{"title":"Metalloproteins and metalloproteomics in health and disease.","authors":"Iman Hassan Ibrahim","doi":"10.1016/bs.apcsb.2023.12.013","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.013","url":null,"abstract":"<p><p>Metalloproteins represents more than one third of human proteome, with huge variation in physiological functions and pathological implications, depending on the metal/metals involved and tissue context. Their functions range from catalysis, bioenergetics, redox, to DNA repair, cell proliferation, signaling, transport of vital elements, and immunity. The human metalloproteomic studies revealed that many families of metalloproteins along with individual metalloproteins are dysregulated under several clinical conditions. Also, several sorts of interaction between redox- active or redox- inert metalloproteins are observed in health and disease. Metalloproteins profiling shows distinct alterations in neurodegenerative diseases, cancer, inflammation, infection, diabetes mellitus, among other diseases. This makes metalloproteins -either individually or as families- a promising target for several therapeutic approaches. Inhibitors and activators of metalloenzymes, metal chelators, along with artificial metalloproteins could be versatile in diagnosis and treatment of several diseases, in addition to other biomedical and industrial applications.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"123-176"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Viral mimicry and endocrine system: Divulging the importance in host-microbial crosstalk.","authors":"Elora Kalita, Mamta Panda, Abhishek Rao, Rajan Kumar Pandey, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.03.005","DOIUrl":"10.1016/bs.apcsb.2024.03.005","url":null,"abstract":"<p><p>Host-pathogen interactions are complex associations which evolve over long co-evolutionary histories. Pathogens exhibit different mechanisms to gain advantage over their host. Mimicry of host factors is an influential tool in subverting host mechanisms to ensure pathogenesis. This chapter discusses such molecular mimicry exhibited during viral infections. Understanding the evolutionary relationships, shared identity and functional impact of the virus encoded mimics is critical. With a particular emphasis on viral mimics and their association with cancer and autoimmune diseases, this chapter highlights the importance of molecular mimicry in virus biology.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"421-436"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleonora Piscitelli, Iriczalli Cruz Maya, Cinzia Cocola, Valentina Martino, Edoardo Abeni, Paride Pelucchi, Elena Angeli, Patrizia Guida, Arianna Consiglio, Giorgio Grillo, Theodoros Karnavas, Angelos Gritzapis, Mira Palizban, Ioannis Missitzis, Martin Götte, Sabino Luini, James Kehler, Cristiana Balbino, Vincenzo Guarino, Luciano Milanesi, Ileana Zucchi, Alberto Diaspro, Rolland Reinbold
{"title":"Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.","authors":"Eleonora Piscitelli, Iriczalli Cruz Maya, Cinzia Cocola, Valentina Martino, Edoardo Abeni, Paride Pelucchi, Elena Angeli, Patrizia Guida, Arianna Consiglio, Giorgio Grillo, Theodoros Karnavas, Angelos Gritzapis, Mira Palizban, Ioannis Missitzis, Martin Götte, Sabino Luini, James Kehler, Cristiana Balbino, Vincenzo Guarino, Luciano Milanesi, Ileana Zucchi, Alberto Diaspro, Rolland Reinbold","doi":"10.1016/bs.apcsb.2024.03.008","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.03.008","url":null,"abstract":"<p><p>We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"331-360"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nachammai Kathiresan, Chandrabose Selvaraj, Sangavi Pandian, Gowtham Kumar Subbaraj, Abdulaziz S Alothaim, Sher Zaman Safi, Langeswaran Kulathaivel
{"title":"Proteomics and genomics insights on malignant osteosarcoma.","authors":"Nachammai Kathiresan, Chandrabose Selvaraj, Sangavi Pandian, Gowtham Kumar Subbaraj, Abdulaziz S Alothaim, Sher Zaman Safi, Langeswaran Kulathaivel","doi":"10.1016/bs.apcsb.2023.06.001","DOIUrl":"10.1016/bs.apcsb.2023.06.001","url":null,"abstract":"<p><p>Osteosarcoma is a malignant osseous neoplasm. Osteosarcoma is a primary bone malignancy capable of producing osteoid tissue or immature bones. A subsequent malignant degeneration of the primary bone pathology occurs less frequently in adults. The over-expression of several proteins, including Heat shock proteins, Cofilin, Annexins, Insulin-like growth factor, transforming growth factor-β, Receptor tyrosine kinase, Ezrin, Runx2, SATB2, ATF4, Annexins, cofilin, EGFR, VEGF, retinoblastoma 1 (Rb1) and secreted protein, has been associated to the development and progression of osteosarcoma. These proteins are involved in cell adhesion, migration, invasion, and the control of cell cycle and apoptosis. In genomic studies, osteosarcoma has been associated with several genetic abnormalities, including chromosomal rearrangements, gene mutations, and gene amplifications. These differentially expressed proteins could be used as early identification biomarkers or treatment targets. Proteomics and genomics play significant parts in enhancing our molecular understanding of osteosarcoma, and their integration provides essential insights into this aggressive bone cancer. This review will discuss the tumour biology that has assisted in helping us better understand the causes of osteosarcoma and how they could potentially be used to find new treatment targets and enhance the survival rate for osteosarcoma patients.