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Article ; Online: miR-142: A Master Regulator in Hematological Malignancies and Therapeutic Opportunities.

Huang, Wilson / Paul, Doru / Calin, George A / Bayraktar, Recep

2023 Volume 13, Issue 1

Abstract: MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological ... ...

Abstract	MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias. This review elucidates the multifaceted role of miR-142 in human physiology, its influence on hematopoiesis and hematopoietic cells, and its intriguing involvement in exosome-mediated miR-142 transport. Moreover, we offer a comprehensive exploration of the genetic and molecular landscape of the miR-142 genomic locus, highlighting its mutations and dysregulation within hematological malignancies. Finally, we discuss potential avenues for harnessing the therapeutic potential of miR-142 in the context of hematological malignancies.
MeSH term(s)	Humans ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/therapy ; Leukemia/genetics ; Leukemia/therapy ; Exosomes/genetics ; Genomics ; MicroRNAs/genetics
Chemical Substances	MicroRNAs ; MIRN142 microRNA, human
Language	English
Publishing date	2023-12-30
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13010084
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Tumor proliferation and invasion are intrinsically coupled and unraveled through tunable spheroid and physics-based models.

Crawford, Ashleigh J / Gomez-Cruz, Clara / Russo, Gabriella C / Huang, Wilson / Bhorkar, Isha / Roy, Triya / Muñoz-Barrutia, Arrate / Wirtz, Denis / Garcia-Gonzalez, Daniel

Acta biomaterialia

2023 Volume 175, Page(s) 170–185

Abstract: Proliferation and invasion are two key drivers of tumor growth that are traditionally considered independent multicellular processes. However, these processes are intrinsically coupled through a maximum carrying capacity, i.e., the maximum spatial cell ... ...

Abstract	Proliferation and invasion are two key drivers of tumor growth that are traditionally considered independent multicellular processes. However, these processes are intrinsically coupled through a maximum carrying capacity, i.e., the maximum spatial cell concentration supported by the tumor volume, total cell count, nutrient access, and mechanical properties of the tissue stroma. We explored this coupling of proliferation and invasion through in vitro and in silico methods where we modulated the mechanical properties of the tumor and the surrounding extracellular matrix. E-cadherin expression and stromal collagen concentration were manipulated in a tunable breast cancer spheroid to determine the overall impacts of these tumor variables on net tumor proliferation and continuum invasion. We integrated these results into a mixed-constitutive formulation to computationally delineate the influences of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix on net proliferation and continuum invasion. This framework integrates biological in vitro data into concise computational models of invasion and proliferation to provide more detailed physical insights into the coupling of these key tumor processes and tumor growth. STATEMENT OF SIGNIFICANCE: Tumor growth involves expansion into the collagen-rich stroma through intrinsic coupling of proliferation and invasion within the tumor continuum. These processes are regulated by a maximum carrying capacity that is determined by the total cell count, tumor volume, nutrient access, and mechanical properties of the surrounding stroma. The influences of biomechanical parameters (i.e., stiffness, cell elongation, net proliferation rate and cell-ECM friction) on tumor proliferation or invasion cannot be unraveled using experimental methods alone. By pairing a tunable spheroid system with computational modeling, we delineated the interdependencies of each system parameter on tumor proliferation and continuum invasion, and established a concise computational framework for studying tumor mechanobiology.
MeSH term(s)	Humans ; Female ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Breast Neoplasms/pathology ; Physics ; Cell Proliferation ; Cell Line, Tumor ; Tumor Microenvironment
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2023-12-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2023.12.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: LOCALIZED PECTUS EXCAVATUM TREATED WITH BRACE AND EXERCISE: LONG TERM RESULTS OF A BRAZILIAN TECHNIQUE.

