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Article ; Online: Induced Pluripotent Stem Cells in Drug Discovery and Neurodegenerative Disease Modelling.

Beghini, Daniela Gois / Kasai-Brunswick, Tais Hanae / Henriques-Pons, Andrea

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Induced pluripotent stem cells (iPSCs) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This ... ...

Abstract	Induced pluripotent stem cells (iPSCs) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and much attention has been given to developing iPSC-based disease models to validate drug discovery platforms and study the pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual's bulk of genetic mutations and unique properties. Moreover, iPSCs can differentiate into multiple cell types. These are essential characteristics, since the study of neurological diseases is affected by the limited access to injury sites, the need for in vitro models composed of various cell types, the complexity of reproducing the brain's anatomy, the challenges of postmortem cell culture, and ethical issues. Neurodegenerative diseases strongly impact global health due to their high incidence, symptom severity, and lack of effective therapies. Recently, analyses using disease specific, iPSC-based models confirmed the efficacy of these models for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modelling and drug testing, with a primary focus on neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells ; Neurodegenerative Diseases/drug therapy ; Pluripotent Stem Cells ; Drug Discovery ; Alzheimer Disease
Language	English
Publishing date	2024-02-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042392
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Article ; Online: Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future.

Beghini, Daniela Gois / Horita, Samuel Iwao / Henriques-Pons, Andrea

Cells

2021 Volume 10, Issue 10

Abstract: Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of ... ...

Abstract	Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.
MeSH term(s)	Animals ; COVID-19/blood ; COVID-19/drug therapy ; COVID-19/therapy ; Cell Differentiation ; Cell- and Tissue-Based Therapy ; Culture Media ; Extracellular Vesicles ; Humans ; Inflammation ; Lung/physiology ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, SCID ; Phenotype ; Pneumonia/blood ; Pneumonia/immunology ; Pneumonia/therapy ; Regeneration/physiology ; Respiratory Distress Syndrome ; SARS-CoV-2 ; Thromboembolism/blood ; Thromboembolism/immunology ; Thromboembolism/therapy
Chemical Substances	Culture Media
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10102588
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Article ; Online: Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

Barreto da Silva, Tatiane / Dias, Evellyn Araújo / Cardoso, Liana Monteiro da Fonseca / Gama, Jaciara Fernanda Gomes / Alves, Luiz Anastácio / Henriques-Pons, Andrea

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, ... ...

Abstract	The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.
MeSH term(s)	Humans ; Regenerative Medicine ; Hepatocytes/transplantation ; COVID-19/therapy ; Liver Diseases/therapy ; Stem Cells ; Liver Regeneration ; Nanostructures ; Magnetic Phenomena
Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24119293
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Article ; Online: Analysis of SIKVAV's receptor affinity, pharmacokinetics, and pharmacological characteristics: a matrikine with potent biological function.

Filgueiras, Livia Alves / de Andrade, Francisco das Chagas Pereira / Iwao Horita, Samuel / Shirsat, Shubhangi D / Achal, Varenyam / Rai, Mahendra / Henriques-Pons, Andrea / Mendes, Anderson Nogueira

Journal of biomolecular structure & dynamics

2024 , Page(s) 1–23

Abstract: Matrikines are biologically active peptides generated from fragments fragmentation of extracellular matrix components (ECM) that are functionally distinct from the original full-length molecule. The active matricryptic sites can be unmasked by ECM ... ...

