) and p-nitrophenol (PNP) are emerging contaminants of soils due to their wide presence in agricultural and industrial products. Thus, the present study aimed to integrate morpho-physiological, ionic homeostasis, and defense- and antioxidant-related genes in the response of tomato plants to BPA or PNP stress, an area of research that has been scarcely studied. In this work, increasing the levels of BPA and PNP in the soil intensified their drastic effects on the biomass and photosynthetic pigments of tomato plants. Moreover, BPA and PNP induced osmotic stress on tomato plants by reducing soluble sugars and soluble proteins relative to control. The soil contamination with BPA and PNP treatments caused a decline in the levels of macro- and micro-elements in the foliar tissues of tomatoes while simultaneously increasing the contents of non-essential micronutrients. The Fourier transform infrared analysis of the active components in tomato leaves revealed that BPA influenced the presence of certain functional groups, resulting in the absence of some functional groups, while on PNP treatment, there was a shift observed in certain functional groups compared to the control. At the molecular level, BPA and PNP induced an increase in the gene expression of polyphenol oxidase and peroxidase, with the exception of POD gene expression under BPA stress. The expression of the thaumatin-like protein gene increased at the highest level of PNP and a moderate level of BPA without any significant effect of both pollutants on the expression of the tubulin (TUB) gene. The comprehensive analysis of biochemical responses in tomato plants subjected to BPA and PNP stress illustrates valuable insights into the mechanisms underlying tolerance to these pollutants.
双酚 A(BPA)和对硝基苯酚(PNP)是土壤中新出现的污染物,因为它们广泛存在于农产品和工业产品中。因此,本研究旨在整合番茄植物对双酚 A 或对硝基苯酚胁迫的反应中的形态生理、离子平衡以及防御和抗氧化相关基因,这是一个鲜有研究的领域。在这项研究中,土壤中双酚 A 和全氟辛基苯酚含量的增加加剧了它们对番茄植株生物量和光合色素的剧烈影响。此外,与对照组相比,BPA 和 PNP 会降低可溶性糖和可溶性蛋白质,从而诱发番茄植株的渗透胁迫。双酚 A 和 PNP 污染土壤会导致番茄叶片组织中的宏量和微量元素含量下降,同时增加非必需微量元素的含量。对番茄叶片中有效成分的傅立叶变换红外分析表明,双酚 A 影响了某些官能团的存在,导致某些官能团缺失,而在 PNP 处理中,与对照组相比,某些官能团发生了变化。在分子水平上,双酚 A 和 PNP 诱导了多酚氧化酶和过氧化物酶基因表达的增加,只有 POD 基因表达在双酚 A 胁迫下有所增加。在最高水平的 PNP 和中等水平的双酚 A 诱导下,thaumatin 样蛋白基因的表达增加,而这两种污染物对微管蛋白(TUB)基因的表达没有明显影响。对受到 BPA 和 PNP 胁迫的番茄植株的生化反应进行全面分析,有助于深入了解这些污染物的耐受机制。
{"title":"Toxicity of bisphenol A and <i>p</i>-nitrophenol on tomato plants: Morpho-physiological, ionomic profile, and antioxidants/defense-related gene expression studies.","authors":"Mahmoud S Abdelmoneim, Elsayed E Hafez, Mona F A Dawood, Sherif F Hammad, Mohamed A Ghazy","doi":"10.1515/bmc-2022-0049","DOIUrl":"https://doi.org/10.1515/bmc-2022-0049","url":null,"abstract":"<p><p>Bisphenol A (BPA) and <i>p</i>-nitrophenol (PNP) are emerging contaminants of soils due to their wide presence in agricultural and industrial products. Thus, the present study aimed to integrate morpho-physiological, ionic homeostasis, and defense- and antioxidant-related genes in the response of tomato plants to BPA or PNP stress, an area of research that has been scarcely studied. In this work, increasing the levels of BPA and PNP in the soil intensified their drastic effects on the biomass and photosynthetic pigments of tomato plants. Moreover, BPA and PNP induced osmotic stress on tomato plants by reducing soluble sugars and soluble proteins relative to control. The soil contamination with BPA and PNP treatments caused a decline in the levels of macro- and micro-elements in the foliar tissues of tomatoes while simultaneously increasing the contents of non-essential micronutrients. The Fourier transform infrared analysis of the active components in tomato leaves revealed that BPA influenced the presence of certain functional groups, resulting in the absence of some functional groups, while on PNP treatment, there was a shift observed in certain functional groups compared to the control. At the molecular level, BPA and PNP induced an increase in the gene expression of polyphenol oxidase and peroxidase, with the exception of POD gene expression under BPA stress. The expression of the thaumatin-like protein gene increased at the highest level of PNP and a moderate level of BPA without any significant effect of both pollutants on the expression of the tubulin (TUB) gene. The comprehensive analysis of biochemical responses in tomato plants subjected to BPA and PNP stress illustrates valuable insights into the mechanisms underlying tolerance to these pollutants.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0027