Haje, Davi DE Podestá / Haje, Sydney Abrão / Volpon, José Batista / Silva, Ana Carolina Oliveira DA / Lima, Leonardo Ferreira Braz / Huang, Wilson

Acta ortopedica brasileira

2021 Volume 29, Issue 3, Page(s) 143–148

Abstract: Objective: Pectus excavatum is a deformity that affects aesthetics and causes emotional disorders. Surgical correction is well established, but conservative treatment is less common. We investigated the long-term results of using a brace and performing ... ...

Abstract	Objective: Pectus excavatum is a deformity that affects aesthetics and causes emotional disorders. Surgical correction is well established, but conservative treatment is less common. We investigated the long-term results of using a brace and performing specific physical exercises to treat localized pectus excavatum, a type of deformity in which the depressed area is restricted to the midline region along the nipple line. Methods: We selected 115 patients (mean age 12.8 years), with a minimum follow-up of 36 months, who were evaluated more than one year after the end of treatment and skeletal maturity. Results were correlated with deformity flexibility, severity, regular use of the device, and performance of specific exercises. The chi-square (χ Results: Treatment was successful in 58% of patients, however, when exercises were performed and the brace was used regularly by patients with flexible deformities, the rate increased to 83% (p = 0.005). Severity and adherence to treatment greatly impacted successful treatment (p = 0.009 and < 0.001, respectively). Conclusion: The proposed treatment method was effective for correction or partial correction of the deformity in motivated patients followed up until skeletal maturity, especially when started early in milder and more flexible deformities.
Language	English
Publishing date	2021-07-14
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2105206-2
ISSN	1809-4406 ; 1413-7852
ISSN (online)	1809-4406
ISSN	1413-7852
DOI	10.1590/1413-785220212903241550
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Article: BROAD PECTUS EXCAVATUM TREATMENT: LONG TERM RESULTS OF A BRAZILIAN TECHNIQUE.

Haje, Davi de Podestá / Haje, Sydney Abrão / Volpon, José Batista / da Silva, Ana Carolina Oliveira / Lima, Leonardo Ferreira Braz / Huang, Wilson

Acta ortopedica brasileira

2021 Volume 29, Issue 4, Page(s) 197–202

Abstract: Objective: This study aims the treatment results of broad pectus excavatum after a long-term follow-up and skeletal maturity.: Methods: Eighty-four children and adolescents with broad-type pectus excavatum were selected for evaluation after treatment ...

Abstract	Objective: This study aims the treatment results of broad pectus excavatum after a long-term follow-up and skeletal maturity. Methods: Eighty-four children and adolescents with broad-type pectus excavatum were selected for evaluation after treatment with a dynamic orthosis that applies compression to the lower rib projections and prescription of exercises. The broad pectus excavatum was defined as a deformity that the depressed area was greater and covered the area above and below the nipple line. All patients were evaluated for more than 1 year after the end of treatment and skeletal maturity. Post-treatment results were categorized as mild, moderate and severe. Statistic correlations between results and deformity flexibility, deformity severity, and adherence to treatment were assessed. Results: The mean age at the beginning of treatment was 13.3 years, and the follow-up duration was 25.7 months after suspension of orthosis use. Forty-eight percent of patients showed good results. With regular use of orthoses and performance of exercises, this rate increased to 70% (p < 0,001). Mild cases showed more success than severe cases (p = 0,007). Initial flexibility didn't influence the results (p = 0,63). Conclusion: Treatment of broad pectus excavatum with orthoses and exercises led to good definitive results in most resilient patients, especially in those with mild deformities.
Language	English
Publishing date	2021-09-09
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2105206-2
ISSN	1809-4406 ; 1413-7852
ISSN (online)	1809-4406
ISSN	1413-7852
DOI	10.1590/1413-785220212904243419
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Article ; Online: Room Temperature Isothermal Colorimetric Padlock Probe Rolling Circle Amplification for Viral RNA Detection

Huang, Wilson / Hsu, Hannah / Su, Jimmy / Clapper, Jude / Hsu, Jonathan

bioRxiv

Abstract: Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in ... ...

Abstract	Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.06.12.128876
Database	COVID19

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Article ; Online: Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression.

