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1.
FEMS Microbiol Lett ; 3712024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38794890

RESUMEN

The COVID-19 pandemic has posed challenges for education, particularly in undergraduate teaching. In this study, we report on the experience of how a private university successfully addressed this challenge through an active methodology applied to a microbiology discipline offered remotely to students from various health-related courses (veterinary, physiotherapy, nursing, biomedicine, and nutrition). Remote teaching was combined with the "Adopt a Bacterium" methodology, implemented for the first time on Google Sites. The distance learning activity notably improved student participation in microbiology discussions, both through word cloud analysis and the richness of discourse measured by the Shannon index. Furthermore, feedback from students about the e-learning approach was highly positive, indicating its effectiveness in motivating and involving students in the learning process. The results also demonstrate that despite being offered simultaneously to students, the methodology allowed for the acquisition of specialized knowledge within each course and sparked student interest in various aspects of microbiology. In conclusion, the remote "Adopt a Bacterium" methodology facilitated knowledge sharing among undergraduate students from different health-related courses and represented a valuable resource in distance microbiology education.


Asunto(s)
COVID-19 , Educación a Distancia , Microbiología , Educación a Distancia/métodos , Microbiología/educación , Humanos , Universidades , SARS-CoV-2 , Estudiantes , Pandemias , Instrucción por Computador/métodos
2.
Animals (Basel) ; 14(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338031

RESUMEN

Probiotics are increasingly recognized for their potential in managing bacterial challenges in animal production. This study aimed to evaluate the probiotic potential of Bacillus and Streptomyces strains, specifically their bioprotective ability against Salmonella. In agar inhibition assays, these bacteria supported Salmonella-inhibition zones, ranging from 2.5 ± 0.5 to 6.3 ± 2.0 mm. Analyses of antimicrobial metabolites revealed their capacity to produce compounds with anti-Salmonella properties, except for Bacillus subtilis MLB2. When Salmonella was exposed to lyophilized metabolites, inhibition occurred in both liquid (at concentrations between 250 and 500 g/L) and solid cultures (at 500 g/L). To confirm their probiotic potential, the S. griseus and Bacillus strains underwent evaluations for antimicrobial resistance, bile salt tolerance, auto- and co-aggregation, pH resistance, and their ability to adhere to and inhibit Salmonella in Caco-2 cells. These assessments confirmed their probiotic potential. The probiotic strains were further encapsulated and subjected to simulated swine and poultry digestion. They demonstrated survival potential through the gastrointestinal tract and significantly reduced the Salmonella population. Thus, these strains exhibit considerable promise for producing biotechnological products aimed at controlling Salmonella in animal production. This approach ensures the health and hygiene of farming facilities, mitigates the spread of zoonotic bacteria, and contributes positively to public health.

3.
Med. U.P.B ; 43(1): 107-112, ene.-jun. 2024. ilus
Artículo en Español | LILACS, COLNAL | ID: biblio-1531524

RESUMEN

La tuberculosis aún es un problema de salud pública mundial. La infección causada por Mycobacterium tuberculosis se manifiesta de forma principal a nivel pulmonar. Sin embargo, alrededor del 20 % de los casos se presentan en otras localizaciones anatómicas y solo el 2 % tiene afectación del tracto respiratorio superior. Se presenta el caso de una mujer de 75 años, reconsultante al servicio de otorrinolaringología por epistaxis, lesiones postillosas en cavidad nasal y hallazgo de masa nasal. Posterior a la resección quirúrgica de la lesión, se logró la comprobación microbiológica de infección por M. tuberculosis. Se realizan estudios para descartar compromiso pulmonar y de otras localizaciones. Posterior al inicio de tratamiento antituberculoso se logró resolución completa de la lesión y no recurrencia de los síntomas. Las formas extrapulmonares de la infección por M. tuberculosis y, en especial las que afectan la región de la cabeza y el cuello, requieren un alto índice de sospecha para su diagnóstico. Los métodos de diagnóstico como la prueba de PCR y los cultivos de tejidos permiten un óptimo inicio del manejo médico de acuerdo con la epidemiología local y las condiciones del paciente.


