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Article ; Online: Bactericidal Permeability-Increasing Protein (BPI) Inhibits

Guzmán-Beltrán, Silvia / Juárez, Esmeralda / Cruz-Muñoz, Brenda L / Páez-Cisneros, Cesar A / Sarabia, Carmen / González, Yolanda

Biomolecules

2024 Volume 14, Issue 4

Abstract: Bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils, eosinophils, fibroblasts, and macrophages with antibacterial anti-inflammatory properties. In the context of Gram-negative infection, BPI ... ...

Abstract	Bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils, eosinophils, fibroblasts, and macrophages with antibacterial anti-inflammatory properties. In the context of Gram-negative infection, BPI kills bacteria, neutralizes the endotoxic activity of lipopolysaccharides (LPSs), and, thus, avoids immune hyperactivation. Interestingly, BPI increases in patients with Gram-positive meningitis, interacts with lipopeptides and lipoteichoic acids of Gram-positive bacteria, and significantly enhances the immune response in peripheral blood mononuclear cells. We evaluated the antimycobacterial and immunoregulatory properties of BPI in human macrophages infected with
MeSH term(s)	Humans ; Mycobacterium tuberculosis/growth & development ; Mycobacterium tuberculosis/drug effects ; Blood Proteins/metabolism ; Blood Proteins/pharmacology ; Macrophages/metabolism ; Macrophages/immunology ; Macrophages/drug effects ; Macrophages/microbiology ; Antimicrobial Cationic Peptides/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Tuberculosis/microbiology ; Tuberculosis/immunology ; Tuberculosis/drug therapy
Chemical Substances	bactericidal permeability increasing protein ; Blood Proteins ; Antimicrobial Cationic Peptides ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2024-04-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14040475
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Flavivirus vaccines: Virus-like particles and single-round infectious particles as promising alternatives.

Cuevas-Juárez, Esmeralda / Pando-Robles, Victoria / Palomares, Laura A

Vaccine

2021 Volume 39, Issue 48, Page(s) 6990–7000

Abstract: The genus flavivirus of the Flaviridae family includes several human pathogens, like dengue, Zika, Japanese encephalitis, and yellow fever virus. These viruses continue to be a significant threat to human health. Vaccination remains the most useful ... ...

Abstract	The genus flavivirus of the Flaviridae family includes several human pathogens, like dengue, Zika, Japanese encephalitis, and yellow fever virus. These viruses continue to be a significant threat to human health. Vaccination remains the most useful approach to reduce the impact of flavivirus fever. However, currently available vaccines can induce severe side effects or have low effectiveness. An alternative is the use of recombinant vaccines, of which virus-like particles (VLP) and single-round infectious particles (SRIP) are of especial interest. VLP consist of the virus structural proteins produced in a heterologous system that self-assemble in a structure almost identical to the native virus. They are highly immunogenic and have been effective vaccines for other viruses for over 30 years. SRIP are promising vaccine candidates, as they induce both cellular and humoral responses, as viral proteins are expressed. Here, the state of the art to produce both types of particles and their use as vaccines against flaviviruses are discussed. We summarize the different approaches used for the design and production of flavivirus VLP and SRIP, the evidence for their safety and efficacy, and the main challenges for their use as commercial vaccines.
MeSH term(s)	Flavivirus ; Humans ; Vaccines, Synthetic ; Viral Vaccines ; Yellow fever virus ; Zika Virus ; Zika Virus Infection/prevention & control
Chemical Substances	Vaccines, Synthetic ; Viral Vaccines
Language	English
Publishing date	2021-11-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2021.10.049
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Article ; Online: Effect of sericin, a silk derived protein, on the amplification of Zika virus in insect and mammalian cell cultures.

Alcalá, Ana C / Contreras, Martha A / Cuevas-Juárez, Esmeralda / Ramírez, Octavio T / Palomares, Laura A

Journal of biotechnology

2022 Volume 353, Page(s) 28–35

Abstract: Sericin, a silk-derived non-immunogenic protein, has been used to improve cell culture performance by increasing viability, cell concentration, and promoting adherence of several cell lines. Here, we hypothesized that the properties of sericin can ... ...

