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Articles 1 - 20 of 20
Full-Text Articles in Medicine and Health Sciences
Real Time Monitoring Of Children, And Adults With Mental Disabilities Using A Low-Cost Non-Invasive Electronic Device, Carlos Polanco, Ignacio Islas Vazquez, Adrian Martinez-Rivas, Miguel Arias-Estrada, Thomas Buhse, Juan J. Calva, Carlos Aguilar Salinas, Claudia Pimentel Instituto Nacional De Pediatría, Vladimir N. Uversky
Real Time Monitoring Of Children, And Adults With Mental Disabilities Using A Low-Cost Non-Invasive Electronic Device, Carlos Polanco, Ignacio Islas Vazquez, Adrian Martinez-Rivas, Miguel Arias-Estrada, Thomas Buhse, Juan J. Calva, Carlos Aguilar Salinas, Claudia Pimentel Instituto Nacional De Pediatría, Vladimir N. Uversky
Molecular Medicine Faculty Publications
There are a growing number of small children—as well as adults—with mental disabilities (including elderly citizens with Alzheimer’s disease or other forms of age-related dementia) that are getting lost in rural and urban areas for various reasons. Establishing their location within the first 72 h is crucial because lost people are exposed to all kinds of adverse conditions and in the case of the elderly, this is further aggravated if prescribed medication is needed. Herein we describe a non-invasive, low-cost electronic device that operates constantly, keeping track of time, the geographical location and the identification of the subject using it. …
Identification And Initial Characterization Of The Effectors Of An Anther Smut Fungus And Potential Host Target Proteins, Venkata S. Kuppireddy, Vladimir N. Uversky, Su San Toh, Ming-Chang Tsai, William C. Beckerson, Catarina Cahill, Brittany Carman, Michael H. Perlin
Identification And Initial Characterization Of The Effectors Of An Anther Smut Fungus And Potential Host Target Proteins, Venkata S. Kuppireddy, Vladimir N. Uversky, Su San Toh, Ming-Chang Tsai, William C. Beckerson, Catarina Cahill, Brittany Carman, Michael H. Perlin
Molecular Medicine Faculty Publications
(1) Background: Plant pathogenic fungi often display high levels of host specificity and biotrophic fungi; in particular, they must manipulate their hosts to avoid detection and to complete their obligate pathogenic lifecycles. One important strategy of such fungi is the secretion of small proteins that serve as effectors in this process. Microbotryum violaceum is a species complex whose members infect members of the Caryophyllaceae; M. lychnidis-dioicae, a parasite on Silene latifolia, is one of the best studied interactions. We are interested in identifying and characterizing effectors of the fungus and possible corresponding host targets; (2) Methods: In silico analysis of …
Structure And Conformational Properties Of D-Glucose/D-Galactose-Binding Protein In Crowded Milieu, Alexander V. Fonin, Sergey A. Silonov, Asiia K. Sitdikova, Irina M. Kuznetsova, Vladimir N. Uversky
Structure And Conformational Properties Of D-Glucose/D-Galactose-Binding Protein In Crowded Milieu, Alexander V. Fonin, Sergey A. Silonov, Asiia K. Sitdikova, Irina M. Kuznetsova, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders. For example, in comparison with the GGBP in buffer, the intrinsic fluorescence spectrum of this protein was shifted to …
A Comprehensive Survey Of The Roles Of Highly Disordered Proteins In Type 2 Diabetes, Zhihua Du, Vladimir N. Uversky
A Comprehensive Survey Of The Roles Of Highly Disordered Proteins In Type 2 Diabetes, Zhihua Du, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis. It is known that many proteins associated with different human maladies are intrinsically disordered as a whole, or contain intrinsically disordered regions. The presented study shows …
Toxoplasma Gondii Ap2ix-4 Regulates Gene Expression During Bradyzoite Development, Sherri Huang, Michael J. Holmes, Joshua B. Radke, Dong-Pyo Hong, Ting-Kai Liu, Michael W. White, William J. Sullivan Jr.
