Article
Biochemistry & Molecular Biology
Mahamat Babagana, Lorin R. Brown, Hannah Z. Slabodkin, Julia V. Kichina, Eugene S. Kandel
Summary: Hyperactivity of AKT in cancer cells leads to increased sensitivity to proteotoxic stress, manifested by heightened response to heat shock and greater dependence on XBP1 for growth. This stress-induced vulnerability can be exploited for therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Veterinary Sciences
Samuel A. Atkin, Abu Saleh Md Moin, Stephen L. Atkin, Alexandra E. Butler
Summary: This study investigated the effects of hypoglycemia on the heat shock-related protein pathway. The results showed that hypoglycemia significantly decreased the expression of HSP90, 70, 27, and ubiquitin proteins, which are important for the protective response against heat stress.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Oncology
Sara Sannino, Allison M. Manuel, Chaowei Shang, Stacy G. Wendell, Peter Wipf, Jeffrey L. Brodsky
Summary: Proteostasis, the regulation of protein homeostasis, plays a role in controlling tumor growth and proliferation under proteotoxic stress conditions. Cancer cells rely more heavily on stress signaling and require the integrated stress response (ISR), amino acid metabolism, and efficient protein folding and degradation pathways to survive. This study explores the influence of amino acid abundance on cell survival when Hsp70, a key regulator of proteostasis, is inhibited. The findings suggest that amino acid availability reconfigures the proteostasis network and amino acid supplementation, particularly arginine addition, can trigger cancer cell death by blocking autophagy.
MOLECULAR CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Fereshteh Radmanesh, Mazdak Razi, Ali Shalizar-Jalali
Summary: The study revealed that curcumin nano-micelle (NCMN) has an impact on testicular antioxidant status, leading to increased expression of heat shock proteins (Hsp) 70-2a and Hsp90, as well as cell DNA and mRNA damage, reduced sperm count, motility, and DNA integrity.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yu-Ning Lu, Sarah Kavianpour, Tao Zhang, Xumei Zhang, Dao Nguyen, Ravi Thombre, Lu He, Jiou Wang
Summary: This study identifies MARK2 as a direct kinase of eIF2α in response to proteotoxic stress, and MARK2 itself is regulated by PKCδ. Both MARK2 and PKCδ are activated via phosphorylation in cellular proteotoxic stress responses and human diseases, suggesting a critical role in these processes.
Article
Oncology
Yasuhisa Murai, Ukhyun Jo, Junko Murai, Lisa M. Jenkins, Shar-Yin N. Huang, Sirisha Chakka, Lu Chen, Ken Cheng, Shinsaku Fukuda, Naoko Takebe, Yves Pommier
Summary: The study reveals that SLFN11 deficiency induces proteotoxic stress and sensitizes cancer cells to TAK-243, suggesting that profiling SLFN11 status can serve as a therapeutic biomarker for cancer therapy.
Review
Biochemistry & Molecular Biology
Akanksha Verma, S. Sumi, Mahendra Seervi
Summary: Heat shock proteins (HSPs) play crucial roles in cell survival by interacting with apoptosis signaling components, maintaining protein homeostasis, and regulating the assembly and disassembly of stress granules (SGs) in the cytoplasm, which are important for cell survival under stressful conditions. Their intricate molecular signaling in and around the nexus of HSPs-SGs is essential in managing chronic diseases like cancer and neurodegenerative diseases.
Article
Cell Biology
Rajasri Sarkar, Kannan Boosi Narayana Rao, Mainak Pratim Jha, Koyeli Mapa
Summary: Mitochondria and endoplasmic reticulum (ER) maintain close contact to ensure their functions, and intact ER-unfolded protein response (UPR) pathway plays an important role in tolerating proteotoxic stress in mitochondrial intermembrane space (IMS). Localized proteotoxic stress within IMS does not induce ER-UPR, but its artificial activation enhances cell resistance. Overexpression of components in ER-mitochondria contact sites is beneficial for general mitochondrial proteotoxic stress.
