Annie Riera Leal - Academia.edu (original) (raw)

Papers by Annie Riera Leal

Research paper thumbnail of DNA as a perfect quantum computer based on the quantum physics principle

Research paper thumbnail of DNA as a perfect quantum computer based on the quantum physics principles

Scientific reports, May 21, 2024

DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic ... more DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic multiscale nature requires chemistry and quantum physics to understand the structure and quantum informatics to explain its operation as a perfect quantum computer. Here, we present theoretical results of DNA that allow a better description of its structure and the operation process in the transmission, coding, and decoding of genetic information. Aromaticity is explained by the oscillatory resonant quantum state of correlated electron and hole pairs due to the quantized molecular vibrational energy acting as an attractive force. The correlated pairs form a supercurrent in the nitrogenous bases in a single band π-molecular orbital (π-MO). The MO wave function (�) is assumed to be the linear combination of the n constituent atomic orbitals. The central Hydrogen bond between Adenine (A) and Thymine (T) or Guanine (G) and Cytosine (C) functions like an ideal Josephson Junction. The approach of a Josephson Effect between two superconductors is correctly described, as well as the condensation of the nitrogenous bases to obtain the two entangled quantum states that form the qubit. Combining the quantum state of the composite system with the classical information, RNA polymerase teleports one of the four Bell states. DNA is a perfect quantum computer.

Research paper thumbnail of A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Oncology Reports, Jan 19, 2018

Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinan... more Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

Research paper thumbnail of Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis

Journal of Investigative Dermatology

Research paper thumbnail of LB712 Transcriptomic profiling of Necrobiotic Xanthogranuloma and Necrobiosis Lipoidica provides insight into pathogenic role of T and B cells

Journal of Investigative Dermatology

Innate lymphoid cells type 1 (ILC1) express NKG2D and produce large amounts of IFN-g, i.e. two ke... more Innate lymphoid cells type 1 (ILC1) express NKG2D and produce large amounts of IFN-g, i.e. two key elements in the pathogenesis of alopecia areata (AA). In this study, we aimed to explore a possible involvement of ILC1-like cells in human AA by using ex-vivo and in-vivo models for human AA. Triple immunofluorescence staining of AA sections revealed pathological infiltrates of NKG2D+ ILC1-like cells in and around the anagen hair bulb of lesional AA HFs, but also (more discretely) in/around non-lesional AA HFs, together with a dominant infiltrate of CD8+/ NKG2D+ cells. Next, autologous circulating human ILC1-like cells were expanded and cocultured with organ-cultured, stressed human scalp hair follicles (HFs) ex vivo or injected into healthy human xenotransplants on SCID mice in vivo. Co-culture with ILC1-like cells induced abnormal HLA-DR, HLA-ABC, CD1d and MICA protein expression in the proximal HF epithelium, and down-regulated immunoreactivity for the HF immune privilege (IP) guardians,

Research paper thumbnail of Análisis de la co-expresión del receptor de estrógenos, receptor de prolactina y β-catenina en cáncer cervicouterino y sus lesiones precursoras: efectos del 17β-estradiol y la prolactina en la sobrevida, el metabolismo celular y el perfil de citocinas

Biblioteca Digital wdg.biblio, Jan 30, 2019

Research paper thumbnail of The Clinical Significance of MIF Serum-Level as an Early Predictive Marker of Cardiovascular Risk in Patients with Vitiligo

American Journal of Biomedical Science & Research, 2021

This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001774.

Research paper thumbnail of Immune profiling of lupus miliaris disseminatus faciei and successful management with anti‐tumour necrosis factor therapy

Clinical and Experimental Dermatology, 2021

Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiolo... more Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T‐cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition.

