27 results on '"Toma MA"'
Search Results
2. CLINICAL ASPECTS OF COMPLEX ORAL REHABILITATION IN PATIENTS WITH DYSFUNCTIONAL SYNDROME OF THE STOMATOGNAT SYSTEM AND ITS INTERFERENCES WITH SCHIZOPHRENIA – Part 1
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Lucian Stefan Burlea, Ana Maria Ciubara, Veronica Serban Pintiliciuc, Tudor Hamburda, Ovidiu Stamatin, Liana Aminov, Bogdan Constantin Mihaila, Doriana Agop Forna, Toma Marius Cristian, and Laura Elisabeta Checherita
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oral rehabilitation ,stomatognathic system ,schizophrenia ,prosthetic treatments ,therapeutic solutions ,dysfunctional syndrome of stomatognathic system (sdss) ,Dentistry ,RK1-715 - Abstract
Dysfunctional syndrome of the stomatognathic system interferes with interferes with many pathologies among which in the present situation, with the characteristics of complex psychiatric pathology. There are cases with a high index of complexity that can be treated only by interdisciplinary approach dentistry-psychiatry. Complex oral rehabilitation imposes strategies and treatments to facilitate a good result in increasing the quality of life and the optimum result of patients with schizophrenia-type psychiatric elements.
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- 2024
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3. 350 The landscape of microRNA-mediated gene regulation in human skin wound healing and venous ulcers
- Author
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Liu, Z., primary, Zhang, L., additional, Toma, MA., additional, Sommar, P., additional, and Landén, N.X., additional
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- 2021
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4. The Joint Research Centre’s Expertise in Nuclear Safeguards Sample Analysis
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Hernández Ana María Sánchez, Buda Razvan, Casteleyn Karin, Commin Lorelei, D’Amati Francesco, Horta Joan, Le Terrier Arnaud, Mühleisen Artur, Stohr Sarah, Schorlé Hélène, Toma Magdalena, Zuñiga Martin Vargas, Wojnowski Denis, Zsigrai Jozsef, and Mayer Klaus
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Physics ,QC1-999 - Abstract
The Joint Research Centre (JRC) in Karlsruhe, in partnership with the Directorate General for Energy (DG ENER), plays a critical role in ensuring the accurate analysis of nuclear materials, as mandated by the EURATOM Treaty. The Analytical Service at JRC Karlsruhe is dedicated to maintaining the highest standards of quality, accuracy, and traceability in its analytical measurements, with a focus on uranium and plutonium content and isotopic composition. Our laboratory is accredited according to ISO/IEC 17025 and has a proven track record of successful participation in numerous Inter-Laboratory Comparisons (ILCs), demonstrating our expertise and commitment to excellence in nuclear material analysis. We employ a range of analytical methods, including active and passive radiometric techniques and mass spectrometry, to ensure the lowest possible uncertainty in our results. Our laboratory has consistently achieved top performance in various ILCs, showcasing our ability to deliver high-quality results and our dedication to maintaining the highest standards of accuracy and reliability. This is a testament to our rigorous quality control processes and our commitment to staying at the forefront of nuclear material analysis. This paper provides insights into the factors that we believe have contributed to our top performance, including our rigorous quality control processes, our commitment to staff training and development, and our investment in state-of-the-art instrumentation. By sharing our experiences and best practices, we aim to contribute to the advancement of nuclear material accounting and control, safeguards verification, and non-proliferation efforts.
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- 2025
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5. Robotic Process Automation in Higher Education: A Case Study on University Daily Sheets
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TOMA Marian- Vlăduț
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higher education ,robotic process automation ,uipath ,public institutions ,Mathematics ,QA1-939 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Modern higher education institutions have become increasingly reliant on digital technologies to streamline their operations and enhance the learning experience. The automation of daily sheets collection and signing represents a strategic endeavor in this direction, facilitating organized, timely, and efficient data management. The current case study focuses on understanding and developing an automated mechanism for the collection of daily sheets activities in a higher education institution. In this endeavor, the primary objective is to streamline the administrative processes associated with daily activities in a higher educational setup, leveraging the principles of Robotic Process Automation to efficiently collect, process, analyze and sign documents related to these activities.