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"138 ","pages":"275-300"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Technological advancements in viral vector designing and optimization for therapeutic applications.","authors":"Satyendra Singh, Anurag Kumar Pandey, Takhellambam Malemnganba, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2023.11.013","DOIUrl":"10.1016/bs.apcsb.2023.11.013","url":null,"abstract":"<p><p>Viral vector engineering is critical to the advancement of several sectors of biotechnology, gene therapy, and vaccine development. These vectors were produced from viruses, were employed to deliver therapeutic genes or to alter biological processes. The potential for viral vectors to improve the precision, safety, and efficiency of therapeutic interventions has boosted their demand. The dynamic interplay between technological advancements and computational tools in establishing the landscape of viral vector engineering and vector optimization for therapeutic reasons is discussed in this chapter. It also emphasizes the importance of in silico techniques in maximizing vector potential for therapeutics and many phases of viral vector engineering, from genomic analysis to computer modelling and advancements to improve precise gene delivery. High-throughput screening propels the expedited process of vector selection, and computational techniques to analyze complex omics data to further enhance vector capabilities have been discussed. As in silico models reveal insights into off-target effects and integration sites, vector safety (biodistribution and toxicity) remains a crucial part and bridges the gap between preclinical and clinical investigations. Despite the limitations, this chapter depicts a future in which technology and computing merge to catapult viral vector therapy into an era of boundless possibilities.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"57-87"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prasanna Kumar Selvam, Santhosh Mudipalli Elavarasu, T Dhanushkumar, Karthick Vasudevan, C George Priya Doss
{"title":"Exploring the role of estrogen and progestins in breast cancer: A genomic approach to diagnosis.","authors":"Prasanna Kumar Selvam, Santhosh Mudipalli Elavarasu, T Dhanushkumar, Karthick Vasudevan, C George Priya Doss","doi":"10.1016/bs.apcsb.2023.12.023","DOIUrl":"10.1016/bs.apcsb.2023.12.023","url":null,"abstract":"<p><p>Breast cancer (BC) is the most common cancer among women and a major cause of death from cancer. The role of estrogen and progestins, including synthetic hormones like R5020, in the development of BC has been highlighted in numerous studies. In our study, we employed machine learning and advanced bioinformatics to identify genes that could serve as diagnostic markers for BC. We thoroughly analyzed the transcriptomic data of two BC cell lines, T47D and UDC4, and performed differential gene expression analysis. We also conducted functional enrichment analysis to understand the biological functions influenced by these genes. Our study identified several diagnostic genes strongly associated with BC, including MIR6728, ENO1-IT1, ENO1-AS1, RNU6-304P, HMGN2P17, RP3-477M7.5, RP3-477M7.6, and CA6. The genes MIR6728, ENO1-IT1, ENO1-AS1, and HMGN2P17 are involved in cancer control, glycolysis, and DNA-related processes, while CA6 is associated with apoptosis and cancer development. These genes could potentially serve as predictors for BC, paving the way for more precise diagnostic methods and personalized treatment plans. This research enhances our understanding of BC and offers promising avenues for improving patient care in the future.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"25-43"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The biofilm proteome of Staphylococcus aureus and its implications for therapeutic interventions to biofilm-associated infections.","authors":"Dileep Francis, Gopika Veeramanickathadathil Hari, Abhijith Koonthanmala Subash, Anusha Bhairaddy, Atheene Joy","doi":"10.1016/bs.apcsb.2023.08.002","DOIUrl":"10.1016/bs.apcsb.2023.08.002","url":null,"abstract":"<p><p>Staphylococcus aureus is a major healthcare concern due to its ability to inflict life-threatening infections and evolve antibiotic resistance at an alarming pace. It is frequently associated with hospital-acquired infections, especially device-associated infections. Systemic infections due to S. aureus are difficult to treat and are associated with significant mortality and morbidity. The situation is worsened by the ability of S. aureus to form social associations called biofilms. Biofilms embed a community of cells with the ability to communicate with each other and share resources within a polysaccharide or protein matrix. S. aureus establish biofilms on tissues and conditioned abiotic surfaces. Biofilms are hyper-tolerant to antibiotics and help evade host immune responses. Biofilms exacerbate the severity and recalcitrance of device-associated infections. The development of a biofilm involves various biomolecules, such as polysaccharides, proteins and nucleic acids, contributing to different structural and functional roles. Interconnected signaling pathways and regulatory molecules modulate the expression of these molecules. A comprehensive understanding of the molecular biology of biofilm development would help to devise effective anti-biofilm therapeutics. Although bactericidal agents, antimicrobial peptides, bacteriophages and nano-conjugated anti-biofilm agents have been employed with varying levels of success, there is still a requirement for effective and clinically viable anti-biofilm therapeutics. Proteins that are expressed and utilized during biofilm formation, constituting the biofilm proteome, are a particularly attractive target for anti-biofilm strategies. The proteome can be explored to identify potential anti-biofilm drug targets and utilized for rational drug discovery. With the aim of uncovering the biofilm proteome, this chapter explores the mechanism of biofilm formation and its regulation. Furthermore, it explores the antibiofilm therapeutics targeted against the biofilm proteome.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"138 ","pages":"327-400"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harini Ravi, Soumik Das, V Devi Rajeswari, Ganesh Venkatraman, Abbas Alam Choudhury, Shreya Chakraborty, Gnanasambandan Ramanathan