Research paper thumbnail of Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G

Research paper thumbnail of Melanoma nodular hipomelanótico

Hypomelanotic nodular melanoma accounts for up to 8.1% of melanomas and it is identified by the l... more Hypomelanotic nodular melanoma accounts for up to 8.1% of melanomas and it is identified by the lack of pigment. Its clinical polymorphism and the lack of a distinctive dermoscopic pattern have become this neoplasm in a real diagnostic challenge, often associated to misdiagnosis, delays in the treatment and leading to a poor prognosis of the patients. We describe dermoscopic features in two lesions, diagnosed as hypomelanotic nodular melanoma on biopsy, comparing our findings with those reported by other authors.

Research paper thumbnail of Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications

Research paper thumbnail of Nanobodies as efficient drug-carriers: Progress and trends in chemotherapy

Journal of Controlled Release

Research paper thumbnail of B7-H6, an immunoligand for the natural killer cell activating receptor NKp30, reveals inhibitory effects on cell proliferation and migration, but not apoptosis, in cervical cancer derived-cell lines

BMC Cancer

Background Although great progress has been made in treatment regimens, cervical cancer remains a... more Background Although great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored. Methods In this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 w...

Research paper thumbnail of Osteonecrosis of the calvarium: When clear margins are an impractical goal

Research paper thumbnail of Macrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non‐segmental vitiligo in patients from western Mexico

Molecular Genetics & Genomic Medicine

Research paper thumbnail of Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

Oncology Reports

Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin recept... more Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin receptor (PRLR) have been reported to be involved in the physiopathology of uterine cervical cancer (UCC). The 60 kDa PRL is an isoform of PRL, which is produced by UCC-derived cells. The present study aimed to evaluate the expression of hormonal receptors in different degrees of cervical lesions, and to determine whether 60 kDa PRL and 17β-estradiol (E2) modulated cell survival and metabolism in UCC cells, and in HaCaT cells transduced with human papillomavirus (HPV) 16 and 18 E6/E7 oncogenes. ERα, ERβ, PRLR, Ki67 and B-cell lymphoma 2 expression levels were analyzed in biopsies of precursor lesions and UCC using immunohistochemistry. In addition, HeLa, SiHa and C33A cells, and transduced HaCaT cells, were stimulated with 60 kDa PRL, E2 or a combination of both. Proliferation was evaluated using the xCELLigence platform, apoptosis was analyzed by flow cytometry and cell metabolism was determined using the MTT assay. The results revealed that ERα, ERβ, PRLR and Ki67 expression levels were increased during the progression of cancer. In vitro, 60 kDa PRL alone significantly increased proliferation of SiHa cells. Furthermore, E2 alone or in combination with 60 kDa PRL increased the sensitivity of SiHa cells to cisplatin and increased the percentage of apoptosis; in HaCaT cells, these treatment strategies had the opposite effect on cisplatin sensitivity. Treatment with E2 increased mitochondrial activity in HeLa and SiHa cells, and in HaCaT cells transduced with HPV 16 E6/E7 and HPV 18 E6 oncogenes. PRL had a similar effect on HeLa cells, and on HaCaT cells transduced with HPV 18 E6 and HPV 16 E7. The co-expression of these receptors demonstrated the hormonal dependence of UCC. In addition, E2 and the 60 kDa PRL significantly impacted the metabolism, but not the survival, of cells.

Research paper thumbnail of 17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress

International Journal of Oncology

Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell pr... more Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell proliferation. The mechanistic understanding of estrogen in cervical cancer is poorly understood. Therefore, the objective of this study was to determine how 17β-estradiol (E2) affects mitochondrial function and the Warburg effect in SiHa, HeLa and C33A cervical cancer cells. Mitochondrial compromise was evaluated measuring changes in the membrane permeability by immunofluorescence, calcium concentration, redox status, iron and ferritin reserves. Glucose consumption and lactic acid assays were used to detect the metabolic activity. Results were confirmed at molecular level by analysis of the differential gene expression using RNA sequencing. E2 modified the mitochondrial permeability and produced an alteration in the calcium signaling pathway. In HeLa and SiHa, there was a significant decrease in nitric oxide levels and lipid peroxidation, and an increase in glucose consumption and lactic acid levels when stimulated with E2. Intracellular iron or ferritin reserves were not affected by the E2 treatment. Genes differentially modulated by E2 were involved in the mitochondrial electron transport chain, oxidative phosphorylation system, glycolysis, pentose phosphate pathway and the regulation of metabolic signaling pathways. Herein, we provide evidence for a primary effect of estrogen on mitochondrial function and the Warburg effect, favoring the metabolic adaptation of the cervical cancer cell lines and their survival.