Abstract	Sericin, a silk-derived non-immunogenic protein, has been used to improve cell culture performance by increasing viability, cell concentration, and promoting adherence of several cell lines. Here, we hypothesized that the properties of sericin can enhance the amplification of flaviviruses in cell cultures. The propagation of flavivirus is inefficient and limits scientific research. Zika virus (ZIKV) is an important human pathogen that has been widely studied because of its high impact on public health. There is a need to amplify Zika virus both for research and vaccine development. In this work, we show that sericin improves ZIKV amplification in insect (C6/36) and mammalian (Vero) cell cultures, and that it has a cryoprotectant capacity. Supplementation of cell culture media with sericin at 80 µg/mL resulted in a significant increase of 1 log in the concentration of ZIKV infectious particles produced from both cell lines. Furthermore, final virus yields increased between 5 and 10-fold in Vero cells and between 7 and 23-fold in C6/36 cells when sericin was supplemented, compared to control conditions. These results show that sericin is an effective supplement to increase ZIKV production by Vero and C6/36 cells. Additionally, sericin was a suitable cryoprotective agent, and hence an alternative to FBS and DMSO, for the cryopreservation of C6/36 cells but not for Vero cells.
MeSH term(s)	Animals ; Cell Culture Techniques/methods ; Chlorocebus aethiops ; Humans ; Insecta ; Mammals ; Sericins/metabolism ; Sericins/pharmacology ; Silk/metabolism ; Vero Cells ; Zika Virus ; Zika Virus Infection/drug therapy
Chemical Substances	Sericins ; Silk
Language	English
Publishing date	2022-05-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	843647-2
ISSN	1873-4863 ; 0168-1656 ; 1389-0352
ISSN (online)	1873-4863
ISSN	0168-1656 ; 1389-0352
DOI	10.1016/j.jbiotec.2022.05.005
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Zs.A 2299: Show issues

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Article ; Online: Mimotope discovery as a tool to design a vaccine against Zika and dengue viruses.

Cuevas-Juárez, Esmeralda / Liñan-Torres, Arturo / Hernández, Carolina / Kopylov, Mykhailo / Potter, Clint S / Carragher, Bridget / Ramírez, Octavio T / Palomares, Laura A

Biotechnology and bioengineering

2023 Volume 120, Issue 9, Page(s) 2658–2671

Abstract: Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ... ...

Abstract	Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ADE. Current vaccines and vaccine candidates contain the complete envelope viral protein, with epitopes that can raise antibodies causing ADE. We used the envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses. However, EDE is a discontinuous quaternary epitope that cannot be isolated from the E protein without other epitopes. Utilizing phage display, we selected three peptides that mimic the EDE. Free mimotopes were disordered and did not elicit an immune response. After their display on adeno-associated virus (AAV) capsids (VLP), they recovered their structure and were recognized by an EDE-specific antibody. Characterization by cryo-EM and enzyme-linked immunosorbent assay confirmed the correct display of a mimotope on the surface of the AAV VLP and its recognition by the specific antibody. Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV. This work provides the basis for developing a Zika and dengue virus vaccine candidate that will not induce ADE.
MeSH term(s)	Humans ; Zika Virus ; Zika Virus Infection/prevention & control ; Dengue Virus/chemistry ; Dengue/prevention & control ; Antibodies, Viral ; Viral Envelope Proteins/chemistry ; Antibodies, Neutralizing ; Vaccines ; Epitopes ; Cross Reactions
Chemical Substances	Antibodies, Viral ; Viral Envelope Proteins ; Antibodies, Neutralizing ; Vaccines ; Epitopes
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280318-5
ISSN	1097-0290 ; 0006-3592
ISSN (online)	1097-0290
ISSN	0006-3592
DOI	10.1002/bit.28392
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Article ; Online: Resolvin D1 (RvD1) and maresin 1 (Mar1) contribute to human macrophage control of M. tuberculosis infection while resolving inflammation.

Ruiz, Andy / Sarabia, Carmen / Torres, Martha / Juárez, Esmeralda

International immunopharmacology

2019 Volume 74, Page(s) 105694

Abstract: Resolvins and protectins counter inflammation, enhance phagocytosis, induce bactericidal/permeability-increasing protein (BPI) expression, and restore inflamed tissue to homeostasis. Because modulating the inflammation/antiinflammation balance is ... ...