CELL STRESS & CHAPERONES
(2022)
Article
Biochemistry & Molecular Biology
Kannan Boosi Narayana Rao, Pratima Pandey, Rajasri Sarkar, Asmita Ghosh, Shemin Mansuri, Mudassar Ali, Priyanka Majumder, K. Ranjith Kumar, Arjun Ray, Swasti Raychaudhuri, Koyeli Mapa
Summary: The study reveals the differences in stress response between mitochondrial matrix and inter-membrane space (IMS) by specifically targeting stressor proteins to these sub-mitochondrial compartments. It is found that mitochondrial proteotoxicity leads to growth arrest and fragmentation of yeast cells, and an adaptive suppression of mitochondrial respiration with upregulation of glycolysis. Transcriptomics and proteomics analysis further show that stressor proteins targeted to IMS specifically upregulate IMS-chaperones and TOM complex components, while stressor proteins targeted to matrix upregulate matrix-chaperones and cytosolic PQC components. Genetic interaction study indicates the modulatory role of TOM complex components in IMS-stress response and VMS1 in matrix stress response.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
Bothina Mohammed Alharbi, Tahani H. Albinhassan, Razan Ali Alzahrani, Abderrezak Bouchama, Sameer Mohammad, Awatif Abdulaziz Alomari, May Nasser Bin-Jumah, Entissar S. AlSuhaibani, Shuja Shafi Malik
Summary: Rising temperatures and heat waves caused by climate change are detrimental to human health. Exposure to extreme heat during heat waves can cause heat-related illnesses, including heat stroke, which can result in permanent disability. Heat can damage proteins, leading to their misfolding and aggregation, which can be neurotoxic and contribute to neurodegenerative disorders.
Article
Multidisciplinary Sciences
Siu Hong Dexter Wong, Bohan Yin, Zhuo Li, Weihao Yuan, Qin Zhang, Xian Xie, Youhua Tan, Nathalie Wong, Kunyu Zhang, Liming Bian
Summary: Biophysical cues of a rigid tumor matrix play a crucial role in promoting cancer cell malignancy. Our study demonstrates that when cancer cells are grown in stiff hydrogels, which expose them to significant confining stress, they exhibit enhanced growth and activation of specific signaling pathways related to stemness. This phenomenon is mediated by the heat shock protein (Hsp) and its downstream signaling molecules, and can be suppressed by culturing the cells in softer hydrogels or relieving the stress in stiff hydrogels. Mechanopriming of cancer cells through three-dimensional culture enhances their tumorigenicity and metastatic potential in animal models, while inhibiting Hsp70 improves the effectiveness of chemotherapy. This study highlights the critical role of Hsp70 in regulating cancer cell malignancy under mechanically stressed conditions and its potential as a therapeutic target.
Article
Plant Sciences
Alfonso Munoz, Silvina Mangano, Rene Toribio, Lourdes Fernandez-Calvino, Juan C. del Pozo, M. Mar Castellano
Summary: This study reveals the role of HOP family in plant development and its involvement in auxin signaling. HOP proteins interact and stabilize TIR1, a key component in auxin signal transduction, leading to reduced auxin sensitivity in the hop1 hop2 hop3 triple mutant. Additionally, HOP and SGT1b, another co-chaperone, synergistically cooperate in stabilizing common targets involved in plant development.
PLANT CELL AND ENVIRONMENT
(2022)
Article
Biochemistry & Molecular Biology
Juncheng Wei, Bryan T. Harada, Dan Lu, Ruihua Ma, Beixue Gao, Yanan Xu, Elena Montauti, Nikita Mani, Shuvam M. Chaudhuri, Shana Gregory, Samuel E. Weinberg, Donna D. Zhang, Richard Green, Chuan He, Deyu Fang
Summary: The study reveals that accumulation of unfolded/misfolded proteins selectively induces N-6-adenosine-methyltransferase-14 (METTL14) expression, which promotes C/EBP-homologous protein (CHOP) mRNA decay to inhibit pro-apoptotic gene expression. The unfolded protein response induces METTL14 expression by competing against the ER-associated degradation machinery, resulting in adaptation to proteotoxic stress.