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- 2023
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6. The role of development interventions in enhancing technical efficiency of sunflower producers
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Toma Mamgbi Zozimo, Geoffrey Kawube, and Stephen W. Kalule
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Policy analysis ,Efficiency ,Production techniques ,Agriculture (General) ,S1-972 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
A key policy concern in African agriculture is low productivity even when new technologies are generated, disseminated and adopted among farmers. This study used a cross-sectional dataset from a sample of 202 sunflower farmers drawn from northern Uganda to determine technical efficiency and assess the influence of farmer management capabilities, development intervention and socio-economic factors on technical efficiency. Results reveal that technical inefficiency among sunflower farmers account for 81% of farm-level output. Further, farmer management capabilities (p
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- 2023
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7. Targeting acidic pre-metastatic niche in lungs by pH low insertion peptide and its utility for anti-metastatic therapy
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Toma Matsui, Yuki Toda, Haruka Sato, Rina Itagaki, Kazuya Konishi, Anna Moshnikova, Oleg A. Andreev, Shigekuni Hosogi, Yana K. Reshetnyak, and Eishi Ashihara
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extracellular acidity ,pre-metastatic niche ,pH low insertion peptide ,metabolic reprogramming ,extracellular vesicle ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Dysregulated extracellular pH, the universal feature of tumor, works as an evolutional force to drive dissemination of tumor cells. It is well-established that tumor acidity is associated with tumor growth and metastasis. However, the pH of pre-metastatic niche remains unclear. We hypothesized that primary tumor cells remotely prime acidity in secondary organ to achieve metastatic colonization. Herein, we demonstrated that the pH responsive probe pH Low Insertion Peptide (pHLIP) was notably accumulated in pre-metastatic lungs of 4T1.2 breast tumor-bearing mice. The pHLIP-targeted lungs showed high amounts of lactate and overexpressed glycolysis-related proteins. Pharmacological inhibition of glycolysis suppressed the lung acidification induced by 4T1.2 cancer cell culture supernatant and delayed subsequent metastatic burden of disseminated tumor cells. In the acidic lungs, pHLIP was primarily localized in alveolar type 2 cells which strongly expressed glycolysis-related proteins. 4T1.2-derived extracellular vesicles expressed some of the glycolysis-related proteins, and their administration increased pHLIP accumulation and glycolytic enhancement in lungs. pHLIP-conjugated dexamethasone effectively attenuated lung metastatic burden by disrupting pro-inflammatory response in the acidic lungs. From these results, targeting the metastasis-supporting microenvironment by pHLIP technology creates possibility to identify pre-metastatic organ and prevent metastatic recurrence.
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- 2023
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8. Pat Barker, Šutnja djevojaka
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Toma Marušić
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Ancient history ,D51-90 ,Greek language and literature. Latin language and literature ,PA - Published
- 2024
9. Impact of Costing and Cost Analysis Methods on the Result of the Period: Methods Based on Partial Cost Theory
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Toma Maria
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partial cost ,variable cost ,fixed cost ,Business ,HF5001-6182 ,Economics as a science ,HB71-74 - Abstract
Cost diagnosis is a tool for controlling, regulating, and piloting an enterprise's performance in a competitive economy. Understanding the complete and complex analysis and perceived investigation of resource consumption in an enterprise requires: a good knowledge of subordinate concepts, cost typology, cost analysis methods, calculation methods and unit cost analysis, implicit the cost and strategic decision of the enterprise. Looking from this perspective, in the present paper we have proposed that objectives, to approach the full cost calculation methods based on partial costs (direct-costing on the product or direct-costing evolved), and comparing them to determine the effect they have on the outcome of the period.
- Published
- 2017
10. Impact of Costing and Cost Analysis Methods on the Result of the Period: Methods Based on Full Cost Theory
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Toma Maria
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full cost ,traditional cost ,economic cost ,Business ,HF5001-6182 ,Economics as a science ,HB71-74 - Abstract
Analysis of an enterprise's performance through the net result of the year is not significant because it takes into account financial elements and profit tax. Also, the result of the exercise is directly influenced by:- Accounting Policies for Recording Consumption, either as an expense in the income statement or as an asset on the balance sheet;- The ratio between the charges attributable to the products and those considered for the period;- The costing method used by the enterprise. Assessing the real effort of the enterprise, its results and its difficulties requires analytical investigation of the outcome of the period, the conditions of training and the determining factors of action. In light of the above, in the present paper we have proposed that objectives, to approach the methods of calculating full costs (economic or traditional), and comparing them to determine the effect they have on the outcome of the period.