Tuberculosis is still a global public health burden. Infection caused by the bacillus Mycobacterium tuberculosis (M. Tuberculosis) manifests mainly in the lungs. However, around 20 % of cases occur in other anatomical locations and only 2 % have upper respiratory tract involvement. We present the case of a 75-year-old female patient, who returned to the otorhinolaryngology service due to epistaxis and postillomous lesions in the nasal cavity with a finding of a nasal mass. After surgical resection of the lesion, microbiological confirmation of M. tuberculosis infection is achieved. Studies are performed to rule-out lung involvement, as well as other locations. After the initiation of tuberculosis treatment, complete resolution of the lesion and no recurrence of symptoms is documented. Extrapulmonary forms of M. tuberculosis infection, and especially those involving the head and neck region, require a high index of suspicion for their diagnosis. Diagnostic methods such as PCR testing and tissue cultures allow optimal initiation of medical management according to local epidemiology and patient conditions.


A tuberculose ainda é um problema de saúde pública global. A infecção causada pelo Mycobacterium tuberculoses manifesta-se principalmente nos pulmões. Entretanto, cerca de 20% dos casos ocorrem em outras localizações anatômicas e apenas 2% apresentam comprometimento do trato respiratório superior. É apresentado o caso de uma mulher de 75 anos que retornou ao serviço de otorrinolaringologia por quadro de epistaxe, lesões com crostas em cavidade nasal e descoberta de massa nasal. Após ressecção cirúrgica da lesão, foi realizada verificação microbiológica de infecção por M. tuberculoses. Estudos são realizados para descartar envolvimento pulmonar e otras localizações. Após início do tratamento antituberculoso, houve resolução completa dalesão e não houve recidiva dos sintomas. As formas extrapulmonares da infecção por M. tuberculoses, especialmente aquelas que acometem a região de cabeça e pescoço, requerem alto índice de suspeita para diagnóstico. Métodos de diagnóstico, como testes de PCR e culturas de tecidos, permitem o início ideal do tratamento médico de acordó com a epidemiologia local e as condições do paciente.


Asunto(s)
Humanos
4.
FEMS Microbiol Lett, v. 371, fnae033, mai, 2024
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5372

RESUMEN

The COVID-19 pandemic has posed challenges for education, particularly in undergraduate teaching. In this study, we report on the experience of how a private university successfully addressed this challenge through an active methodology applied to a microbiology discipline offered remotely to students from various health-related courses (veterinary, physiotherapy, nursing, biomedicine, and nutrition). Remote teaching was combined with the “Adopt a Bacterium” methodology, implemented for the first time on Google Sites. The distance learning activity notably improved student participation in microbiology discussions, both through word cloud analysis and the richness of discourse measured by the Shannon index. Furthermore, feedback from students about the e-learning approach was highly positive, indicating its effectiveness in motivating and involving students in the learning process. The results also demonstrate that despite being offered simultaneously to students, the methodology allowed for the acquisition of specialized knowledge within each course and sparked student interest in various aspects of microbiology. In conclusion, the remote “Adopt a Bacterium” methodology facilitated knowledge sharing among undergraduate students from different health-related courses and represented a valuable resource in distance microbiology education.