Review
Biochemistry & Molecular Biology
Giusi Alberti, Giuseppe Vergilio, Letizia Paladino, Rosario Barone, Francesco Cappello, Everly Conway de Macario, Alberto J. L. Macario, Fabio Bucchieri, Francesca Rappa
Summary: Breast cancer is a major public health problem, and the role of the chaperone system in its development and treatment is still poorly understood. This article discusses the pro-carcinogenic roles of four chaperones, Hsp27, Hsp60, Hsp70, and Hsp90, in breast cancer and their potential for anti-cancer therapies. The article also briefly explores the potential of extracellular vesicles in breast cancer diagnosis and management. Overall, understanding the chaperone system can provide new insights into the mechanisms of breast cancer and the development of targeted treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Paul Langton, Michael P. Baumgartner, Remi Logeay, Eugenia P. Piddini
Summary: This study reveals the relationship between protein aggregates and Xrp1 and Irbp18 in cell competition. Xrp1 and Irbp18 promote protein aggregate formation, while protein aggregates induce the activity of Xrp1 and Irbp18. This amplifies stress signaling, reduces cell fitness, and leads to the elimination of cells.
Review
Endocrinology & Metabolism
Mohsen Khosravi-Maharlooei, Rachel Madley, Chiara Borsotti, Leonardo M. R. Ferreira, Robert C. Sharp, Michael A. Brehm, Dale L. Greiner, Audrey V. Parent, Mark S. Anderson, Megan Sykes, Remi J. Creusot
Summary: This review summarizes the insights provided by animal models of type 1 diabetes in understanding the role and regulation of the immune system in human disease pathogenesis. The article describes the various models developed so far and discusses their limitations and the need for improved physiological relevance.
MOLECULAR METABOLISM
(2022)
Article
Medicine, General & Internal
Teresa Cunha-Oliveira, Daniela Franco Silva, Luis Segura, Ines Baldeiras, Ricardo Marques, Tatiana Rosenstock, Paulo J. Oliveira, Filomena S. G. Silva
Summary: Distinct redox signatures were found in lymphoblasts from mutSOD1, undSOD1, and healthy controls, which can serve as therapeutic targets for ALS drug development. High heterogeneity in redox profiles between cohorts was observed, but clustering analysis successfully segregated healthy controls from ALS samples based on specific parameters. These findings provide valuable insights for understanding oxidative stress profiles in different forms of ALS and potential treatment strategies.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Sonia A. Pinho, Claudio F. Costa, Claudia M. Deus, Sonia L. C. Pinho, Ines Miranda-Santos, Goncalo Afonso, Olivia Bagshaw, Jeffrey A. Stuart, Paulo J. Oliveira, Teresa Cunha-Oliveira
Summary: Cell culture conditions have a significant impact on cell metabolism. This study demonstrates that using a cell culture medium that induces oxidative phosphorylation (OXPHOSm) allows for the selective inhibition of mitochondrial adenosine triphosphate (ATP) production in normal human dermal fibroblasts (NHDF), providing an ideal model to study mitochondrial health and stress.
Article
Biochemistry & Molecular Biology
Rui F. Simoes, Paulo J. Oliveira, Teresa Cunha-Oliveira, Francisco B. Pereira
Summary: The prevalence of neurodegenerative diseases is increasing with aging population, but diagnostics and therapeutics have not seen significant improvements. Studying and modulating mitochondrial alterations offer promising strategies for predicting and preventing neurotoxicity and neuronal cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Teresa Cunha-Oliveira, Marcelo Carvalho, Vilma Sardao, Elisabete Ferreiro, Debora Mena, Francisco B. Pereira, Fernanda Borges, Paulo J. Oliveira, Filomena S. G. Silva
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with mitochondrial alterations in lymphoblasts that may have diagnostic and therapeutic implications.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Cell Biology
Emiliano Panieri, Sonia A. Pinho, Goncalo J. M. Afonso, Paulo J. Oliveira, Teresa Cunha-Oliveira, Luciano Saso
Summary: The NRF2-KEAP1 system regulates a wide range of transcriptional targets involved in redox homeostasis and cellular protection. NRF2 is a key driver of tumor progression and treatment resistance in cancer cells, making it a promising therapeutic target. Additionally, NRF2 has functional crosstalk with mitochondria, influencing mitochondrial homeostasis and cancer cell biology.
Review
Immunology
Nikolaos Skartsis, Yannick D. Muller, Leonardo M. R. Ferreira
Summary: Novel biologics currently being tested in clinical trials aim to provide highly efficient immunosuppression with minimal side effects by targeting specific inflammatory mediators involved in immune system dysregulation. However, the pleiotropic nature of these mediators and the potential for cell-to-cell interactions can lead to unpredictable results. Mechanistic understanding of immune mediators is necessary for predicting responses to biologic drugs.