{"title":"Hormonal regulation in diabetes: Special emphasis on sex hormones and metabolic traits.","authors":"Harini Ravi, Soumik Das, V Devi Rajeswari, Ganesh Venkatraman, Abbas Alam Choudhury, Shreya Chakraborty, Gnanasambandan Ramanathan","doi":"10.1016/bs.apcsb.2023.12.015","DOIUrl":"10.1016/bs.apcsb.2023.12.015","url":null,"abstract":"<p><p>Diabetes constitutes a significant global public health challenge that is rapidly reaching epidemic proportions. Among the non-communicable diseases, the incidence of diabetes is rising at an alarming rate. The International Diabetes Federation has documented a 9.09% prevalence of diabetes among individuals aged between 20 and 79 years. The interplay of gonadal hormones and gender differences is critical in regulating insulin sensitivity and glucose tolerance, and this dynamic is particularly crucial because of the escalating incidence of diabetes. Variations in insulin sensitivity are observed across genders, levels of adiposity, and age groups. Both estrogen and testosterone are seen to influence glucose metabolism and insulin sensitivity. This chapter surveys the present knowledge of sex differences, sex hormones, and chromosomes on insulin imbalance and diabetes development. It further highlights the influence of metabolic traits in diabetes and changes in sex hormones during diabetic pregnancy. Notably, even stressful lifestyles have been acknowledged to induce hormonal imbalances. Furthermore, it discusses the potential of hormonal therapy to help stabilize sex hormones in diabetic individuals and focuses on the most recent research investigating the correlation between sex hormones and diabetes.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"257-291"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Małgorzata Grzesiak, Monika Herian, Kinga Kamińska, Paula Ajersch
{"title":"Insight into vitamin D<sub>3</sub> action within the ovary-Basic and clinical aspects.","authors":"Małgorzata Grzesiak, Monika Herian, Kinga Kamińska, Paula Ajersch","doi":"10.1016/bs.apcsb.2024.04.003","DOIUrl":"10.1016/bs.apcsb.2024.04.003","url":null,"abstract":"<p><p>Vitamin D<sub>3</sub> is a fat-soluble secosteroid predominantly synthesized in the skin or delivered with a diet. Nevertheless, recently it is considered more as a hormone than a vitamin due to its pleiotropic function within the organism ensured by widely distributed vitamin D receptors and metabolic enzymes. Besides the main role in calcium and phosphorus homeostasis, vitamin D<sub>3</sub> was shown to regulate many cellular and metabolic processes in normal and cancerous tissues within the immune system, the cardiovascular system, the respiratory system and the endocrine system. The ovary is an important extraskeletal tissue of vitamin D<sub>3</sub> action and local metabolism, indicating its role in the regulation of ovarian functions upon physiological and pathological conditions. This chapter reviews firstly the updated information about vitamin D<sub>3</sub> metabolism and triggered intracellular pathways. Furthermore, the basic information about ovarian physiology and several aspects of vitamin D<sub>3</sub> effects within the ovary are presented. Finally, the special attention is paid into possible mechanism of vitamin D<sub>3</sub> action within ovarian pathologies such as premature ovarian failure, polycystic ovary syndrome, and ovarian cancer, considering its clinical application as alternative therapy.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"99-130"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thyroid hormone biosynthesis and its role in brain development and maintenance.","authors":"Janaina Sena de Souza","doi":"10.1016/bs.apcsb.2023.12.024","DOIUrl":"10.1016/bs.apcsb.2023.12.024","url":null,"abstract":"<p><p>Thyroid hormones are critical modulators in the physiological processes necessary to virtually all tissues, with exceptionally fundamental roles in brain development and maintenance. These hormones regulate essential neurodevelopment events, including neuronal migration, synaptogenesis, and myelination. Additionally, thyroid hormones are crucial for maintaining brain homeostasis and cognitive function in adulthood. This chapter aims to offer a comprehensive understanding of thyroid hormone biosynthesis and its intricate role in brain physiology. Here, we described the mechanisms underlying the biosynthesis of thyroid hormones, their influence on various aspects of brain development and ongoing maintenance, and the proteins in the brain that are responsive to these hormones. This chapter was geared towards broadening our understanding of thyroid hormone action in the brain, shedding light on potential therapeutic targets for neurodevelopmental and neurodegenerative disorders.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"329-365"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}