5.
ACS Meas Sci Au ; 3(5): 355-360, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37868361

RESUMEN

Due to the increasing demand for clinical testing of infectious diseases at the point-of-care, the global market claims alternatives for rapid diagnosis tools such as disposable biosensors, avoiding the need for specialized laboratories and skilled personnel. Bacterial vaginosis (BV) is an infectious disease that commonly affects reproductive-age women and predisposes the infection of sexually transmitted diseases. Especially in asymptomatic cases, BV can lead to pelvic inflammatory conditions, postpartum endometritis, and preterm labor. Conventionally, BV diagnosis involves the microscopic analysis of vaginal swab samples; it thus requires highly trained personnel. In response, we report a novel microfluidic paper-based analytical device for BV diagnosis. Sialidase, a biomarker overexpressed in BV, was detected by exploiting an immunosensing mechanism previously discovered by our team. This technology employs a graphene oxide-coated surface as a quencher of fluorescence; the fluorescence of the immunoprobes that do not experiment immunoreactions (antibody-antigen) are deactivated by graphene oxide via non-radiative energy transfer, whereas those immunoprobes undergoing immunoreactions preserve their photoluminescence due to the distance and the low affinity between the immunocomplex and the graphene oxide-coated surface. Our paper-based test was typically carried out within 20 min, and the sample volume was 6 µL. Besides, it was tested with 14 vaginal swabs specimens to discriminate clinical samples of women with normal microbiota from those with BV. Our disposable device represents a new tool to prevent the consequences of BV.

6.
Sci Rep ; 13(1): 16821, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798298

RESUMEN

Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes.


Asunto(s)
COVID-19 , Pyrococcus furiosus , Humanos , Animales , Ratones , Epítopos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Pyrococcus furiosus/metabolismo , Anticuerpos Antivirales , Proteínas del Envoltorio Viral , SARS-CoV-2 , Péptidos/química , Anticuerpos Neutralizantes
7.
Polymers (Basel) ; 15(12)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37376275

RESUMEN

Several diseases and injuries cause irreversible damage to bone tissues, which may require partial or total regeneration or replacement. Tissue engineering suggests developing substitutes that may contribute to the repair or regeneration process by using three-dimensional lattices (scaffolds) to create functional bone tissues. Herein, scaffolds comprising polylactic acid and wollastonite particles enriched with propolis extracts from the Arauca region of Colombia were developed as gyroid triply periodic minimal surfaces using fused deposition modeling. The propolis extracts exhibited antibacterial activity against Staphylococcus aureus (ATCC 25175) and Staphylococcus epidermidis (ATCC 12228), which cause osteomyelitis. The scaffolds were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, contact angle, swelling, and degradation. Their mechanical properties were assessed using static and dynamic tests. Cell viability/proliferation assay was conducted using hDP-MSC cultures, while their bactericidal properties against monospecies cultures (S. aureus and S. epidermidis) and cocultures were evaluated. The wollastonite particles did not affect the physical, mechanical, or thermal properties of the scaffolds. The contact angle results showed that there were no substantial differences in the hydrophobicity between scaffolds with and without particles. Scaffolds containing wollastonite particles suffered less degradation than those produced using PLA alone. A representative result of the cyclic tests at Fmax = 450 N showed that the maximum strain reached after 8000 cycles is well below the yield strain (i.e., <7.5%), thereby indicating that even under these stringent conditions, these scaffolds will be able to work properly. The scaffolds impregnated with propolis showed a lower % of cell viability using hDP-MSCs on the 3rd day, but these values increased on the 7th day. These scaffolds exhibited antibacterial activity against the monospecies cultures of S. aureus and S. epidermidis and their cocultures. The samples without propolis loads did not show inhibition halos, whereas those loaded with EEP exhibited halos of 17.42 ± 0.2 mm against S. aureus and 12.9 ± 0.5 mm against S. epidermidis. These results made the scaffolds possible bone substitutes that exert control over species with a proliferative capacity for the biofilm-formation processes required for typical severe infectious processes.