Research paper thumbnail of Microbiota and Its Role on Viral Evasion: Is It With Us or Against Us?

Frontiers in Cellular and Infection Microbiology

Research paper thumbnail of A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Oncology Reports

Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinan... more Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

Research paper thumbnail of Immune Response in Gingival Disease: Role of Macrophage Migration Inhibitory Factor

Gingival Disease - A Comprehensive and Professional Approach for Treatment and Prevention [Working Title]

The term periodontal disease encompasses a wide variety of chronic inflammatory conditions of the... more The term periodontal disease encompasses a wide variety of chronic inflammatory conditions of the periodontium, including gingivitis and periodontitis. The gingival disease is an infectious process, which occurs due to the progression of untreated gingivitis. It is characterized by a destructive inflammatory process that affects the supporting tissues of the teeth, which causes the loss of the dental organs. As a result of inflammation, a wide range of cytokines and inflammatory mediators together contribute to tissue degradation and bone resorption. However, some molecules that have not been studied in the inflammatory process of this disease, such as the macrophage migration inhibitory factor (MIF) which is considered an important cytokine of the innate immune system; it is expressed constitutively in immune and nonimmune cells, and it is released immediately against bacterial stimuli, hypoxia, and proliferative signals. MIF has been described in some chronic degenerative, inflammatory, and autoimmune diseases. Previous studies have described that in murine models of periodontitis, MIF promotes the activation and differentiation of osteoclasts that could position this cytokine in the immunopathogenesis of gingival disease in humans.

Research paper thumbnail of DNA as a perfect quantum computer based on the quantum physics principle

Research paper thumbnail of DNA as a perfect quantum computer based on the quantum physics principles

Scientific reports, May 21, 2024

DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic ... more DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic multiscale nature requires chemistry and quantum physics to understand the structure and quantum informatics to explain its operation as a perfect quantum computer. Here, we present theoretical results of DNA that allow a better description of its structure and the operation process in the transmission, coding, and decoding of genetic information. Aromaticity is explained by the oscillatory resonant quantum state of correlated electron and hole pairs due to the quantized molecular vibrational energy acting as an attractive force. The correlated pairs form a supercurrent in the nitrogenous bases in a single band π-molecular orbital (π-MO). The MO wave function (�) is assumed to be the linear combination of the n constituent atomic orbitals. The central Hydrogen bond between Adenine (A) and Thymine (T) or Guanine (G) and Cytosine (C) functions like an ideal Josephson Junction. The approach of a Josephson Effect between two superconductors is correctly described, as well as the condensation of the nitrogenous bases to obtain the two entangled quantum states that form the qubit. Combining the quantum state of the composite system with the classical information, RNA polymerase teleports one of the four Bell states. DNA is a perfect quantum computer.

Research paper thumbnail of A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Oncology Reports, Jan 19, 2018

Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinan... more Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

Research paper thumbnail of Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis

Journal of Investigative Dermatology

Research paper thumbnail of LB712 Transcriptomic profiling of Necrobiotic Xanthogranuloma and Necrobiosis Lipoidica provides insight into pathogenic role of T and B cells