- Published
- 2017
11. Vector bundles on blown-up Hopf surfaces
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Toma Matei
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32g13 ,32j15 ,compact complex surfaces ,moduli spaces ,hopf surfaces ,vector bundles ,Mathematics ,QA1-939 - Published
- 2012
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12. Direct measurements using on-board diagnostics: study of the dynamics of a vehicle equipped with a DSG automated transmission
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Micu Dan, Fileru Iordan, Toma Marius, and Andreescu Cristian
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
The paper aims to analyze a series of OBD data from a Volkswagen Passat 2.0 tdi, 103 kW, equipped with an automatic DSG transmission, while traveling in the city. Some parameters are analyzed, with a special emphasis on the relation between the engine speed and vehicle speed, presenting also an example of using the information provided by the OBD to determine the gear ratios. The gear steps and the way they are used while driving the vehicle are identified in the end.
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- 2018
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13. The restriction produced by the air filtration system versus the restriction produced by the air filter
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Toma Marius, Stan Cornelia, and Fileru Iordan
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
The air filtration system for an internal combustion engine comprises the air filter, the filter housing and the intake air duct which conducts the air flow from the vehicle grille to the filter housing. This generates gaso-dynamic resistances to the air intake into the engine. The air filter housing and the intake air duct are often mounted in the engine compartment mainly where it fits better and less according to the air flow and noise reduction criteria. The paper aims to show the contribution of the restriction produced by the filter housing and the intake air duct to the total restriction produced by the air filtration system. Several air filtration systems from vehicles fitted with both spark-ignition engines and diesel engines are tested. The results show that the restriction produced by the intake air duct system as well as the air filter housing have a significant contribution to the total restriction produced by the air filtration system of a vehicle engine.
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- 2018
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14. Comparative study on the lateral run-out of friction surfaces measurement of brake discs using a brake roller tester and a dial gauge
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Toma Marius, Andreescu Cristian, and Micu Dan
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
Brake system diagnosis is one of the most common and necessary technical operations applied to the car, regardless of its type and operating phases. Measuring the diagnostic parameters on a roller brake tester is a fast operation with no disassembly necessary. Measuring the run-out of friction surfaces of brake discs with a dial gauge is an action that requires more extensive preparatory operations but it offers a high accuracy of the results. The paper aims to analyze the correlation between the dial gauge measured values and the diagnostic obtained using the brake roller tester.
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- 2017
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15. Circular RNA circASH1L(4,5) protects microRNA-129-5p from target-directed microRNA degradation in human skin wound healing.
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Wang Q, Niu G, Liu Z, Toma MA, Geara J, Bian X, Zhang L, Piipponen M, Li D, Wang A, Sommar P, and Xu Landén N
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Background: Skin wound healing involves a complex gene expression program that remains largely undiscovered in humans. Circular RNAs (circRNAs) and microRNAs (miRNAs) are key players in this process., Objectives: To understand the functions and potential interactions of circRNAs and miRNAs in human skin wound healing., Methods: CircRNA, linear RNA, and miRNA expression in human acute and chronic wounds were analyzed using RNA sequencing and qRT-PCR. The roles of circASH1L(4,5) and miR-129-5p were studied in human primary keratinocytes (proliferation and migration assays, microarray analysis) and ex vivo wound models (histological analysis). The interaction between circASH1L(4,5) and miR-129-5p was examined using luciferase reporter and RNA pull-down assays., Results: We identified circASH1L(4,5) and its interaction with miR-129-5p, both of which increased during human skin wound healing. Unlike typical miRNA sponging, circASH1L enhanced miR-129 stability and silencing activity by protecting it from target-directed degradation triggered by NR6A1 mRNA. TGF-β signaling, crucial in wound healing, promoted circASH1L expression while suppressing NR6A1, thereby increasing miR-129 abundance at the post-transcriptional level. CircASH1L and miR-129 enhanced keratinocyte migration and proliferation, crucial for re-epithelialization of human wounds., Conclusions: Our study uncovers a novel role for circRNAs as protectors of miRNAs and highlights the importance of regulated miRNA degradation in skin wound healing., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)
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- 2024
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16. Recent advances in probiotication of fruit and vegetable juices.