8.
Front Public Health ; 11: 1095162, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304100

RESUMEN

The historical and social vulnerability of quilombola communities in Brazil can make them especially fragile in the face of COVID-19, considering that several individuals have precarious health systems and inadequate access to water. This work aimed to characterize the frequency of SARS-COV-2 infections and the presence of IgM and IgG SARS-CoV-2 antibodies in quilombola populations and their relationship with the presence of risk factors or preexisting chronic diseases in the quilombola communities. We analyzed the sociodemographic and clinical characteristics, serological status, comorbidities, and symptoms of 1,994 individuals (478 males and 1,536 females) from 18 Brazilian municipalities in the State of Sergipe of quilombola communities, which were evaluated at different epidemiological weeks, starting at the 32nd (August 6th) and ending at the 40th (October 3rd) epidemiological week. More than 70% of studied families live in rural areas and they have an extreme poverty social status. Although we found a higher number of SARS-COV-2 infections in quilombola communities than in the local population, their SARS-CoV-2 reactivity and IgM and IgG positivity varied across the communities investigated. Arterial hypertension was the most risk factor, being found in 27.8% of the individuals (9.5% in stage 1, 10.8% in stage 2, and 7.5% in stage 3). The most common COVID-19 symptoms and comorbidities were headache, runny nose, flu, and dyslipidemia. However, most individuals were asymptomatic (79.9%). Our data indicate that mass testing must be incorporated into public policy to improve the health care system available to quilombola populations during a future pandemic or epidemic.


Asunto(s)
COVID-19 , Femenino , Masculino , Humanos , COVID-19/epidemiología , Brasil/epidemiología , SARS-CoV-2 , Pandemias , Inmunoglobulina G , Inmunoglobulina M
9.
FEMS Microbiol Lett ; 3702023 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-37385827

RESUMEN

Traditional lab classes in microbiology are common in several educational institutions, which can provide a learning experience disconnected from the myriad of experiments performed in research laboratories. Attempting to promote an authentic learning opportunity of the functioning of a bacteriology research laboratory, we developed the "Real-Lab-Day," a multimodal learning experience to develop competencies, abilities, critical analysis, and teamwork skills for undergraduate students. Students were divided into groups and assigned to research laboratories to be mentored by graduate students, to design and carry out scientific assays. Undergraduate students were introduced to methods such as cellular and molecular assays, flow cytometry, and fluorescence microscopy, as tools to address scientific questions about bacterial pathogenicity, bacterial resistance, and other topics. To consolidate their learning, students created and presented a poster in a rotational panel of peer learning. The perceived learning and interest in microbiology research were improved by the Real-Lab-Day experience, and >95% of the students approved the Real-Lab-Day as a teaching tool in microbiology. Students exposed to a research laboratory had a positive experience with the teaching method, and over 90% saw it as beneficial to improve their understanding of the scientific concepts discussed during lectures. Likewise, their interest in pursuing a career in microbiology was stimulated by the Real-Lab-Day experience. In conclusion, this educational initiative depicts an alternative methodology to connect students to the research and offers an opportunity to be in close contact with experts and graduate students, who gain teaching experience.


Asunto(s)
Curriculum , Educación de Pregrado en Medicina , Humanos , Aprendizaje , Estudiantes , Instituciones Académicas , Educación de Pregrado en Medicina/métodos , Microbiología/educación
10.
Materials (Basel) ; 16(6)2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36984148

RESUMEN

Ba0.92Ca0.08Ti0.95Zr0.05O3 (BCZT8-5) ceramic materials have been scarcely studied as lead-free piezo/ferroelectrics despite their enhanced Curie temperature (>100 °C) with respect to most studied BCZT compositions. In this work, homogeneous dense BCZT8-5 ceramics with grain size in the range of 20 µm, and optimum ferroelectric, dielectric, and electromechanical performance, were prepared by the mixed oxides route using moderate synthesis (1250 °C-2 h) and sintering (1400 °C-2 h) conditions. Thickness-poled thin disks and monomodal shear plate resonators were used for the determination of piezoelectric coefficients, coupling factors, elastic, and dielectric permittivity coefficients, including all losses, by iterative analysis of impedance curves at resonance. Furthermore, the thermal evolution of the piezoelectric characteristics at resonance was determined to assess the enhanced working range of the ceramics (≈100 °C). Ferroelectric hysteresis loops and strains vs. electric-field butterfly loops were also measured and showed soft behavior with Ec = 2 kV/cm, Pr = 12 µC/cm2 after a maximum applied field of 3 kV was used. The ceramics showed a high endurance of P-E cycles to electrical fatigue up to 107 cycles. Moreover, dielectric properties as a function of temperature were also accomplished and showed nearly normal ferroelectric behavior, characteristic of samples with low crystallographic disorder. Overall, these ceramics showed high sensitivity and higher stability than other currently studied BCZT compositions.