Abstract	Resolvins and protectins counter inflammation, enhance phagocytosis, induce bactericidal/permeability-increasing protein (BPI) expression, and restore inflamed tissue to homeostasis. Because modulating the inflammation/antiinflammation balance is important in Mycobacterium tuberculosis infection, we evaluated the effects of resolvins and protectins on human macrophages infected in vitro. Monocyte-derived macrophages were infected with M. tuberculosis H37Rv at a multiplicity of infection (MOI) of 5 and treated 1 h post-infection in vitro with 100 nM LXA4, RvD1, RvD2, PD1 or 150 nM Mar1. After 24 h, cytokine production was measured by Luminex, and BPI and cathelicidin LL37 expression was determined by real-time PCR. Macrophage bactericidal activity was assessed by colony-forming units (CFUs) 3 days posttreatment. Nuclear translocation of Nrf2 was assessed by ELISA, NFκB translocation was determined by imaging cytometry, and BPI production was determined by fluorescence microscopy. We found that all lipids reduced LPS-dependent and M. tuberculosis-induced TNF-α production. RvD1 and Mar1 also induced a significant reduction in M. tuberculosis intracellular growth. RvD1 and Mar1 elicited distinct immunomodulatory patterns. RvD1 induced upregulation of both antimicrobial effector genes (BPI and LL37) and cytokines (GM-CSF and IL-6). Mar1 induced only BPI overexpression. RvD1 and Mar1 induced NFκB nuclear translocation, but only Mar1 induced Nrf2 translocation. Inhibition of G protein-coupled receptor signaling in infected macrophages abrogated the regulatory effects of RvD1. In conclusion, RvD1 and Mar1 modulate the anti-inflammatory and antimicrobial properties of M. tuberculosis-infected human macrophages. Since both proresolving lipids are inducible and synthesized from dietary components, they have immunotherapeutic potential against tuberculosis when inflammation is uncontrolled.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Antimicrobial Cationic Peptides/genetics ; Antimicrobial Cationic Peptides/metabolism ; Blood Proteins/genetics ; Blood Proteins/metabolism ; Cell Growth Processes ; Cells, Cultured ; Docosahexaenoic Acids/pharmacology ; Humans ; Immunomodulation ; Inflammation/immunology ; Inflammation/therapy ; Macrophages/immunology ; Mycobacterium tuberculosis/physiology ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Phagocytosis ; Tuberculosis/immunology ; Tuberculosis/therapy ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid ; Anti-Inflammatory Agents ; Antimicrobial Cationic Peptides ; Blood Proteins ; NF-E2-Related Factor 2 ; NF-kappa B ; NFE2L2 protein, human ; Tumor Necrosis Factor-alpha ; bactericidal permeability increasing protein ; resolvin D1 ; Docosahexaenoic Acids (25167-62-8) ; ropocamptide (3DD771JO2H)
Language	English
Publishing date	2019-06-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2019.105694
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Zs.A 5408: Show issues

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Article: Effect of sericin, a silk derived protein, on the amplification of Zika virus in insect and mammalian cell cultures

Alcalá, Ana C. / Contreras, Martha A. / Cuevas-Juárez, Esmeralda / Ramírez, Octavio T. / Palomares, Laura A.

Journal of biotechnology. 2022 May 13,

2022

Abstract	Sericin, a silk-derived non-immunogenic protein, has been used to improve cell culture performance by increasing viability, cell concentration, and promoting adherence of several cell lines. Here, we hypothesized that the properties of sericin can enhance the amplification of flaviviruses in cell cultures. The propagation of flavivirus is inefficient and limits scientific research. Zika virus (ZIKV) is an important human pathogen that has been widely studied because of its high impact on public health. There is a need to amplify Zika virus both for research and vaccine development. In this work, we show that sericin improves ZIKV amplification in insect (C6/36) and mammalian (VeroE6) cell cultures, and that it has a cryoprotectant capacity. Supplementation of cell culture media with sericin at 80µg/mL resulted in a significant increase of 1log in the concentration of ZIKV infectious particles produced from both cell lines. Furthermore, final virus yields increased between 5 to 10-fold in Vero cells and between 7 to 23-fold in C6/36 cells when sericin was supplemented, compared to control conditions. These results show that sericin is an effective supplement to increase ZIKV production by Vero and C6/36 cells. Additionally, sericin was a suitable cryoprotective agent, and hence an alternative to FBS and DMSO, for the cryopreservation of C6/36 cells but not for Vero cells.
Keywords	Zika virus ; animal pathogens ; biotechnology ; cell culture ; cryopreservation ; cryoprotectants ; insects ; mammals ; public health ; sericin ; silk ; vaccine development ; viability ; viruses
Language	English
Dates of publication	2022-0513
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	843647-2
ISSN	1873-4863 ; 0168-1656 ; 1389-0352
ISSN (online)	1873-4863
ISSN	0168-1656 ; 1389-0352
DOI	10.1016/j.jbiotec.2022.05.005
Database	NAL-Catalogue (AGRICOLA)