Toxoplasma Gondii Ap2ix-4 Regulates Gene Expression During Bradyzoite Development, Sherri Huang, Michael J. Holmes, Joshua B. Radke, Dong-Pyo Hong, Ting-Kai Liu, Michael W. White, William J. Sullivan Jr.
Molecular Medicine Faculty Publications
Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. …
Photophysical Properties Of Fluorescent Probe Thioflavin T In Crowded Milieu, Natalia P. Rodina, Maksim I. Sulatsky, Anna I. Sulatskaya, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov
Photophysical Properties Of Fluorescent Probe Thioflavin T In Crowded Milieu, Natalia P. Rodina, Maksim I. Sulatsky, Anna I. Sulatskaya, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov
Molecular Medicine Faculty Publications
Thioflavin T (ThT) is a widely used fluorescent probe of amyloid fibrils, which accompanies many serious neurodegenerative and other diseases. Until recently, examinations of processes of amyloid fibril formation in vitro were conducted in solutions whose properties were significantly different from those found inside the densely packed cells. Such crowded cellular milieu is typically simulated in vitro using concentrated solutions of inert polymers, which do not usually interact with proteins. However, these crowding agents can have a direct effect on the ThT molecule, and this effect must be taken into account. We examined the influence of PEG-400, PEG-12000, and Dextran-70 …
Diagnostic And Prognostic Relevance Of Cp2c And Yy1 Expression In Hepatocellular Carcinoma, Ji Sook Kim, Seung Han Son, Min Young Kim, Dongho Choi, Ik-Soon Jang, Seung Sam Paik, Ji Hyung Chae, Vladimir N. Uversky, Chul Geun Kim
Diagnostic And Prognostic Relevance Of Cp2c And Yy1 Expression In Hepatocellular Carcinoma, Ji Sook Kim, Seung Han Son, Min Young Kim, Dongho Choi, Ik-Soon Jang, Seung Sam Paik, Ji Hyung Chae, Vladimir N. Uversky, Chul Geun Kim
Molecular Medicine Faculty Publications
Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a …
Carbonyl-Based Blue Autofluorescence Of Proteins And Amino Acids, Chamani Niyangoda, Tatiana Miti, Leonid Breydo, Vladimir Uversky, Martin Muschol
Carbonyl-Based Blue Autofluorescence Of Proteins And Amino Acids, Chamani Niyangoda, Tatiana Miti, Leonid Breydo, Vladimir Uversky, Martin Muschol
Molecular Medicine Faculty Publications
Intrinsic protein fluorescence is inextricably linked to the near-UV autofluorescence of aromatic amino acids. Here we show that a novel deep-blue autofluorescence (dbAF), previously thought to emerge as a result of protein aggregation, is present at the level of monomeric proteins and even poly- and single amino acids. Just as its aggregation-related counterpart, this autofluorescence does not depend on aromatic residues, can be excited at the long wavelength edge of the UV and emits in the deep blue. Differences in dbAF excitation and emission peaks and intensities from proteins and single amino acids upon changes in solution conditions suggest dbAF’s …
The Relationship Between Folding And Activity In Ureg, An Intrinsically Disordered Enzyme, Marta Palombo, Alessio Bonucci, Emilien Etienne, Stefano Ciurli, Vladimir N. Uversky, Bruno Guigliarelli, Valérie Belle, Elisabetta Mileo, Barbara Zambelli
The Relationship Between Folding And Activity In Ureg, An Intrinsically Disordered Enzyme, Marta Palombo, Alessio Bonucci, Emilien Etienne, Stefano Ciurli, Vladimir N. Uversky, Bruno Guigliarelli, Valérie Belle, Elisabetta Mileo, Barbara Zambelli
Molecular Medicine Faculty Publications
A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease. The effect of …
Looking At The Recent Advances In Understanding Α-Synuclein And Its Aggregation Through The Proteoform Prism, Vladimir N. Uversky