Abstract	Matrikines are biologically active peptides generated from fragments fragmentation of extracellular matrix components (ECM) that are functionally distinct from the original full-length molecule. The active matricryptic sites can be unmasked by ECM components enzymatic degradation or multimerization, heterotypic binding, adsorption to other molecules, cell-mediated mechanical forces, exposure to reactive oxygen species, ECM denaturation, and others. Laminin α1-derived peptide (SIKVAV) is a bioactive peptide derived from laminin-111 that participates in tumor development, cell proliferation, angiogenesis in various cell types. SIKVAV has also a potential pharmaceutical activity that may be used for tissue regeneration and bioengineering in Alzheimer's disease and muscular dystrophies. In this work, we made computational analyzes of SIKVAV regarding the ADMET panel, that stands for Administration, Distribution, Metabolism, Excretion, and Toxicity. Docking analyzes using the α3β1 and α6β1 integrin receptors were performed to fill in the gaps in the SIKVAV's signaling pathway and coupling tests showed that SIKVAV can interact with both receptors. Moreover, there is no indication of cytotoxicity, mutagenic or carcinogenic activity, skin or oral sensitivity. Our analysis suggests that SIKVAV has a high probability of interacting with peroxisome proliferator-activated receptor-gamma (NR-PPAR-γ), which has anti-inflammatory activity. The results of bioinformatics can help understand the participation of SIKVAV in homeostasis and influence the understanding of how this peptide can act as a biological asset in the control of dystrophies, neurodegenerative diseases, and tissue engineering.Communicated by Ramaswamy H. Sarma.
Language	English
Publishing date	2024-02-12
Publishing country	England
Document type	Journal Article
ZDB-ID	49157-3
ISSN	1538-0254 ; 0739-1102
ISSN (online)	1538-0254
ISSN	0739-1102
DOI	10.1080/07391102.2024.2313709
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Article: Influence of leptin and its receptors on individuals under chronic social stress behavior.

Mélo, Renata M F / Barbosa, Rafaela S / Ozório, Victória L / Oliveira, Gabriel M / Horita, Samuel I M / Henriques-Pons, Andrea / Araújo-Jorge, Tânia C / Fragoso, Viviane M S

Frontiers in endocrinology

2024 Volume 15, Page(s) 1281135

Abstract: Stress is the body's physiological reaction to a dangerous or threatening situation, leading to a state of alertness. This reaction is necessary for developing an effective adaptive response to stress and maintaining the body's homeostasis. Chronic ... ...

Abstract	Stress is the body's physiological reaction to a dangerous or threatening situation, leading to a state of alertness. This reaction is necessary for developing an effective adaptive response to stress and maintaining the body's homeostasis. Chronic stress, caused mainly by social stress, is what primarily affects the world's population. In the last decades, the emergence of psychological disorders in humans has become more frequent, and one of the symptoms that can be observed is aggressiveness. In the brain, stress can cause neuronal circuit alterations related to the action of hormones in the central nervous system. Leptin, for example, is a hormone capable of acting in brain regions and neuronal circuits important for behavioral and emotional regulation. This study investigated the correlation between chronic social stress, neuroendocrine disorders, and individual behavioral changes. Then, leptin and its receptors' anatomical distribution were evaluated in the brains of mice subjected to a protocol of chronic social stress. The model of spontaneous aggression (MSA) is based on grouping young mice and posterior regrouping of the same animals as adults. According to the regrouping social stress, we categorized the mice into i) harmonic, ii) attacked, and iii) aggressive animals. For leptin hormone evaluation, we quantified plasma and brain concentrations by ELISA and evaluated its receptor and isoform expression by western blotting. Moreover, we verified whether stress or changes in leptin levels interfered with the animal's body weight. Only attacked animals showed reduced plasma leptin concentration and weight gain, besides a higher expression of the high-molecular-weight leptin receptor in the amygdala and the low-molecular-weight receptor in the hippocampal region. Aggressive animals showed a reduction in the cerebral concentration of leptin in the hippocampus and a reduced high-and low-molecular-weight leptin receptor expression in the amygdala. The harmonic animals showed a reduction in the cerebral concentration of leptin in the pituitary and a reduced expression of the high-molecular-weight leptin receptor in the amygdala. We then suggest that leptin and its receptors' expression in plasma and specific brain areas are involved in how individuals react in stressful situations, such as regrouping stress in MSA.
MeSH term(s)	Adult ; Animals ; Mice ; Body Weight ; Leptin/metabolism ; Receptors, Leptin ; Social Behavior ; Stress, Psychological/metabolism
Chemical Substances	Leptin ; Receptors, Leptin
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1281135
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Article ; Online: Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future

Daniela Gois Beghini / Samuel Iwao Horita / Andrea Henriques-Pons

Cells, Vol 10, Iss 2588, p

2021 Volume 2588

Abstract	Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells’ differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.
Keywords	mesenchymal stem cells ; COVID-19 ; cell therapy ; inflammation ; tissue regeneration ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration.