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Article: Flavivirus vaccines: Virus-like particles and single-round infectious particles as promising alternatives

Cuevas-Juárez, Esmeralda / Pando-Robles, Victoria / Palomares, Laura A.

Vaccine. 2021 Nov. 26, v. 39, no. 48

2021

Abstract	The genus flavivirus of the Flaviridae family includes several human pathogens, like dengue, Zika, Japanese encephalitis, and yellow fever virus. These viruses continue to be a significant threat to human health. Vaccination remains the most useful approach to reduce the impact of flavivirus fever. However, currently available vaccines can induce severe side effects or have low effectiveness. An alternative is the use of recombinant vaccines, of which virus-like particles (VLP) and single-round infectious particles (SRIP) are of especial interest. VLP consist of the virus structural proteins produced in a heterologous system that self-assemble in a structure almost identical to the native virus. They are highly immunogenic and have been effective vaccines for other viruses for over 30 years. SRIP are promising vaccine candidates, as they induce both cellular and humoral responses, as viral proteins are expressed. Here, the state of the art to produce both types of particles and their use as vaccines against flaviviruses are discussed. We summarize the different approaches used for the design and production of flavivirus VLP and SRIP, the evidence for their safety and efficacy, and the main challenges for their use as commercial vaccines.
Keywords	Yellow fever virus ; dengue ; encephalitis ; fever ; human health ; humans ; vaccination ; viruses
Language	English
Dates of publication	2021-1126
Size	p. 6990-7000.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2021.10.049
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: High Vitamin D Concentrations Restore the Ability to Express LL37 by

Herrera, María Teresa / Juárez, Esmeralda / Guzmán-Beltrán, Silvia / Torres, Martha / Luna-Morales, Victor Adrián / Villalana-Alvarez, Leonardo Daniel / González, Yolanda

Biomolecules

2022 Volume 12, Issue 2

Abstract: Vitamin D has an immunomodulatory function and is involved in eliminating pathogens. Vitamin D deficiencies reported in Type 2 diabetes mellitus (T2DM) patients make them more susceptible to developing tuberculosis (TB). The macrophages are the immune ... ...

Abstract	Vitamin D has an immunomodulatory function and is involved in eliminating pathogens. Vitamin D deficiencies reported in Type 2 diabetes mellitus (T2DM) patients make them more susceptible to developing tuberculosis (TB). The macrophages are the immune cells that control intracellular pathogens by producing the antimicrobial peptide cathelicidin-LL37. This pathway involves TLR activation by pathogens, vitamin D receptor (VDR) ligation, and the enzyme 1α-hydroxylase Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). However, it is not clear whether the biological actions of vitamin D are affected by high glucose concentrations. This study aimed to evaluate the vitamin D contribution in the expression of VDR and CYP27B1, involved in the conversion of an inactive to an active form of vitamin D in the infected macrophages using
MeSH term(s)	25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Diabetes Mellitus, Type 2 ; Humans ; Macrophages/metabolism ; Vitamin D/pharmacology ; Vitamins
Chemical Substances	Vitamins ; Vitamin D (1406-16-2) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18)
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12020268
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Article ; Online: Sex-Dependent Differential Expression of Lipidic Mediators Associated with Inflammation Resolution in Patients with Pulmonary Tuberculosis.