11.
Sci Transl Med ; 15(686): eabn3464, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36867683

RESUMEN

As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Vacunas de ADN , Animales , Femenino , Ratones , Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Inmunización , Ratones Endogámicos C57BL , Neoplasias/terapia , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/genética , Proteínas Recombinantes , ARN Mensajero/genética
12.
Heliyon ; 9(2): e13176, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36798758

RESUMEN

The increase in critical bone diseases and defects in the world's population increases the need for bone substitutes to restore form and function. Organic and inorganic scaffolds with antibacterial properties could provide advantages for bone regeneration. In this study, we obtained scaffolds of polycaprolactone (PCL) charged with calcium phosphates nanoparticles and impregnated with extracts of Colombian plants as an alternative for potential bone regeneration. Calcium phosphate nanoparticles were obtained via auto-combustion synthesis. The nanoparticles were incorporated into the PCL with a chemical dissolution-disperse process. The composite obtained was used to produce a filament to print Triply Periodic Minimal Surface (TPMS) based scaffolds. Such geometry facilitates cellular growth thanks to its interconnected porosity. The scaffolds were impregnated with extracts of Justicia cf colorifera (Acanthaceae), and Billia rosea (Sapindaceae) due to their ancestral medical applications. A physical and biological characterization was conducted. The process to print scaffolds with an enhanced geometry to facilitate the flux of biological fluids was successful. The scaffolds loaded with B. rosea showed strong antibacterial behavior, suggesting the presence of reported terpenoids with antibacterial properties. The approach used in this study evidenced promising prospects for bone defect repair.

13.
Sci Rep, v. 13, 16821, out. 2023
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5124

RESUMEN

Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes.

14.
FEMS Microbiol Lett, v. 370. jun. 2023
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-4993

RESUMEN

Traditional lab classes in microbiology are common in several educational institutions, which can provide a learning experience disconnected from the myriad of experiments performed in research laboratories. Attempting to promote an authentic learning opportunity of the functioning of a bacteriology research laboratory, we developed the “Real-Lab-Day,” a multimodal learning experience to develop competencies, abilities, critical analysis, and teamwork skills for undergraduate students. Students were divided into groups and assigned to research laboratories to be mentored by graduate students, to design and carry out scientific assays. Undergraduate students were introduced to methods such as cellular and molecular assays, flow cytometry, and fluorescence microscopy, as tools to address scientific questions about bacterial pathogenicity, bacterial resistance, and other topics. To consolidate their learning, students created and presented a poster in a rotational panel of peer learning. The perceived learning and interest in microbiology research were improved by the Real-Lab-Day experience, and >95% of the students approved the Real-Lab-Day as a teaching tool in microbiology. Students exposed to a research laboratory had a positive experience with the teaching method, and over 90% saw it as beneficial to improve their understanding of the scientific concepts discussed during lectures. Likewise, their interest in pursuing a career in microbiology was stimulated by the Real-Lab-Day experience. In conclusion, this educational initiative depicts an alternative methodology to connect students to the research and offers an opportunity to be in close contact with experts and graduate students, who gain teaching experience.