Henriques-Pons, Andrea / Beghini, Daniela Gois / Silva, Vanessa Dos Santos / Iwao Horita, Samuel / da Silva, Fabrício Alves Barbosa

Frontiers in immunology

2022 Volume 12, Page(s) 780900

Abstract: Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have potent self-renewal capacity and differentiate into multiple cell types. For many reasons, these cells are a promising therapeutic alternative to ... ...

Abstract	Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have potent self-renewal capacity and differentiate into multiple cell types. For many reasons, these cells are a promising therapeutic alternative to treat patients with severe COVID-19 and pulmonary post-COVID sequelae. These cells are not only essential for tissue regeneration; they can also alter the pulmonary environment through the paracrine secretion of several mediators. They can control or promote inflammation, induce other stem cells differentiation, restrain the virus load, and much more. In this work, we performed single-cell RNA-seq data analysis of MSCs in bronchoalveolar lavage samples from control individuals and COVID-19 patients with mild and severe clinical conditions. When we compared samples from mild cases with control individuals, most genes transcriptionally upregulated in COVID-19 were involved in cell proliferation. However, a new set of genes with distinct biological functions was upregulated when we compared severely affected with mild COVID-19 patients. In this analysis, the cells upregulated genes related to cell dispersion/migration and induced the γ-activated sequence (GAS) genes, probably triggered by IFNGR1 and IFNGR2. Then,
MeSH term(s)	Adult ; COVID-19/immunology ; COVID-19/metabolism ; Cell Differentiation/immunology ; Cell Movement/immunology ; Cell Proliferation/physiology ; Cytoplasm/immunology ; Epithelial-Mesenchymal Transition/immunology ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Lung/immunology ; Mesenchymal Stem Cells/immunology ; Mesenchymal Stem Cells/metabolism ; Regeneration/immunology ; SARS-CoV-2/immunology ; Up-Regulation/immunology ; Young Adult
Language	English
Publishing date	2022-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.780900
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Article ; Online: Immunological Tolerance in Liver Transplant Recipients: Putative Involvement of Neuroendocrine-Immune Interactions.

Gama, Jaciara Fernanda Gomes / Cardoso, Liana Monteiro da Fonseca / Bisaggio, Rodrigo da Cunha / Lagrota-Candido, Jussara / Henriques-Pons, Andrea / Alves, Luiz A

Cells

2022 Volume 11, Issue 15

Abstract: The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant ... ...

Abstract	The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant regarding kidney, heart, and lung transplantations at higher frequencies. Most studies have attempted to explain this phenomenon through unique immunological mechanisms and the fact that the hepatic environment is continuously exposed to high levels of pathogen-associated molecular patterns (PAMPs) or non-pathogenic microorganism-associated molecular patterns (MAMPs) from commensal flora. These components are highly inflammatory in the periphery but tolerated in the liver as part of the normal components that arrive via the hepatic portal vein. These immunological mechanisms are discussed herein based on current evidence, although we hypothesize the participation of neuroendocrine-immune pathways, which have played a relevant role in autoimmune diseases. Cells found in the liver present receptors for several cytokines, hormones, peptides, and neurotransmitters that would allow for system crosstalk. Furthermore, the liver is innervated by the autonomic system and may, thus, be influenced by the parasympathetic and sympathetic systems. This review therefore seeks to discuss classical immunological hepatic tolerance mechanisms and hypothesizes the possible participation of the neuroendocrine-immune system based on the current literature.
MeSH term(s)	Humans ; Immune System ; Immune Tolerance ; Liver ; Liver Transplantation/adverse effects ; Neurosecretory Systems
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152327
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Article: Multiparametric Color Tendency Analysis (MCTA): A Method to Analyze Several Flow Cytometry Labelings Simultaneously.

Henriques-Pons, Andrea / Beatrici, Carine P / Sánchez-Arcila, Juan Camilo / da Silva, Fabricio Alves Barbosa

Frontiers in bioengineering and biotechnology

2020 Volume 8, Page(s) 526814

Abstract: Despite the remarkable evolution of flow cytometers, fluorescent probes, and flow cytometry analysis software, most users still follow the same ways for data analysis. Conventional flow cytometry analysis relies on the creation of dot plot sequences, ... ...