Liberty T Navhaya, Dzveta Mutsawashe Blessing, Mthembu Yamkela, Sesethu Godlo, Xolani Henry Makhoba
Coronavirus disease 2019 (COVID-19) is a novel disease that had devastating effects on human lives and the country's economies worldwide. This disease shows similar parasitic traits, requiring the host's biomolecules for its survival and propagation. Spike glycoproteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 spike protein) located on the surface of the COVID-19 virus serve as a potential hotspot for antiviral drug development based on their structure. COVID-19 virus calls into action the chaperonin system that assists the attacker, hence favoring infection. To investigate the interaction that occurs between SARS-CoV-2 spike protein and human molecular chaperons (HSPA8 and sHSP27), a series of steps were carried out which included sequence attainment and analysis, followed by multiple sequence alignment, homology modeling, and protein-protein docking which we performed using Cluspro to predict the interactions between SARS-CoV-2 spike protein and human molecular chaperones of interest. Our findings depicted that SARS-CoV-2 spike protein consists of three distinct chains, chains A, B, and C, which interact forming hydrogen bonds, hydrophobic interactions, and electrostatic interactions with both human HSPA8 and HSP27 with -828.3 and -827.9 kcal/mol as binding energies for human HSPA8 and -1166.7 and -1165.9 kcal/mol for HSP27.
{"title":"A comprehensive review of the interaction between COVID-19 spike proteins with mammalian small and major heat shock proteins.","authors":"Liberty T Navhaya, Dzveta Mutsawashe Blessing, Mthembu Yamkela, Sesethu Godlo, Xolani Henry Makhoba","doi":"10.1515/bmc-2022-0027","DOIUrl":"10.1515/bmc-2022-0027","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is a novel disease that had devastating effects on human lives and the country's economies worldwide. This disease shows similar parasitic traits, requiring the host's biomolecules for its survival and propagation. Spike glycoproteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 spike protein) located on the surface of the COVID-19 virus serve as a potential hotspot for antiviral drug development based on their structure. COVID-19 virus calls into action the chaperonin system that assists the attacker, hence favoring infection. To investigate the interaction that occurs between SARS-CoV-2 spike protein and human molecular chaperons (HSPA8 and sHSP27), a series of steps were carried out which included sequence attainment and analysis, followed by multiple sequence alignment, homology modeling, and protein-protein docking which we performed using Cluspro to predict the interactions between SARS-CoV-2 spike protein and human molecular chaperones of interest. Our findings depicted that SARS-CoV-2 spike protein consists of three distinct chains, chains A, B, and C, which interact forming hydrogen bonds, hydrophobic interactions, and electrostatic interactions with both human HSPA8 and HSP27 with -828.3 and -827.9 kcal/mol as binding energies for human HSPA8 and -1166.7 and -1165.9 kcal/mol for HSP27.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0048
Ernesto Alonso Lagarda-Clark, Charles Goulet, Arturo Duarte-Sierra
The lifecycle of fresh produce involves a sequence of biochemical events during their ontology, and these events are particularly significant for climacteric fruits. A high demand during ripening is observed in these plant products, which is reflected in a high rate of respiration and ethylene production. Increased respiratory demand triggers the activation of secondary pathways such as alternate oxidase, which do not experience critical increases in energy consumption in non-climacteric fruit. In addition, biochemical events produced by external factors lead to compensatory responses in fresh produce to counteract the oxidative stress caused by the former. The dynamics of these responses are accompanied by signaling, where reactive oxygen species play a pivotal role in fresh product cell perception. This review aims to describe the protection mechanisms of fresh produce against environmental challenges and how controlled doses of abiotic stressors can be used to improve quality and prolong their shelf-life through the interaction of stress and defense mechanisms.