Journal of Investigative Dermatology

Innate lymphoid cells type 1 (ILC1) express NKG2D and produce large amounts of IFN-g, i.e. two ke... more Innate lymphoid cells type 1 (ILC1) express NKG2D and produce large amounts of IFN-g, i.e. two key elements in the pathogenesis of alopecia areata (AA). In this study, we aimed to explore a possible involvement of ILC1-like cells in human AA by using ex-vivo and in-vivo models for human AA. Triple immunofluorescence staining of AA sections revealed pathological infiltrates of NKG2D+ ILC1-like cells in and around the anagen hair bulb of lesional AA HFs, but also (more discretely) in/around non-lesional AA HFs, together with a dominant infiltrate of CD8+/ NKG2D+ cells. Next, autologous circulating human ILC1-like cells were expanded and cocultured with organ-cultured, stressed human scalp hair follicles (HFs) ex vivo or injected into healthy human xenotransplants on SCID mice in vivo. Co-culture with ILC1-like cells induced abnormal HLA-DR, HLA-ABC, CD1d and MICA protein expression in the proximal HF epithelium, and down-regulated immunoreactivity for the HF immune privilege (IP) guardians,

Research paper thumbnail of Análisis de la co-expresión del receptor de estrógenos, receptor de prolactina y β-catenina en cáncer cervicouterino y sus lesiones precursoras: efectos del 17β-estradiol y la prolactina en la sobrevida, el metabolismo celular y el perfil de citocinas

Biblioteca Digital wdg.biblio, Jan 30, 2019

Research paper thumbnail of The Clinical Significance of MIF Serum-Level as an Early Predictive Marker of Cardiovascular Risk in Patients with Vitiligo

American Journal of Biomedical Science & Research, 2021

This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001774.

Research paper thumbnail of Immune profiling of lupus miliaris disseminatus faciei and successful management with anti‐tumour necrosis factor therapy

Clinical and Experimental Dermatology, 2021

Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiolo... more Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T‐cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition.

Research paper thumbnail of Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G

Research paper thumbnail of Melanoma nodular hipomelanótico

Hypomelanotic nodular melanoma accounts for up to 8.1% of melanomas and it is identified by the l... more Hypomelanotic nodular melanoma accounts for up to 8.1% of melanomas and it is identified by the lack of pigment. Its clinical polymorphism and the lack of a distinctive dermoscopic pattern have become this neoplasm in a real diagnostic challenge, often associated to misdiagnosis, delays in the treatment and leading to a poor prognosis of the patients. We describe dermoscopic features in two lesions, diagnosed as hypomelanotic nodular melanoma on biopsy, comparing our findings with those reported by other authors.

Research paper thumbnail of Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications

Research paper thumbnail of Nanobodies as efficient drug-carriers: Progress and trends in chemotherapy

Journal of Controlled Release

Research paper thumbnail of B7-H6, an immunoligand for the natural killer cell activating receptor NKp30, reveals inhibitory effects on cell proliferation and migration, but not apoptosis, in cervical cancer derived-cell lines

BMC Cancer

Background Although great progress has been made in treatment regimens, cervical cancer remains a... more Background Although great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored. Methods In this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 w...

Research paper thumbnail of Osteonecrosis of the calvarium: When clear margins are an impractical goal

Research paper thumbnail of Macrophage inhibitory factor (MIF) gene polymorphisms are associated with disease susceptibility and with circulating MIF levels in active non‐segmental vitiligo in patients from western Mexico

Molecular Genetics & Genomic Medicine

Research paper thumbnail of Effects of 60�kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co‑expression of their hormonal receptors during cancer progression