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Rahman MS, Emon DD, Toma MA, Nupur AH, Karmoker P, Iqbal A, Aziz MG, and Alim MA
- Abstract
Probiotics are live bacteria beneficial to health when consumed adequately. Health professionals now recommend probiotics on regular diets due to their positive effects on human health. The probiotics that are usually consumed from the market through food products are mostly dairy-based. Fruit and vegetables are gaining popularity as preferred matrices for probiotic carriers to the human body, owing to their high cholesterol content and the lactose intolerance of dairy products. On the other hand, fruits and vegetable juices are rich in nutrient content such as vitamins, minerals, and antioxidants and do not contain a starter culture that can compete with the nutrients. The probiotication of fruit and vegetable juices (apple, carrot, citrus fruit, pome-granate, watermelon, tomato, and pineapple) are performing as efficient probiotic bacteria carriers. This review covers the previous works that highlighted the variety of probiotic fruit and vegetable juices as well as the viability of each probiotic in various products after proper fermentation and storage. In addition, physicochemical and sensory changes that occurred during the processing and storage period have been discussed. Furthermore, strategies (microencapsulation, adding prebiotics, antioxidant addition, maintaining optimum pH, temperature, adaptation with resistance, and good packaging) to improve the stability of probiotic bacteria are outlined, as it is difficult to maintain the stability of probiotic bacteria during storage. Finally, the manuscript discusses the effect of probiotic fruit and vegetable juices on human health., Competing Interests: The authors declare no conflict of interest., (Copyright: © Journal of Advanced Veterinary and Animal Research.)
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- 2023
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17. Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport.
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Zhang L, Piipponen M, Liu Z, Li D, Bian X, Niu G, Geara J, Toma MA, Sommar P, and Xu Landén N
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- Animals, Humans, Skin metabolism, Keratinocytes metabolism, Epidermis metabolism, Cell Differentiation physiology, Transcription Factors metabolism, Endoplasmic Reticulum metabolism, Mammals metabolism, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
After a skin injury, keratinocytes switch from a state of homeostasis to one of regeneration leading to the reconstruction of the epidermal barrier. The regulatory mechanism of gene expression underpinning this key switch during human skin wound healing is enigmatic. Long noncoding RNAs (lncRNAs) constitute a new horizon in the understanding of the regulatory programs encoded in the mammalian genome. By comparing the transcriptome of an acute human wound and skin from the same donor as well as keratinocytes isolated from these paired tissue samples, we generated a list of lncRNAs showing changed expression in keratinocytes during wound repair. Our study focused on HOXC13-AS, a recently evolved human lncRNA specifically expressed in epidermal keratinocytes, and we found that its expression was temporally downregulated during wound healing. In line with its enrichment in suprabasal keratinocytes, HOXC13-AS was found to be increasingly expressed during keratinocyte differentiation, but its expression was reduced by EGFR signaling. After HOXC13-AS knockdown or overexpression in human primary keratinocytes undergoing differentiation induced by cell suspension or calcium treatment and in organotypic epidermis, we found that HOXC13-AS promoted keratinocyte differentiation. Moreover, RNA pull-down assays followed by mass spectrometry and RNA immunoprecipitation analysis revealed that mechanistically HOXC13-AS sequestered the coat complex subunit alpha (COPA) protein and interfered with Golgi-to-endoplasmic reticulum (ER) molecular transport, resulting in ER stress and enhanced keratinocyte differentiation. In summary, we identified HOXC13-AS as a crucial regulator of human epidermal differentiation., (© 2023. The Author(s).)
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- 2023
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18. Circular RNA Signatures of Human Healing and Nonhealing Wounds.