16.
Front Immunol ; 13: 1005937, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36405719

RESUMEN

High-risk Human papillomavirus (HPV) infections represent an important public health issue. Nearly all cervical malignancies are associated with HPV, and a range of other female and male cancers, such as anogenital and oropharyngeal. Aiming to treat HPV-related tumors, our group developed vaccines based on the genetic fusion of the HSV-1 glycoprotein D (gD) with the HPV-16 E7 oncoprotein (gDE7 vaccines). Despite the promising antitumor results reached by gDE7 vaccines in mice, combined therapies may increase the therapeutic effects by improving antitumor responses and halting immune suppressive mechanisms elicited by tumor cells. Considering cancer immunosuppressive mechanisms, indoleamine-2,3-dioxygenase (IDO) enzyme and interleukin-6 (IL-6) stand out in HPV-related tumors. Since IL-6 sustained the constitutive IDO expression, here we evaluated the therapeutic outcomes achieved by the combination of active immunotherapy based on a gDE7 protein-based vaccine with adjuvant treatments involving blocking IDO, either by use of IDO inhibitors or IL-6 knockout mice. C57BL/6 wild-type (WT) and transgenic IL-6-/- mice were engrafted with HPV16-E6/E7-expressing TC-1 cells and treated with 1-methyl-tryptophan isoforms (D-1MT and DL-1MT), capable to inhibit IDO. In vitro, the 1MT isoforms reduced IL-6 gene expression and IL-6 secretion in TC-1 cells. In vivo, the multi-targeted treatment improved the antitumor efficacy of the gDE7-based protein vaccine. Although the gDE7 immunization achieves partial tumor mass control in combination with D-1MT or DL-1MT in WT mice or when administered in IL-6-/- mice, the combination of gDE7 and 1MT in IL-6-/- mice further enhanced the antitumor effects, reaching total tumor rejection. The outcome of the combined therapy was associated with an increased frequency of activated dendritic cells and decreased frequencies of intratumoral polymorphonuclear myeloid-derived suppressor cells and T regulatory cells. In conclusion, the present study demonstrated that IL-6 and IDO negatively contribute to the activation of immune cells, particularly dendritic cells, reducing gDE7 vaccine-induced protective immune responses and, therefore, opening perspectives for the use of combined strategies based on inhibition of IL-6 and IDO as immunometabolic adjuvants for immunotherapies against HPV-related tumors.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Masculino , Humanos , Femenino , Ratones , Animales , Interleucina-6 , Ratones Endogámicos C57BL , Papillomaviridae , Inmunoterapia , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo
17.
Life Sci ; 309: 121017, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36183779

RESUMEN

AIM: To analyze the consumption of oxygen and to quantify the mitochondrial respiratory chain proteins (OXPHOS) in the gastrocnemius muscle of rats exposed to cigarette smoke and/or RT practitioners. MAIN METHODS: Wistar rats were divided into groups: Control (C), Smoker (S), Exercise (E) and Exercise Smoker (ES). Groups F and ES were exposed to the smoke of 4 cigarettes for 30 min, 2× a day, 5× a week, for 16 weeks. Groups E and ES performed four climbs with progressive load, 1× per day, 5× per week, for 16 weeks. The gastrocnemius muscle was collected for analysis of OXPHOS content and oxygen consumption. Groups S (vs. C) and ES (vs. C and E) showed lower body weight gain when observing the evolution curve. KEY FINDINGS: The S rats showed a reduction in the NDUFB8 proteins of complex 1, SDHB of complex 2, MTC01 of complex 4 and ATP5A of complex 5 (ATP Synthase) compared to Group C. Additionally, S rats also showed increased consumption of O2 in Basal, Leak, Complex I and I/II combined measures compared to the other groups, suggesting that the activity of the mitochondria of these animals increased in terms of coupling and uncoupling parameters. SIGNIFICANCE: Our data suggest that exposure to cigarette smoke for 16 weeks is capable of causing impairment of mitochondrial function with reduced expression of respiratory chain proteins in skeletal muscle. However, the RT was effective in preventing impairment of mitochondrial function in the skeletal muscle of rats exposed to secondary cigarette smoke.