{"title":"Biochemical dynamics during postharvest: Highlighting the interplay of stress during storage and maturation of fresh produce.","authors":"Ernesto Alonso Lagarda-Clark, Charles Goulet, Arturo Duarte-Sierra","doi":"10.1515/bmc-2022-0048","DOIUrl":"https://doi.org/10.1515/bmc-2022-0048","url":null,"abstract":"<p><p>The lifecycle of fresh produce involves a sequence of biochemical events during their ontology, and these events are particularly significant for climacteric fruits. A high demand during ripening is observed in these plant products, which is reflected in a high rate of respiration and ethylene production. Increased respiratory demand triggers the activation of secondary pathways such as alternate oxidase, which do not experience critical increases in energy consumption in non-climacteric fruit. In addition, biochemical events produced by external factors lead to compensatory responses in fresh produce to counteract the oxidative stress caused by the former. The dynamics of these responses are accompanied by signaling, where reactive oxygen species play a pivotal role in fresh product cell perception. This review aims to describe the protection mechanisms of fresh produce against environmental challenges and how controlled doses of abiotic stressors can be used to improve quality and prolong their shelf-life through the interaction of stress and defense mechanisms.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0047
Maxwell S DeNies, Allen P Liu, Santiago Schnell
Rapid advancements in technology refine our understanding of intricate biological processes, but a crucial emphasis remains on understanding the assumptions and sources of uncertainty underlying biological measurements. This is particularly critical in cell signaling research, where a quantitative understanding of the fundamental mechanisms governing these transient events is essential for drug development, given their importance in both homeostatic and pathogenic processes. Western blotting, a technique developed decades ago, remains an indispensable tool for investigating cell signaling, protein expression, and protein-protein interactions. While improvements in statistical analysis and methodology reporting have undoubtedly enhanced data quality, understanding the underlying assumptions and limitations of visual inspection in Western blotting can provide valuable additional information for evaluating experimental conclusions. Using the example of agonist-induced receptor post-translational modification, we highlight the theoretical and experimental assumptions associated with Western blotting and demonstrate how raw blot data can offer clues to experimental variability that may not be fully captured by statistical analyses and reported methodologies. This article is not intended as a comprehensive technical review of Western blotting. Instead, we leverage an illustrative example to demonstrate how assumptions about experimental design and data normalization can be revealed within raw data and subsequently influence data interpretation.