Parks, Cassie A / Pak, Katherine / Pinal-Fernandez, Iago / Huang, Wilson / Derfoul, Assia / Mammen, Andrew L

Scientific reports

2019 Volume 9, Issue 1, Page(s) 18507

Abstract: The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to ... ...

Abstract	The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.
MeSH term(s)	Animals ; Body Weight ; Cardiotoxins ; Cell Survival ; Cholecystokinin/metabolism ; Exons ; Female ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal/metabolism ; RNA-Seq ; Regeneration ; Satellite Cells, Skeletal Muscle/metabolism ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	Cardiotoxins ; Transcription Factors ; Trim33 protein, mouse ; Cholecystokinin (9011-97-6)
Language	English
Publishing date	2019-12-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-54651-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Precision-engineered biomimetics: the human fallopian tube.

Crawford, Ashleigh J / Forjaz, André / Bhorkar, Isha / Roy, Triya / Schell, David / Queiroga, Vasco / Ren, Kehan / Kramer, Donald / Bons, Joanna / Huang, Wilson / Russo, Gabriella C / Lee, Meng-Horng / Schilling, Birgit / Wu, Pei-Hsun / Shih, Ie-Ming / Wang, Tian-Li / Kiemen, Ashley / Wirtz, Denis

bioRxiv : the preprint server for biology

2023

Abstract: The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models to study its pathophysiology. The state-of-the-art organoid model has been ... ...

Abstract	The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models to study its pathophysiology. The state-of-the-art organoid model has been compared to two-dimensional tissue sections and molecularly assessed providing only cursory analyses of the model's accuracy. We developed a novel multi-compartment organoid model of the human fallopian tube that was meticulously tuned to reflect the compartmentalization and heterogeneity of the tissue's composition. We validated this organoid's molecular expression patterns, cilia-driven transport function, and structural accuracy through a highly iterative platform wherein organoids are compared to a three-dimensional, single-cell resolution reference map of a healthy, transplantation-quality human fallopian tube. This organoid model was precision-engineered to match the human microanatomy. One sentence summary: Tunable organoid modeling and CODA architectural quantification in tandem help design a tissue-validated organoid model.
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.06.543923
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Room Temperature Isothermal Colorimetric Padlock Probe Rolling Circle Amplification for Viral RNA Detection

Huang, Wilson / Hsu, Hannah / Su, Jimmy / Clapper, Jude C. / Hsu, Jonathan

bioRxiv

Abstract	Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.
Keywords	covid19
Language	English
Publishing date	2020-06-12
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.06.12.128876
Database	COVID19

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Article ; Online: Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria for Idiopathic Inflammatory Myopathies in Patients With Myositis-Specific Autoantibodies.

Casal-Dominguez, Maria / Pinal-Fernandez, Iago / Pak, Katherine / Huang, Wilson / Selva-O'Callaghan, Albert / Albayda, Jemima / Casciola-Rosen, Livia / Paik, Julie J / Tiniakou, Eleni / Mecoli, Christopher A / Lloyd, Thomas E / Danoff, Sonye K / Christopher-Stine, Lisa / Mammen, Andrew L

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 3, Page(s) 508–517

Abstract: Objective: We undertook this study to 1) determine the sensitivity of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) to properly ...