Looking At The Recent Advances In Understanding Α-Synuclein And Its Aggregation Through The Proteoform Prism, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Despite attracting the close attention of multiple researchers for the past 25 years, α-synuclein continues to be an enigma, hiding sacred truth related to its structure, function, and dysfunction, concealing mechanisms of its pathological spread within the affected brain during disease progression, and, above all, covering up the molecular mechanisms of its multipathogenicity, i.e. the ability to be associated with the pathogenesis of various diseases. The goal of this article is to present the most recent advances in understanding of this protein and its aggregation and to show that the remarkable structural, functional, and dysfunctional multifaceted nature of α-synuclein can …
Disprot 7.0: A Major Update Of The Database Of Disordered Proteins, Damiano Piovesan, Francesco Tabaro, Ivan Mičetić, Marco Necci, Federica Quaglia, Christopher J. Oldfield, Maria Cristina Aspromonte, Norman E. Davey, Radoslav Davidović, Zsuzsanna Dosztányi, Arne Elofsson, Alessandra Gasparini, András Hatos, Andrey V. Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B. Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D. Tsirigos, Nevena Veljković, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N. Uversky, A. Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C.E. Tosatto
Disprot 7.0: A Major Update Of The Database Of Disordered Proteins, Damiano Piovesan, Francesco Tabaro, Ivan Mičetić, Marco Necci, Federica Quaglia, Christopher J. Oldfield, Maria Cristina Aspromonte, Norman E. Davey, Radoslav Davidović, Zsuzsanna Dosztányi, Arne Elofsson, Alessandra Gasparini, András Hatos, Andrey V. Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B. Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D. Tsirigos, Nevena Veljković, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N. Uversky, A. Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C.E. Tosatto
Molecular Medicine Faculty Publications
The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as …
Data On Evolution Of Intrinsically Disordered Regions Of The Human Kinome And Contribution Of Fak1 Idrs To Cytoskeletal Remodeling, Jaymin J. Kathiriya, Ravi Ramesh Pathak, Alexandr Bezginov, Bin Xue, Vladimir N. Uversky, Elisabeth R.M. Tillier, Vrushank Davé
Data On Evolution Of Intrinsically Disordered Regions Of The Human Kinome And Contribution Of Fak1 Idrs To Cytoskeletal Remodeling, Jaymin J. Kathiriya, Ravi Ramesh Pathak, Alexandr Bezginov, Bin Xue, Vladimir N. Uversky, Elisabeth R.M. Tillier, Vrushank Davé
Molecular Medicine Faculty Publications
We present data on the evolution of intrinsically disordered regions (IDRs) taking into account the entire human protein kinome. The evolutionary data of the IDRs with respect to the kinase domains (KDs) and kinases as a whole protein (WP) are reported. Further, we have reported its post translational modifications of FAK1 IDRs and their contribution to the cytoskeletal remodeling. We also report the data to build a protein-protein interaction (PPI) network of primary and secondary FAK1-interacting hybrid proteins. Detailed analysis of the data and its effect on FAK1-related functions have been described in “Structural pliability adjacent to the kinase domain …
Electronegativity And Intrinsic Disorder Of Preeclampsia-Related Proteins, Carlos Polanco, Jorge Alberto Castañón-González, Vladimir N. Uversky, Thomas Buhse, José Lino Mendoza, Juan J. Calva
Electronegativity And Intrinsic Disorder Of Preeclampsia-Related Proteins, Carlos Polanco, Jorge Alberto Castañón-González, Vladimir N. Uversky, Thomas Buhse, José Lino Mendoza, Juan J. Calva
Molecular Medicine Faculty Publications
Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study in which evaluated the commonness and potential functionality of intrinsic disorder in these proteins and also made an attempt to characterize their origin. To this end, we used a several supervised techniques, as a Polarity Index Method (PIM), which evaluates the electronegativity of proteins from their sequence alone. Peculiarities of resulting polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, …
Mhc Class Ii Associated Stomach Cancer Mutations Correlate With Lack Of Subsequent Tumor Development, John M. Yavorski, George Blanck
Mhc Class Ii Associated Stomach Cancer Mutations Correlate With Lack Of Subsequent Tumor Development, John M. Yavorski, George Blanck
Molecular Medicine Faculty Publications
The role of tumor cell expression of major histocompatibility class II (MHCII) has been controversial, with evidence indicating that tumor cell expression of MHCII may lead to an anti‑tumor immune response and to tumor cell apoptosis and that MHCII has pro‑tumorigenic functions. The cancer genome atlas (TCGA) indicates numerous deleterious mutations for the highly specific, MHCII transcriptional activation proteins, RFX5, RFXAP, RFXANK and CIITA. Also, mutations in the non‑polymorphic, human leukocyte antigen (HLA)‑DRA gene, which encodes the heavy chain for the most prominent human MHCII molecule, HLA‑DR, are common. For many, if not most TCGA cancer datasets, the MHCII specific …
Calreticulin: Challenges Posed By The Intrinsically Disordered Nature Of Calreticulin To The Study Of Its Function, Lilian Varricchio, Mario Falchi, Massimiliano Dall'ora, Benedittis, Caterina De Benedittis, Alessandra Ruggeri, Vladimir N. Uversky, Anna Rita Migliaccio
Calreticulin: Challenges Posed By The Intrinsically Disordered Nature Of Calreticulin To The Study Of Its Function, Lilian Varricchio, Mario Falchi, Massimiliano Dall'ora, Benedittis, Caterina De Benedittis, Alessandra Ruggeri, Vladimir N. Uversky, Anna Rita Migliaccio
Molecular Medicine Faculty Publications
Calreticulin is a Ca2+-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca2+, calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need …
Functional Analysis Of Human Hub Proteins And Their Interactors Involved In The Intrinsic Disorder-Enriched Interactions, Gang Hu, Zhonghua Wu, Vladimir N. Uversky, Lukasz Kurgan
Functional Analysis Of Human Hub Proteins And Their Interactors Involved In The Intrinsic Disorder-Enriched Interactions, Gang Hu, Zhonghua Wu, Vladimir N. Uversky, Lukasz Kurgan
Molecular Medicine Faculty Publications
Some of the intrinsically disordered proteins and protein regions are promiscuous interactors that are involved in one-to-many and many-to-one binding. Several studies have analyzed enrichment of intrinsic disorder among the promiscuous hub proteins. We extended these works by providing a detailed functional characterization of the disorder-enriched hub protein-protein interactions (PPIs), including both hubs and their interactors, and by analyzing their enrichment among disease-associated proteins. We focused on the human interactome, given its high degree of completeness and relevance to the analysis of the disease-linked proteins. We quantified and investigated numerous functional and structural characteristics of the disorder-enriched hub PPIs, including …
Human Cyclophilin 40 Unravels Neurotoxic Amyloids, Jeremy D. Baker, Lindsey B. Shelton, Dali Zheng, Filippo Favretto, Bryce A. Nordhues, April Darling, Leia E. Sullivan, Zheying Sun, Parth K. Solanki, Mackenzie D. Martin, Amirthaa Suntharalingam, Jonathan J. Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N. Uversky, Markus Zweckstetter, Chad A. Dickey, John Koren Iii, Laura J. Blair
Human Cyclophilin 40 Unravels Neurotoxic Amyloids, Jeremy D. Baker, Lindsey B. Shelton, Dali Zheng, Filippo Favretto, Bryce A. Nordhues, April Darling, Leia E. Sullivan, Zheying Sun, Parth K. Solanki, Mackenzie D. Martin, Amirthaa Suntharalingam, Jonathan J. Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N. Uversky, Markus Zweckstetter, Chad A. Dickey, John Koren Iii, Laura J. Blair