Asunto(s)
Fumar Cigarrillos , Entrenamiento de Fuerza , Humanos , Ratas , Animales , Ratas Wistar , Músculo Esquelético/metabolismo , Mitocondrias , Nicotiana/efectos adversos , Oxígeno/metabolismo , Adenosina Trifosfato/metabolismo
19.
Rev. cuba. enferm ; 38(1)mar. 2022.
Artículo en Español | LILACS, BDENF - Enfermería, CUMED | ID: biblio-1408319

RESUMEN

Introducción: La fatiga constituye un importante problema de salud que precisa de una adecuada valoración, diagnóstico y planificación de cuidados enfermeros centrados en quienes la sufren. Objetivo: Validar el contenido del diagnóstico enfermero NANDA-I Fatiga (00093) en la versión incluida en una base de datos clínica. Métodos: Estudio descriptivo y exploratorio de validación de contenido diagnóstico mediante expertos siguiendo la propuesta de Fehring. El ámbito de estudio fue España. La recogida de datos se realizó entre los meses de junio 2019-marzo 2020. Los expertos participantes disponían de experiencia y formación en el uso de lenguajes estandarizados enfermeros. Resultados: De las 13 Características Definitorias con las que cuenta el diagnóstico incluido en la base de datos, siete fueron validadas como mayores, cinco como menores y una no fue validada. Los 16 Factores Relacionados del diagnóstico fueron validados. El Índice de Validez de Contenido del diagnóstico fue de 0,81. Conclusiones: El diagnóstico obtuvo un Índice de Validez de Contenido elevado. Los componentes del diagnóstico NANDA-I Fatiga (00093) en la versión de la base de datos clínica guardan correspondencia con los presentes en el diagnóstico NANDA-I Fatiga (00093) en la Clasificación NANDA-I 2018-2020. Se considera que la investigación actual contribuye a incrementar la precisión diagnóstica al identificar Características Definitorias claves de la presencia del diagnóstico. Al tiempo valida Factores Relacionados influyentes en el diagnóstico no incorporados en los componentes del diagnóstico NANDA-I Fatiga (00093) en la edición de la Clasificación NANDA-I 2018-2020(AU)


Introduction: Fatigue is an important health concern that requiring appropriate assessment, diagnosis and nursing care planning focused on those who suffer from it. Objective: To validate the content of NANDA-I nursing diagnosis of fatigue (00093) in the version included in a clinical database. Methods: Descriptive and exploratory study of diagnostic content validation by experts following Fehring's proposal. The setting of the study was Spain. Data collection was carried out between June 2019 and March 2020. The participating experts had experience and training in the use of standardized nursing languages. Results: Of the thirteen characteristics that define the diagnosis included in the database, seven were validated as major, five as minor and one was not validated. All sixteen related factors of the diagnosis were validated. The content validity index of the diagnosis was 0.81. Conclusions: The diagnosis obtained a high content validity index. The components of the NANDA-I diagnosis of fatigue (00093) in the clinical database version correspond with those present in the NANDA-I diagnosis of fatigue (00093) in the NANDA-I Classification 2018-2020. The current research is considered to contribute with an increase in diagnostic accuracy by identifying key defining characteristics for the diagnosis. At the same time, it validates related factors that have an influence on the diagnosis but are not incorporated among the components of the NANDA-I diagnosis of fatigue (00093) in the 2018-2020 edition of the NANDA-I Classification(AU)


Asunto(s)
Humanos , Diagnóstico de Enfermería/métodos , Fatiga/etiología , Terminología Normalizada de Enfermería , Atención de Enfermería/métodos , Correspondencia como Asunto , Epidemiología Descriptiva , Recolección de Datos , Estudios de Validación como Asunto
20.
Int J Biol Sci ; 18(1): 15-29, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34975315

RESUMEN

The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8+ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8+ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors.


Asunto(s)
Vacunas contra el Cáncer/farmacología , Cisplatino/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/virología , Infecciones por Papillomavirus/complicaciones , Animales , Ratones , Ratones Endogámicos C57BL , Recurrencia Local de Neoplasia/prevención & control , Neoplasias/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
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