技术的飞速发展完善了我们对错综复杂的生物过程的理解,但重点仍然是理解生物测量的假设和不确定性来源。这一点在细胞信号传导研究中尤为重要,鉴于瞬时事件在平衡和致病过程中的重要性,定量了解这些瞬时事件的基本机制对药物开发至关重要。几十年前开发的 Western 印迹技术仍然是研究细胞信号传导、蛋白质表达和蛋白质间相互作用不可或缺的工具。虽然统计分析和方法报告的改进无疑提高了数据质量,但了解 Western 印迹技术的基本假设和目视检查的局限性也能为评估实验结论提供有价值的额外信息。我们以激动剂诱导的受体翻译后修饰为例,强调了与 Western 印迹相关的理论和实验假设,并展示了原始印迹数据如何为统计分析和报告方法可能无法完全捕捉的实验变异性提供线索。本文无意作为一篇全面的 Western 印迹技术综述。相反,我们利用一个示例来说明实验设计和数据归一化的假设是如何在原始数据中显现出来并进而影响数据解读的。
{"title":"Seeing beyond the blot: A critical look at assumptions and raw data interpretation in Western blotting.","authors":"Maxwell S DeNies, Allen P Liu, Santiago Schnell","doi":"10.1515/bmc-2022-0047","DOIUrl":"10.1515/bmc-2022-0047","url":null,"abstract":"<p><p>Rapid advancements in technology refine our understanding of intricate biological processes, but a crucial emphasis remains on understanding the assumptions and sources of uncertainty underlying biological measurements. This is particularly critical in cell signaling research, where a quantitative understanding of the fundamental mechanisms governing these transient events is essential for drug development, given their importance in both homeostatic and pathogenic processes. Western blotting, a technique developed decades ago, remains an indispensable tool for investigating cell signaling, protein expression, and protein-protein interactions. While improvements in statistical analysis and methodology reporting have undoubtedly enhanced data quality, understanding the underlying assumptions and limitations of visual inspection in Western blotting can provide valuable additional information for evaluating experimental conclusions. Using the example of agonist-induced receptor post-translational modification, we highlight the theoretical and experimental assumptions associated with Western blotting and demonstrate how raw blot data can offer clues to experimental variability that may not be fully captured by statistical analyses and reported methodologies. This article is not intended as a comprehensive technical review of Western blotting. Instead, we leverage an illustrative example to demonstrate how assumptions about experimental design and data normalization can be revealed within raw data and subsequently influence data interpretation.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0046
Weronika Kruczkowska, Julia Gałęziewska, Mateusz Kciuk, Adrianna Gielecińska, Elżbieta Płuciennik, Zbigniew Pasieka, Lin-Yong Zhao, Yi-Jin Yu, Damian Kołat, Żaneta Kałuzińska-Kołat
Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.
{"title":"Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.","authors":"Weronika Kruczkowska, Julia Gałęziewska, Mateusz Kciuk, Adrianna Gielecińska, Elżbieta Płuciennik, Zbigniew Pasieka, Lin-Yong Zhao, Yi-Jin Yu, Damian Kołat, Żaneta Kałuzińska-Kołat","doi":"10.1515/bmc-2022-0046","DOIUrl":"10.1515/bmc-2022-0046","url":null,"abstract":"<p><p>Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-25eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0045
Mohd Shuaib, Smriti Chaudhri, Shashank Kumar
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. Due to the absence of obvious therapeutic targets, microRNAs (miRNAs) provide possible hope to treat TNBC. Withaferin A (WA), a steroidal lactone, possesses potential anticancer activity with lesser side effects. The present study identifies hub genes (CDKN3, TRAF6, CCND1, JAK1, MET, AXIN2, JAG1, VEGFA, BRCA1, E2F3, WNT1, CDK6, KRAS, MYB, MYCN, TGFβR2, NOTCH1, SIRT1, MYCN, NOTCH2, WNT3A) from the list of predicted targets of the differentially expressed miRNAs (DEMs) in WA-treated MDA-MB-231 cells using in silico protein-protein interaction network analysis. CCND1, CDK6, and TRAF6 hub genes were predicted as targets of miR-34a-5p and miR-146a-5p, respectively. The study found the lower expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells, and further, it was observed that WA treatment effectively restored the lost expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells. An anti-correlation expression pattern was found among the miR-34a-5p and miR-146a-5p and the respective target hub genes in WA-treated TNBC cells. In conclusion, WA might exert anti-cancer effect in TNBC cells by inducing miR-34a-5p and miR-146a-5p expressions and decreasing CCND1, CDK6, and TARF6 target hub genes in TNBC cells.