Abstract	Despite the remarkable evolution of flow cytometers, fluorescent probes, and flow cytometry analysis software, most users still follow the same ways for data analysis. Conventional flow cytometry analysis relies on the creation of dot plot sequences, based on two fluorescence parameters at a time, to evidence phenotypically distinct populations. Thus, reaching conclusions about the biological characteristics of the samples is a fragmented and challenging process. We present here the MCTA (Multiparametric Color Tendency Analysis), a method for data analysis that considers multiple labelings simultaneously, extending and complementing conventional analysis. The MCTA method executes the background fluorescence exclusion, spillover compensation, and a user-defined gating strategy for subpopulation analysis. The results are then presented in conventional FSC x SSC dot plots with statistical data. For each event, the method converts each of the multiple fluorescence colors under analysis into a vector, with longer vectors being attributed to more intense labelings. Then, the MCTA generates a resultant vector, which is therefore mostly influenced by predominant labelings. The radial position of this resultant vector corresponds to a resultant color, making it easy to visualize phenotypic modulations among cellular subpopulations. Besides, it is a deterministic method that quickly assigns a resulting color to all events that obey the gating strategy, with no polymeric regions defined by the user or downsampling. The MCTA application generates a single dot plot showing all events in the FCS file, but a resultant color is attributed only to those that obey the gating strategy. Therefore, it can also help to evidence rare events or unpredicted subpopulations naturally excluded from the regions defined by the user. We believe that the MCTA method adds a new perspective over multiparametric flow cytometry analysis while evidencing modulations of molecular labeling profiles based on multiple fluorescences. Availability and implementation: The instructions for the MCTA application is freely available at https://github.com/flowcytometry/MCTA.
Language	English
Publishing date	2020-09-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2020.526814
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Article ; Online: In the presence of Trypanosoma cruzi antigens, activated peripheral T lymphocytes retained in the liver induce a proinflammatory phenotypic and functional shift in intrahepatic T lymphocyte.

Meuser-Batista, Marcelo / Vacani-Martins, Natalia / Cascabulho, Cynthia Machado / Beghini, Daniela Gois / Henriques-Pons, Andrea

Journal of leukocyte biology

2020 Volume 107, Issue 4, Page(s) 695–706

Abstract: In secondary lymphoid organs, pathogen-derived and endogenous danger molecules are recognized by pattern recognition receptors, leading to adaptive proinflammatory immune responses. This conceptual rule does not apply directly to the liver, as hepatic ... ...

Abstract	In secondary lymphoid organs, pathogen-derived and endogenous danger molecules are recognized by pattern recognition receptors, leading to adaptive proinflammatory immune responses. This conceptual rule does not apply directly to the liver, as hepatic immune cells tolerate gut-derived bacterial molecules from the flora. Therefore, the recognition of danger and proinflammatory stimuli differs between the periphery and the liver. However, the tolerant nature of the liver must be overcome in the case of infections or cancer, for example. The central paradigm is the basis for danger recognition and the balance between inflammation and tolerance in the liver. Here, we observed functional integration, with activated peripheral T lymphocytes playing a role in the induction of a proinflammatory environment in the liver in the presence of Trypanosoma cruzi antigens. When only parasite extract was orally administered, it led to the up-regulation of hepatic tolerance markers, but oral treatment plus adoptively transferred activated splenic T lymphocytes led to a proinflammatory response. Moreover, treated/recipient mice showed increased levels of TNF, IFN-γ, IL-6, and CCL2 in the liver and increased numbers of effector and/or effector memory T lymphocytes and F4/80
MeSH term(s)	Adoptive Transfer ; Animals ; Antigens, Protozoan/immunology ; B7-H1 Antigen/metabolism ; CTLA-4 Antigen/metabolism ; Chagas Disease/immunology ; Chagas Disease/parasitology ; Cytokines/metabolism ; Inflammation/pathology ; Intraepithelial Lymphocytes/immunology ; Kupffer Cells/immunology ; Liver/pathology ; Lymphocyte Activation/immunology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Natural Killer T-Cells/immunology ; Parasites/immunology ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/parasitology ; T-Lymphocytes, Regulatory/immunology ; Trypanosoma cruzi/immunology
Chemical Substances	Antigens, Protozoan ; B7-H1 Antigen ; CTLA-4 Antigen ; Cd274 protein, mouse ; Cytokines ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2020-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.3A0220-399RR
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