CLINICAL IMMUNOLOGY
(2023)
Review
Immunology
Farbod Ghobadinezhad, Nasim Ebrahimi, Fatemeh Mozaffari, Neda Moradi, Sheida Beiranvand, Mehran Pournazari, Fatemeh Rezaei-Tazangi, Roya Khorram, Maral Afshinpour, Rob A. Robino, Amir Reza Aref, Leonardo M. R. Ferreira
Summary: Autoimmune diseases are characterized by unwanted immune responses to self-antigens, leading to immune responses against self-tissues. Regulatory immune cells, such as T cells, B cells, dendritic cells, and myeloid suppressor cells, play important roles in maintaining immune homeostasis and in the development of autoimmune diseases. Targeting or engineering these cells shows promise as a therapeutic approach for different autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Nikolaos Skartsis, Leonardo M. R. Ferreira, Qizhi Tang
Summary: TNFa blocking agents, the first-in-class biologic drugs used for treating autoimmune diseases, have shown paradoxical exacerbation of autoimmunity in some patients. The complex signaling pathways of TNFa might explain the controversial findings of previous studies. Targeted manipulation of TNFa-TNF receptor signaling on select CD4(+) T cell subsets may offer specific therapeutic interventions for autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Antonio Jorge Guiomar, Ana M. Urbano
Summary: The prevalence of chronic, non-healing skin wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers, is increasing due to the aging population, obesity, and diabetes. These wounds often become infected, leading to life-threatening complications and significant socioeconomic burden. Antimicrobial dressings incorporating polyhexanide (PHMB) have been introduced, but none have shown comprehensive antimicrobial activity. This review summarizes studies on PHMB-releasing membranes (PRMs) for wound dressings, including preparation, physical properties, drug loading and release, antibacterial activity, biocompatibility, wound-healing capacity, and clinical trials.
Article
Cell & Tissue Engineering
Leonardo M. R. Ferreira
Summary: The Advanced Therapies Week 2023 conference held in Miami showcased the future of cell therapy through discussions on allogeneic and autologous cell therapies, cell manufacture automation, gene therapy for autoimmune diseases, and more. The conference predicted that the US FDA will approve several cell and gene therapies in the coming decade, along with the development of new manufacturing devices.
REGENERATIVE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Sonia A. Pinho, Sandra I. Anjo, Teresa Cunha-Oliveira
Summary: Theragnostics is a promising strategy that combines diagnostics and therapeutics in a personalized manner. This review emphasizes the significance of redox homeostasis and mitochondrial function in personalized theragnostics. Disruption of redox homeostasis can lead to oxidative stress and cellular damage, which are associated with various diseases. Developing models of oxidative stress and mitochondrial dysfunction in metabolically conditioned cells allows for studying disease mechanisms and developing new therapies. By selecting appropriate cellular models, optimizing cell culture conditions, and validating the models, it is possible to identify the most promising therapeutic options and tailor treatments to individual patients. Overall, this review highlights the importance of precise and individualized approaches in theragnostics and the need for accurate in vitro models reflecting in vivo conditions.
Review
Chemistry, Inorganic & Nuclear
Krishnakumar Balu, Selvam Kaliyamoorthy, Mani Durai, Antonio Aguiar, Margarida C. M. Sobral, I. Muthuvel, Sakthivel Kumaravel, Balakrishna Avula, Abilio J. F. N. Sobral, Young-Ho Ahn
Summary: Materials based on semiconducting oxides are widely used in catalysis, photocatalysis, and other fields. Zinc oxide (ZnO), with its catalytic and optoelectronic capabilities, is utilized in various industries. Porphyrins, biomimetic molecules, can be modified to synthesize derivatives with remarkable optoelectronic properties. The combination of porphyrins and ZnO can lead to the development of hybrid materials with enhanced optical, electronic, and chemical properties. This review aims to present the evolution of ZnO/porphyrin hybrids and future research trends in this field.
INORGANIC CHEMISTRY COMMUNICATIONS
(2023)
Meeting Abstract
Medicine, General & Internal
M. Sobral, A. M. Urbano, A. S. Mata, I. C. Rosa, P. L. Abreu
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Medicine, General & Internal
A. Mata, I. C. Rosa, M. C. Sobral, A. M. Urbano
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)