{"title":"Withaferin A alters the expression of microRNAs 146a-5p and 34a-5p and associated hub genes in MDA-MB-231 cells.","authors":"Mohd Shuaib, Smriti Chaudhri, Shashank Kumar","doi":"10.1515/bmc-2022-0045","DOIUrl":"10.1515/bmc-2022-0045","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. Due to the absence of obvious therapeutic targets, microRNAs (miRNAs) provide possible hope to treat TNBC. Withaferin A (WA), a steroidal lactone, possesses potential anticancer activity with lesser side effects. The present study identifies hub genes (<i>CDKN3</i>, <i>TRAF6</i>, <i>CCND1</i>, <i>JAK1</i>, <i>MET</i>, <i>AXIN2</i>, <i>JAG1</i>, <i>VEGFA</i>, <i>BRCA1</i>, <i>E2F3</i>, <i>WNT1</i>, <i>CDK6</i>, <i>KRAS</i>, <i>MYB</i>, <i>MYCN</i>, <i>TGFβR2</i>, <i>NOTCH1</i>, <i>SIRT1</i>, <i>MYCN</i>, <i>NOTCH2</i>, <i>WNT3A</i>) from the list of predicted targets of the differentially expressed miRNAs (DEMs) in WA-treated MDA-MB-231 cells using <i>in silico</i> protein-protein interaction network analysis. <i>CCND1</i>, <i>CDK6</i>, and <i>TRAF6</i> hub genes were predicted as targets of miR-34a-5p and miR-146a-5p, respectively. The study found the lower expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells, and further, it was observed that WA treatment effectively restored the lost expression of miR-34a-5p and miR-146a-5p in MDA-MB-231 cells. An anti-correlation expression pattern was found among the miR-34a-5p and miR-146a-5p and the respective target hub genes in WA-treated TNBC cells. In conclusion, WA might exert anti-cancer effect in TNBC cells by inducing miR-34a-5p and miR-146a-5p expressions and decreasing CCND1, CDK6, and TARF6 target hub genes in TNBC cells.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-19eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0044
Silvia Santillo, Luciano De Petrocellis, Carlo Musio
Opsins play a key role in the ability to sense light both in image-forming vision and in non-visual photoreception (NVP). These modalities, in most animal phyla, share the photoreceptor protein: an opsin-based protein binding a light-sensitive chromophore by a lysine (Lys) residue. So far, visual and non-visual opsins have been discovered throughout the Metazoa phyla, including the photoresponsive Hydra, an eyeless cnidarian considered the evolutionary sister species to bilaterians. To verify whether light influences and modulates opsin gene expression in Hydra, we utilized four expression sequence tags, similar to two classic opsins (SW rhodopsin and SW blue-sensitive opsin) and two non-visual opsins (melanopsin and peropsin), in investigating the expression patterns during both diurnal and circadian time, by means of a quantitative RT-PCR. The expression levels of all four genes fluctuated along the light hours of diurnal cycle with respect to the darkness one and, in constant dark condition of the circadian cycle, they increased. The monophasic behavior in the L12:D12 cycle turned into a triphasic expression profile during the continuous darkness condition. Consequently, while the diurnal opsin-like expression revealed a close dependence on light hours, the highest transcript levels were found in darkness, leading us to novel hypothesis that in Hydra, an "internal" biological rhythm autonomously supplies the opsins expression during the circadian time. In conclusion, in Hydra, both diurnal and circadian rhythms apparently regulate the expression of the so-called visual and non-visual opsins, as already demonstrated in higher invertebrate and vertebrate species. Our data confirm that Hydra is a suitable model for studying ancestral precursor of both visual and NVP, providing useful hints on the evolution of visual and photosensory systems.