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Toma MA, Liu Z, Wang Q, Zhang L, Li D, Sommar P, and Landén NX
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- Cell Movement genetics, Gene Expression Profiling, Gene Regulatory Networks, Humans, Membrane Glycoproteins genetics, RNA genetics, RNA metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Sulfotransferases genetics, MicroRNAs genetics, MicroRNAs metabolism, RNA, Circular genetics
- Abstract
Venous ulcers (VUs) have complex and obscure pathogenicity, and effective VU therapies are still lacking. Circular RNAs (circRNAs) have emerged as powerful gene regulators with important roles in health and disease. In this study, we used paired total RNA and small RNA sequencing to profile circRNAs, protein-coding mRNAs, and microRNAs expression in a unique collection of clinical samples: healthy skin and acute wounds at inflammatory and proliferative phases and wound-edge VU biopsies. We unravel a dynamically changed expression pattern of circRNAs during human skin repair and their abnormal expression signature in VU, which are presented as a searchable web resource (www.xulandenlab.com/humanwounds-circrna). We analyzed the coexpression relationship between the circRNAs and mRNAs with weighted correlation network analysis and constructed circRNA‒mRNA‒microRNA networks. This allowed us to expose the regulatory networks specific to the inflammatory and proliferative phases of wound repair and VU, the biological processes the circRNAs may regulate, and the circRNAs that could sponge microRNAs in human wounds. Importantly, we found that hsa-CHST15_0003 and hsa-TNFRSF21_0001, two circRNAs upregulated in VU, hampered epidermal keratinocyte migration while promoting proliferation by modulating gene networks underpinning these cellular processes. This study paves the way to decipher the functional significance of circRNAs in tissue repair., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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19. Integrative small and long RNA omics analysis of human healing and nonhealing wounds discovers cooperating microRNAs as therapeutic targets.
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Liu Z, Zhang L, Toma MA, Li D, Bian X, Pastar I, Tomic-Canic M, Sommar P, and Xu Landén N
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- Gene Expression Regulation, Humans, RNA, Messenger metabolism, Skin metabolism, Wound Healing genetics, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed paired small and long RNA-sequencing and integrative omics analysis in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic nonhealing venous ulcers (VUs). On the basis of the findings, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte migration and growth while promoting inflammatory response. By combining miR expression patterns with their specific target gene expression context, we identified miRs highly relevant to VU pathology. Our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity., Competing Interests: ZL, LZ, MT, DL, XB, PS, NX No competing interests declared, IP is on the Board of Directors for the Wound Healing Society. Irena Pastar received payment for speaking at the Symposium of Advanced Wound Care and Wound Healing Society 2022 meeting, and the World Union of the Wound Healing Societies 2022. The author has no other competing interests to declare, MT received grants from NIH/NIDDK [U01DK119085], NIH/NINR [R01NR015649], NIH/NIDDK [U24DK115255] and NIH/NIDDK [R41DK127900] for research unrelated to the topic of the manuscript. Marjana Tomic-Canic received payment for attending, speaking and moderating at the Symposium of Advanced Wound Care and Wound Healing Society 2022 meeting, and for attending the World Union of the Wound Healing Societies 2022. Marjana Tomic-Canic participates on the Scientific Advisory Board of Molnlycke. The patent No. 63/335,306 "Theraputic Compositions" is pending. The author has no other competing interests to declare, (© 2022, Liu, Zhang et al.)
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- 2022
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20. Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes.
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Li D, Cheng S, Pei Y, Sommar P, Kärner J, Herter EK, Toma MA, Zhang L, Pham K, Cheung YT, Liu Z, Chen X, Eidsmo L, Deng Q, and Xu Landén N
- Subjects
- Aged, Humans, Keratinocytes metabolism, Major Histocompatibility Complex, Single-Cell Analysis, Wound Healing genetics, Pressure Ulcer
- Abstract
Pressure ulcer (PU) is a chronic wound often seen in patients with spinal cord injury and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. In this study, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II‒expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN-γ in PU-derived wound fluid could induce major histocompatibility complex II expression in keratinocytes and that these wound fluid‒treated keratinocytes inhibited autologous T-cell activation. In line with this observation, we found that T cells from PUs enriched with major histocompatibility complex II
+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared with that of acute wounds and intact skin, providing insights into PU pathology and the future development of tailored wound therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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21. Isolation and Identification of Natural Colorant Producing Soil-Borne Aspergillus niger from Bangladesh and Extraction of the Pigment.