Molecular Medicine Faculty Publications
The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer’s disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases). Here we show that cyclophilin 40 (CyP40), a PPIase, dissolves tau amyloids in vitro. Additionally, CyP40 ameliorated silver-positive and oligomeric tau species in a mouse model …
Intrinsic Disorder In Proteins With Pathogenic Repeat Expansions, April L. Darling, Vladimir N. Uversky
Intrinsic Disorder In Proteins With Pathogenic Repeat Expansions, April L. Darling, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Intrinsically disordered proteins and proteins with intrinsically disordered regions have been shown to be highly prevalent in disease. Furthermore, disease-causing expansions of the regions containing tandem amino acid repeats often push repetitive proteins towards formation of irreversible aggregates. In fact, in disease-relevant proteins, the increased repeat length often positively correlates with the increased aggregation efficiency and the increased disease severity and penetrance, being negatively correlated with the age of disease onset. The major categories of repeat extensions involved in disease include poly-glutamine and poly-alanine homorepeats, which are often times located in the intrinsically disordered regions, as well as repeats in …
Osmolyte-Like Stabilizing Effects Of Low Gdnhcl Concentrations On D-Glucose/D-Galactose-Binding Protein, Alexander V. Fonin, Alexandra D. Golikova, Irina A. Zvereva, Sabato D’Auria, Maria Staiano, Vladimir N. Uversky, Irina M. Kuznetsova, Konstantin K. Turoverov
Osmolyte-Like Stabilizing Effects Of Low Gdnhcl Concentrations On D-Glucose/D-Galactose-Binding Protein, Alexander V. Fonin, Alexandra D. Golikova, Irina A. Zvereva, Sabato D’Auria, Maria Staiano, Vladimir N. Uversky, Irina M. Kuznetsova, Konstantin K. Turoverov
Molecular Medicine Faculty Publications
The ability of d-glucose/d-galactose-binding protein (GGBP) to reversibly interact with its ligands, glucose and galactose, makes this protein an attractive candidate for sensing elements of glucose biosensors. This potential is largely responsible for attracting researchers to study the conformational properties of this protein. Previously, we showed that an increase in the fluorescence intensity of the fluorescent dye 6-bromoacetyl-2-dimetylaminonaphtalene (BADAN) is linked to the holo-form of the GGBP/H152C mutant in solutions containing sub-denaturing concentrations of guanidine hydrochloride (GdnHCl). It was hypothesized that low GdnHCl concentrations might lead to compaction of the protein, thereby facilitating ligand binding. In this work, we utilize …
Sertoli Cells Loaded With Doxorubicin In Lipid Micelles Reduced Tumor Burden And Dox-Induced Toxicity, Mahasweta Das, Mark Howell, Elspeth A. Foran, Rohit Iyre, Shyam S. Mohapatra, Subhra Mohapatra
Sertoli Cells Loaded With Doxorubicin In Lipid Micelles Reduced Tumor Burden And Dox-Induced Toxicity, Mahasweta Das, Mark Howell, Elspeth A. Foran, Rohit Iyre, Shyam S. Mohapatra, Subhra Mohapatra
Molecular Medicine Faculty Publications
The toxic side effects of doxorubicin (Dox) limit its long-term use as a lung cancer chemotherapeutic. Additionally, drug delivery to the deep lung is challenging. To address these challenges, isolated rat Sertoli cells (SCs) were preloaded with Dox conjugated to lipid micelle nanoparticles (SC-DLMNs) and delivered to mouse lungs. These immunocompetent cells, when injected intravenously, travel to the lung, deliver the payload, and get cleared by the system quickly without causing any adverse reaction. We observed that SC-DLMNs effectively treated Lewis lung carcinoma 1-induced lung tumors in mice and the drug efficacy was comparable to SC-Dox treatment. Mice treated with …