Abstract	Objective: We undertook this study to 1) determine the sensitivity of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) to properly classify myositis-specific autoantibody (MSA)-positive myositis patients, 2) describe the phenotype and muscle involvement over time in different MSA-positive patients, and 3) compare MSA subgroups to EULAR/ACR criteria-defined myositis subgroups for their capacity to predict clinical phenotypes in patients with IIMs. Methods: The study included 524 MSA-positive myositis patients from the Johns Hopkins Myositis Center. Each patient was classified using the EULAR/ACR classification criteria. Patient phenotypes were summarized using factor analysis of mixed data (FAMD). We compared the ability of MSAs to that of the EULAR/ACR classification subgroups to predict the phenotype of patients by applying the Akaike information criterion (AIC) and the Bayesian information criteria (BIC) to the linear regression models. Results: Overall, 91% of MSA-positive patients met the EULAR/ACR criteria to be classified as having myositis. However, 20% of patients with anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) and 50% of patients with anti-PL-7 were incorrectly classified as not having myositis. Furthermore, ~10% of patients with anti-signal recognition particle (anti-SRP) and patients with anti-HMGCR were misclassified as having inclusion body myositis. FAMD demonstrated that patients within each MSA-defined subgroup had similar phenotypes. Application of both the AIC and BIC to the linear regression models revealed that MSAs were better predictors of myositis phenotypes than the subgroups defined by the EULAR/ACR criteria. Conclusion: Although the EULAR/ACR criteria successfully classified 91% of MSA-positive myositis patients, certain MSA-defined subgroups, including those with autoantibodies against HMGCR, SRP, and PL-7, are frequently misclassified. In myositis patients with MSAs, autoantibodies outperform the EULAR/ACR-defined myositis subgroups in predicting the clinical phenotypes of patients. These findings underscore the need to include MSAs in a revised myositis classification scheme.
MeSH term(s)	Adult ; Aged ; Autoantibodies ; Female ; Humans ; Male ; Middle Aged ; Myositis/classification ; Myositis/diagnosis ; Myositis/immunology ; Phenotype ; Rheumatology
Chemical Substances	Autoantibodies
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.41964
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Stimulation of Hair Growth by Small Molecules that Activate Autophagy.

Chai, Min / Jiang, Meisheng / Vergnes, Laurent / Fu, Xudong / de Barros, Stéphanie C / Doan, Ngan B / Huang, Wilson / Chu, Jessie / Jiao, Jing / Herschman, Harvey / Crooks, Gay M / Reue, Karen / Huang, Jing

Cell reports

2019 Volume 27, Issue 12, Page(s) 3413–3421.e3

Abstract: Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide, but methods that can be used to regrow hair are lacking. We report that quiescent ( ... ...

Abstract	Hair plays important roles, ranging from the conservation of body heat to the preservation of psychological well-being. Hair loss or alopecia affects millions worldwide, but methods that can be used to regrow hair are lacking. We report that quiescent (telogen) hair follicles can be stimulated to initiate anagen and hair growth by small molecules that activate autophagy, including the metabolites α-ketoglutarate (α-KG) and α-ketobutyrate (α-KB), and the prescription drugs rapamycin and metformin, which impinge on mTOR and AMPK signaling. Stimulation of hair growth by these agents is blocked by specific autophagy inhibitors, suggesting a mechanistic link between autophagy and hair regeneration. Consistently, increased autophagy is detected upon anagen entry during the natural hair follicle cycle, and oral α-KB prevents hair loss in aged mice. Our finding that anagen can be pharmacologically activated in telogen skin when natural anagen-inducing signal(s) are absent has implications for the treatment of hair loss patients.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Aging/drug effects ; Aging/metabolism ; Aging/physiology ; Allyl Compounds/pharmacology ; Alopecia/drug therapy ; Alopecia/genetics ; Alopecia/metabolism ; Animals ; Autophagy/drug effects ; Autophagy/genetics ; Butyrates/pharmacology ; Cell Division/drug effects ; Cell Division/genetics ; Female ; Hair/drug effects ; Hair/growth & development ; Hair Follicle/drug effects ; Hair Follicle/metabolism ; Ketoglutaric Acids/pharmacology ; Male ; Metformin/pharmacology ; Mice ; Mice, Inbred C57BL ; Oligomycins/pharmacology ; Quinazolines/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	6-bromo-4-allylamino-quinazoline ; Allyl Compounds ; Butyrates ; Ketoglutaric Acids ; Oligomycins ; Quinazolines ; alpha-ketobutyric acid (600-18-0) ; Metformin (9100L32L2N) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2019-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.05.070
Database	MEDical Literature Analysis and Retrieval System OnLINE

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