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Toma MA, Nazir KHMNH, Mahmud MM, Mishra P, Ali MK, Kabir A, Shahid MAH, Siddique MP, and Alim MA
- Abstract
Natural colorants have been used in several ways throughout human history, such as in food, dyes, pharmaceuticals, cosmetics, and many other products. The study aimed to isolate the natural colorant-producing filamentous fungi Aspergillus niger from soil and extract pigments for its potential use specially for food production. Fourteen soil samples were collected from Madhupur National Park at Madhupur Upazila in the Mymensingh district, Bangladesh. The Aspergillus niger was isolated and identified from the soil samples by following conventional mycological methods (cultural and morphological characteristics), followed by confirmatory identification by a polymerase chain reaction (PCR) of conserved sequences of ITS1 ribosomal DNA using specific oligonucleotide primers. This was followed by genus- and species-specific primers targeting Aspergillus niger with an amplicon size of 521 and 310 bp, respectively. For pigment production, a mass culture of Aspergillus niger was conducted in Sabouraud dextrose broth in shaking conditions for seven days. The biomass was subjected to extraction of the pigments following an ethanol-based extraction method and concentrated using a rotary evaporator. Aspergillus niger could be isolated from three samples. The yield of extracted brown pigment from Aspergillus niger was 0.75% ( w / v ). Spectroscopic analysis of the pigments was carried out using a UV-VIS spectrophotometer. An in vivo experiment was conducted with mice to assess the toxicity of the pigments. From the colorimetric and sensory evaluations, pigment-supplemented products (cookies and lemon juice) were found to be more acceptable than the control products. This could be the first attempt to use Aspergillus niger extracted pigment from soil samples in food products in Bangladesh, but for successful food production, the food colorants must be approved by a responsible authority, e.g., the FDA or the BSTI. Moreover, fungal pigments could be used in the emerging fields of the food and textile industries in Bangladesh.
- Published
- 2021
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22. HutW from Vibrio cholerae Is an Anaerobic Heme-Degrading Enzyme with Unique Functional Properties.
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Brimberry M, Toma MA, Hines KM, and Lanzilotta WN
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- Anaerobiosis, Bacterial Outer Membrane Proteins chemistry, Gene Expression Regulation, Bacterial, Methyltransferases chemistry, Protein Conformation, S-Adenosylmethionine metabolism, Bacterial Outer Membrane Proteins metabolism, Heme metabolism, Methyltransferases metabolism, NADP metabolism, Tetrapyrroles chemistry, Vibrio cholerae enzymology
- Abstract
Increasing antibiotic resistance, and a growing recognition of the importance of the human microbiome, demand that new therapeutic targets be identified. Characterization of metabolic pathways that are unique to enteric pathogens represents a promising approach. Iron is often the rate-limiting factor for growth, and Vibrio cholerae , the causative agent of cholera, has been shown to contain numerous genes that function in the acquisition of iron from the environment. Included in this arsenal of genes are operons dedicated to obtaining iron from heme and heme-containing proteins. Given the persistence of cholera, an important outstanding question is whether V. cholerae is capable of anaerobic heme degradation as was recently reported for enterohemorrhagic Escherichia coli O157:H7. In this work, we demonstrate that HutW from V. cholerae is a radical S -adenosylmethionine methyl transferase involved in the anaerobic opening of the porphyrin ring of heme. However, in contrast to the enzyme ChuW, found in enterohemorrhagic E. coli O157:H7, there are notable differences in the mechanism and products of the HutW reaction. Of particular interest are data that demonstrate HutW will catalyze ring opening as well as tetrapyrrole reduction and can utilize reduced nicotinamide adenine dinucleotide phosphate as an electron source. The biochemical and biophysical properties of HutW are presented, and the evolutionary implications are discussed.
- Published
- 2021
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23. Circular RNA hsa_circ_0084443 Is Upregulated in Diabetic Foot Ulcer and Modulates Keratinocyte Migration and Proliferation.