{"title":"Diurnal and circadian regulation of opsin-like transcripts in the eyeless cnidarian <i>Hydra</i>.","authors":"Silvia Santillo, Luciano De Petrocellis, Carlo Musio","doi":"10.1515/bmc-2022-0044","DOIUrl":"https://doi.org/10.1515/bmc-2022-0044","url":null,"abstract":"<p><p>Opsins play a key role in the ability to sense light both in image-forming vision and in non-visual photoreception (NVP). These modalities, in most animal phyla, share the photoreceptor protein: an opsin-based protein binding a light-sensitive chromophore by a lysine (Lys) residue. So far, visual and non-visual opsins have been discovered throughout the Metazoa phyla, including the photoresponsive <i>Hydra</i>, an eyeless cnidarian considered the evolutionary sister species to bilaterians. To verify whether light influences and modulates opsin gene expression in <i>Hydra</i>, we utilized four expression sequence tags, similar to two classic opsins (SW rhodopsin and SW blue-sensitive opsin) and two non-visual opsins (melanopsin and peropsin), in investigating the expression patterns during both diurnal and circadian time, by means of a quantitative RT-PCR. The expression levels of all four genes fluctuated along the light hours of diurnal cycle with respect to the darkness one and, in constant dark condition of the circadian cycle, they increased. The monophasic behavior in the L12:D12 cycle turned into a triphasic expression profile during the continuous darkness condition. Consequently, while the diurnal opsin-like expression revealed a close dependence on light hours, the highest transcript levels were found in darkness, leading us to novel hypothesis that in <i>Hydra</i>, an \"internal\" biological rhythm autonomously supplies the opsins expression during the circadian time. In conclusion, in <i>Hydra</i>, both diurnal and circadian rhythms apparently regulate the expression of the so-called visual and non-visual opsins, as already demonstrated in higher invertebrate and vertebrate species. Our data confirm that <i>Hydra</i> is a suitable model for studying ancestral precursor of both visual and NVP, providing useful hints on the evolution of visual and photosensory systems.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-13eCollection Date: 2024-01-01DOI: 10.1515/bmc-2022-0043
Pravinkumar M Sonsare, Chellamuthu Gunavathi
Computational biology faces many challenges like protein secondary structure prediction (PSS), prediction of solvent accessibility, etc. In this work, we addressed PSS prediction. PSS is based on sequence-structure mapping and interaction among amino acid residues. We proposed an encoder-decoder with an attention mechanism model, which considers the mapping of sequence structure and interaction among residues. The attention mechanism is used to select prominent features from amino acid residues. The proposed model is trained on CB513 and CullPDB open datasets using the Nvidia DGX system. We have tested our proposed method for Q3 and Q8 accuracy, segment of overlap, and Mathew correlation coefficient. We achieved 70.63 and 78.93% Q3 and Q8 accuracy, respectively, on the CullPDB dataset whereas 79.8 and 77.13% Q3 and Q8 accuracy on the CB513 dataset. We observed improvement in SOV up to 80.29 and 91.3% on CullPDB and CB513 datasets. We achieved the results using our proposed model in very few epochs, which is better than the state-of-the-art methods.
{"title":"A novel approach for protein secondary structure prediction using encoder-decoder with attention mechanism model.","authors":"Pravinkumar M Sonsare, Chellamuthu Gunavathi","doi":"10.1515/bmc-2022-0043","DOIUrl":"10.1515/bmc-2022-0043","url":null,"abstract":"<p><p>Computational biology faces many challenges like protein secondary structure prediction (PSS), prediction of solvent accessibility, etc. In this work, we addressed PSS prediction. PSS is based on sequence-structure mapping and interaction among amino acid residues. We proposed an encoder-decoder with an attention mechanism model, which considers the mapping of sequence structure and interaction among residues. The attention mechanism is used to select prominent features from amino acid residues. The proposed model is trained on CB513 and CullPDB open datasets using the Nvidia DGX system. We have tested our proposed method for <i>Q</i> <sub>3</sub> and <i>Q</i> <sub>8</sub> accuracy, segment of overlap, and Mathew correlation coefficient. We achieved 70.63 and 78.93% <i>Q</i> <sub>3</sub> and <i>Q</i> <sub>8</sub> accuracy, respectively, on the CullPDB dataset whereas 79.8 and 77.13% <i>Q</i> <sub>3</sub> and <i>Q</i> <sub>8</sub> accuracy on the CB513 dataset. We observed improvement in SOV up to 80.29 and 91.3% on CullPDB and CB513 datasets. We achieved the results using our proposed model in very few epochs, which is better than the state-of-the-art methods.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}