Oncology Reports

Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin recept... more Estrogens and estrogen receptors (ERs), such as ERα and ERβ, prolactin (PRL) and prolactin receptor (PRLR) have been reported to be involved in the physiopathology of uterine cervical cancer (UCC). The 60 kDa PRL is an isoform of PRL, which is produced by UCC-derived cells. The present study aimed to evaluate the expression of hormonal receptors in different degrees of cervical lesions, and to determine whether 60 kDa PRL and 17β-estradiol (E2) modulated cell survival and metabolism in UCC cells, and in HaCaT cells transduced with human papillomavirus (HPV) 16 and 18 E6/E7 oncogenes. ERα, ERβ, PRLR, Ki67 and B-cell lymphoma 2 expression levels were analyzed in biopsies of precursor lesions and UCC using immunohistochemistry. In addition, HeLa, SiHa and C33A cells, and transduced HaCaT cells, were stimulated with 60 kDa PRL, E2 or a combination of both. Proliferation was evaluated using the xCELLigence platform, apoptosis was analyzed by flow cytometry and cell metabolism was determined using the MTT assay. The results revealed that ERα, ERβ, PRLR and Ki67 expression levels were increased during the progression of cancer. In vitro, 60 kDa PRL alone significantly increased proliferation of SiHa cells. Furthermore, E2 alone or in combination with 60 kDa PRL increased the sensitivity of SiHa cells to cisplatin and increased the percentage of apoptosis; in HaCaT cells, these treatment strategies had the opposite effect on cisplatin sensitivity. Treatment with E2 increased mitochondrial activity in HeLa and SiHa cells, and in HaCaT cells transduced with HPV 16 E6/E7 and HPV 18 E6 oncogenes. PRL had a similar effect on HeLa cells, and on HaCaT cells transduced with HPV 18 E6 and HPV 16 E7. The co-expression of these receptors demonstrated the hormonal dependence of UCC. In addition, E2 and the 60 kDa PRL significantly impacted the metabolism, but not the survival, of cells.

Research paper thumbnail of 17β‑estradiol‑induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress

International Journal of Oncology

Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell pr... more Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell proliferation. The mechanistic understanding of estrogen in cervical cancer is poorly understood. Therefore, the objective of this study was to determine how 17β-estradiol (E2) affects mitochondrial function and the Warburg effect in SiHa, HeLa and C33A cervical cancer cells. Mitochondrial compromise was evaluated measuring changes in the membrane permeability by immunofluorescence, calcium concentration, redox status, iron and ferritin reserves. Glucose consumption and lactic acid assays were used to detect the metabolic activity. Results were confirmed at molecular level by analysis of the differential gene expression using RNA sequencing. E2 modified the mitochondrial permeability and produced an alteration in the calcium signaling pathway. In HeLa and SiHa, there was a significant decrease in nitric oxide levels and lipid peroxidation, and an increase in glucose consumption and lactic acid levels when stimulated with E2. Intracellular iron or ferritin reserves were not affected by the E2 treatment. Genes differentially modulated by E2 were involved in the mitochondrial electron transport chain, oxidative phosphorylation system, glycolysis, pentose phosphate pathway and the regulation of metabolic signaling pathways. Herein, we provide evidence for a primary effect of estrogen on mitochondrial function and the Warburg effect, favoring the metabolic adaptation of the cervical cancer cell lines and their survival.

Research paper thumbnail of Microbiota and Its Role on Viral Evasion: Is It With Us or Against Us?

Frontiers in Cellular and Infection Microbiology

Research paper thumbnail of A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production

Oncology Reports

Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinan... more Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1β and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1β and TNF-α production by THP-1 macrophages.

Research paper thumbnail of Immune Response in Gingival Disease: Role of Macrophage Migration Inhibitory Factor

Gingival Disease - A Comprehensive and Professional Approach for Treatment and Prevention [Working Title]

The term periodontal disease encompasses a wide variety of chronic inflammatory conditions of the... more The term periodontal disease encompasses a wide variety of chronic inflammatory conditions of the periodontium, including gingivitis and periodontitis. The gingival disease is an infectious process, which occurs due to the progression of untreated gingivitis. It is characterized by a destructive inflammatory process that affects the supporting tissues of the teeth, which causes the loss of the dental organs. As a result of inflammation, a wide range of cytokines and inflammatory mediators together contribute to tissue degradation and bone resorption. However, some molecules that have not been studied in the inflammatory process of this disease, such as the macrophage migration inhibitory factor (MIF) which is considered an important cytokine of the innate immune system; it is expressed constitutively in immune and nonimmune cells, and it is released immediately against bacterial stimuli, hypoxia, and proliferative signals. MIF has been described in some chronic degenerative, inflammatory, and autoimmune diseases. Previous studies have described that in murine models of periodontitis, MIF promotes the activation and differentiation of osteoclasts that could position this cytokine in the immunopathogenesis of gingival disease in humans.