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Wang A, Toma MA, Ma J, Li D, Vij M, Chu T, Wang J, Li X, and Xu Landén N
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- Adult, Aged, Aged, 80 and over, Blotting, Northern, Cohort Studies, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, RNA, Circular metabolism, Real-Time Polymerase Chain Reaction, Transcriptome, Cell Movement genetics, Cell Proliferation genetics, Diabetic Foot genetics, Keratinocytes metabolism, RNA, Circular genetics, Up-Regulation genetics, Wound Healing genetics
- Abstract
Objective: Insufficient knowledge about the molecular pathology of diabetic foot ulcer (DFU) impedes the development of effective wound treatment. Circular RNAs (circRNAs) are a novel class of RNA recently discovered to be widely expressed and have important biological functions; however, their role in skin wound healing remains largely unexplored. In this study, we investigated the role of circRNAs in DFU. Approach: CircRNA expression was profiled in normal wounds (NWs) and DFUs by microarray analysis, and hsa_circ_0084443 was identified as differentially expressed. The circularity and subcellular localization of hsa_circ_0084443 were characterized by northern blotting, real-time PCR, and fluorescence in situ hybridization. Cell migration, cell growth, and the transcriptome of human primary keratinocytes were analyzed after overexpression or RNA interference of hsa_circ_0084443. Results: hsa_circ_0084443 is downregulated in NWs compared with intact skin, and its level is higher in DFUs than NWs. We confirmed its circularity and presence in the cytoplasm of human epidermal keratinocytes. We showed that hsa_circ_0084443 reduced motility while enhancing the growth of keratinocytes. Furthermore, we identified a gene network with the potential to mediate the biological effect of hsa_circ_0084443. Innovation: CircRNAs have a functional role and a potential clinical significance in skin wound healing. Conclusions: We identified hsa_circ_0084443, a circRNA downregulated during NW healing, as a negative regulator of keratinocyte migration. Higher levels of hsa_circ_0084443 were detected in DFU samples, suggesting that it plays a role in pathology. These findings pave the way to understanding the functional role of circRNAs in human skin wound healing., Competing Interests: No competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article., (Copyright © 2020 by Mary Ann Liebert, Inc., publishers.)
- Published
- 2020
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24. MicroRNA-34 Family Enhances Wound Inflammation by Targeting LGR4.
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Wu J, Li X, Li D, Ren X, Li Y, Herter EK, Qian M, Toma MA, Wintler AM, Sérézal IG, Rollman O, Ståhle M, Wikstrom JD, Ye X, and Landén NX
- Subjects
- Aged, Aged, 80 and over, Animals, Biopsy, Cell Movement genetics, Cell Movement immunology, Cell Proliferation genetics, Disease Models, Animal, Female, Gene Expression Regulation immunology, Glycogen Synthase Kinase 3 beta metabolism, Healthy Volunteers, Humans, Keratinocytes, Male, Mice, Mice, Knockout, Middle Aged, Phosphorylation genetics, Phosphorylation immunology, Signal Transduction genetics, Signal Transduction immunology, Skin immunology, Skin pathology, Transcription Factor RelA metabolism, Varicose Ulcer pathology, Wound Healing immunology, MicroRNAs metabolism, Receptors, G-Protein-Coupled genetics, Varicose Ulcer immunology, Wound Healing genetics
- Abstract
Venous ulcers are the most common type of human chronic nonhealing wounds and are stalled in a constant and excessive inflammatory state. The molecular mechanisms underlying the chronic wound inflammation remain elusive. Moreover, little is known about the role of regulatory RNAs, such as microRNAs, in the pathogenesis of venous ulcers. We found that both microRNA (miR)-34a and miR-34c were upregulated in the wound-edge epidermal keratinocytes of venous ulcers compared with normal wounds or the skin. In keratinocytes, miR-34a and miR-34c promoted inflammatory chemokine and cytokine production. In wounds of wild-type mice, miR-34a-mimic treatment enhanced inflammation and delayed healing. To further explore how miR-34 functions, LGR4 was identified as a direct target mediating the proinflammatory function of miR-34a and miR-34c. Interestingly, impaired wound closure with enhanced inflammation was also observed in Lgr4 knockout mice. Mechanistically, the miR-34-LGR4 axis regulated GSK-3β-induced p65 serine 468 phosphorylation, changing the activity of the NF-κB signaling pathway. Collectively, the miR-34-LGR4 axis was shown to regulate keratinocyte inflammatory response, the deregulation of which may play a pathological role in venous ulcers., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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25. WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines.