Carranza, Claudia / Carreto-Binaghi, Laura Elena / Guzmán-Beltrán, Silvia / Muñoz-Torrico, Marcela / Torres, Martha / González, Yolanda / Juárez, Esmeralda

Biomolecules

2022 Volume 12, Issue 4

Abstract: There is a sex bias in tuberculosis's severity, prevalence, and pathogenesis, and the rates are higher in men. Immunological and physiological factors are fundamental contributors to the development of the disease, and sex-related factors could play an ... ...

Abstract	There is a sex bias in tuberculosis's severity, prevalence, and pathogenesis, and the rates are higher in men. Immunological and physiological factors are fundamental contributors to the development of the disease, and sex-related factors could play an essential role in making women more resistant to severe forms of the disease. In this study, we evaluated sex-dependent differences in inflammatory markers. Serum samples were collected from 34 patients diagnosed with pulmonary TB (19 male and 15 female) and 27 healthy controls (18 male and 9 female). Cytokines IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα, and GM-CSF, and eicosanoids PGE2, LTB4, RvD1, and Mar1 were measured using commercially available immunoassays. The MDA, a product of lipidic peroxidation, was measured by detecting thiobarbituric-acid-reactive substances (TBARS). Differential inflammation patterns between men and women were observed. Men had higher levels of IL6, IL8, and TNFα than women. PGE2 and LTB4 levels were higher in patients than healthy controls, but there were no differences for RvD1 and Mar1. Women had higher RvD1/PGE2 and RvD1/LTB4 ratios among patients. RvD1 plays a vital role in resolving the inflammatory process of TB in women. Men are the major contributors to the typical pro-inflammatory profile observed in the serum of tuberculosis patients.
MeSH term(s)	Dinoprostone ; Eicosanoids ; Female ; Humans ; Inflammation/complications ; Interleukin-6 ; Interleukin-8 ; Leukotriene B4 ; Male ; Tuberculosis/complications ; Tuberculosis, Pulmonary/complications ; Tumor Necrosis Factor-alpha
Chemical Substances	Eicosanoids ; Interleukin-6 ; Interleukin-8 ; Tumor Necrosis Factor-alpha ; Leukotriene B4 (1HGW4DR56D) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2022-03-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12040490
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Article: Reduced IL-8 Secretion by NOD-like and Toll-like Receptors in Blood Cells from COVID-19 Patients.

Carreto-Binaghi, Laura E / Herrera, María Teresa / Guzmán-Beltrán, Silvia / Juárez, Esmeralda / Sarabia, Carmen / Salgado-Cantú, Manuel G / Juarez-Carmona, Daniel / Guadarrama-Pérez, Cristóbal / González, Yolanda

Biomedicines

2023 Volume 11, Issue 4

Abstract: Severe inflammatory responses are associated with the misbalance of innate and adaptive immunity. TLRs, NLRs, and cytokine receptors play an important role in pathogen sensing and intracellular control, which remains unclear in COVID-19. This study aimed ...

Abstract	Severe inflammatory responses are associated with the misbalance of innate and adaptive immunity. TLRs, NLRs, and cytokine receptors play an important role in pathogen sensing and intracellular control, which remains unclear in COVID-19. This study aimed to evaluate IL-8 production in blood cells from COVID-19 patients in a two-week follow-up evaluation. Blood samples were taken at admission (t1) and after 14 days of hospitalization (t2). The functionality of TLR2, TLR4, TLR7/8, TLR9, NOD1, and NOD2 innate receptors and IL-12 and IFN-γ cytokine receptors was evaluated by whole blood stimulation with specific synthetic receptor agonists through the quantification of IL-8, TNF-α, or IFN-γ. At admission, ligand-dependent IL-8 secretion was 6.4, 13, and 2.5 times lower for TLR2, TLR4, and endosomal TLR7/8 receptors, respectively, in patients than in healthy controls. Additionally, IL-12 receptor-induced IFN-γ secretion was lower in COVID-19 patients than in healthy subjects. We evaluated the same parameters after 14 days and observed significantly higher responses for TLR2, TLR4, TLR7/8, TLR9, and NOD1, NOD2, and IFN-γ receptors. In conclusion, the low secretion of IL-8 through stimulation with agonists of TLR2, TLR4, TLR7/8, TLR9, and NOD2 at t1 suggests their possible contribution to immunosuppression following hyperinflammation in COVID-19 disease.
Language	English
Publishing date	2023-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11041078
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