- Author
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Herter EK, Li D, Toma MA, Vij M, Li X, Visscher D, Wang A, Chu T, Sommar P, Blomqvist L, Berglund D, Ståhle M, Wikstrom JD, and Xu Landén N
- Subjects
- Adult, Aged, Aged, 80 and over, Biopsy, Cell Movement genetics, Cell Movement immunology, Chemokines immunology, Chemokines metabolism, Female, Gene Expression Profiling, Gene Knockdown Techniques, Healthy Volunteers, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Primary Cell Culture, RNA, Long Noncoding genetics, Skin immunology, Skin injuries, Skin pathology, Tissue Culture Techniques, Varicose Ulcer immunology, Varicose Ulcer pathology, Wound Healing genetics, Wound Healing immunology, Young Adult, Chemokines genetics, Gene Expression Regulation immunology, Keratinocytes physiology, RNA, Long Noncoding metabolism, Varicose Ulcer genetics
- Abstract
Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase II-encoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin. In cultured keratinocytes, LOC100130476 expression was induced by TGF-β signaling. By reducing LOC100130476 expression with antisense oligos or activating its transcription with CRISPR/Cas9 Synergistic Activation Mediator system, we showed that LOC100130476 restricted the production of inflammatory chemokines by keratinocytes, while enhancing cell migration. In line with this, knockdown of LOC100130476 impaired re-epithelization of human ex vivo wounds. Based on these results, we named LOC100130476 wound and keratinocyte migration-associated long noncoding RNA 2 (WAKMAR2). Moreover, we identified a molecular network that may mediate the biological function of WAKMAR2 in keratinocytes using microarray. In summary, our data suggest that WAKMAR2 is an important regulator of skin wound healing and its deficiency may contribute to the pathogenesis of chronic wounds., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2019
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26. Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration.
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Li D, Kular L, Vij M, Herter EK, Li X, Wang A, Chu T, Toma MA, Zhang L, Liapi E, Mota A, Blomqvist L, Gallais Sérézal I, Rollman O, Wikstrom JD, Bienko M, Berglund D, Ståhle M, Sommar P, Jagodic M, and Landén NX
- Subjects
- Chronic Disease, E2F1 Transcription Factor metabolism, Gene Expression Regulation, Humans, Keratinocytes pathology, Skin pathology, Transforming Growth Factor beta metabolism, Wounds and Injuries pathology, Cell Movement, Keratinocytes metabolism, RNA, Long Noncoding biosynthesis, Signal Transduction, Skin metabolism, Wound Healing, Wounds and Injuries metabolism
- Abstract
An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed "wound and keratinocyte migration-associated lncRNA 1" (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)
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- 2019
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27. Tripartite symbiosis of Sophora tomentosa, rhizobia and arbuscular mycorhizal fungi.
- Author
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Toma MA, Soares de Carvalho T, Azarias Guimarães A, Martins da Costa E, Savana da Silva J, and de Souza Moreira FM
- Subjects
- Bacteria classification, Bacteria genetics, Bacterial Physiological Phenomena, Fungi classification, Fungi genetics, Fungi physiology, Mycorrhizae classification, Mycorrhizae genetics, Mycorrhizae physiology, Phylogeny, Plant Roots microbiology, Soil Microbiology, Sophora physiology, Bacteria isolation & purification, Fungi isolation & purification, Mycorrhizae isolation & purification, Sophora microbiology, Symbiosis
- Abstract
Sophora tomentosa is a pantropical legume species with potential for recovery of areas degraded by salinization, and for stabilization of sand dunes. However, few studies on this species have been carried out, and none regarding its symbiotic relationship with beneficial soil microorganisms. Therefore, this study aimed to evaluate the diversity of nitrogen-fixing bacteria isolated from nodules of Sophora tomentosa, and to analyze the occurrence of colonization of arbuscular mycorrhizal fungi on the roots of this legume in seafront soil. Thus, seeds, root nodules, and soil from the rhizosphere of Sophora tomentosa were collected. From the soil samples, trap cultures with this species were established to extract spores and to evaluate arbuscular mycorhizal fungi colonization in legume roots, as well as to capture rhizobia. Rhizobia strains were isolated from nodules collected in the field or from the trap cultures. Representative isolates of the groups obtained in the similarity dendrogram, based on phenotypic characteristics, had their 16S rRNA genes sequenced. The legume species showed nodules with indeterminate growth, and reddish color, distributed throughout the root. Fifty-one strains of these nodules were isolated, of which 21 were classified in the genus Bacillus, Brevibacillus, Paenibacillus, Rhizobium and especially Sinorhizobium. Strains closely related to Sinorhizobium adhaerens were the predominant bacteria in nodules. The other genera found, with the exception of Rhizobium, are probably endophytic bacteria in the nodules. Arbuscular mycorrhizal fungi was observed colonizing the roots, but arbuscular mycorhizal fungi spores were not found in the trap cultures. Therefore Sophora tomentosa is associated with both arbuscular mycorhizal fungi and nodulating nitrogen-fixing bacteria., (Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)
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- 2017
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