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In Mexico, more than 30 species of triatomines, vectors of Trypanosoma cruzi, the etiological agent of Chagas disease, have been collected. Among them, Triatoma pallidipennis stands out for its wide geographical distribution, high infection rates and domiciliation. Local populations of triatomines have shown notable biological and behavioral differences, influencing their vectorial capacity. Six behaviors of epidemiological importance, namely, egg-to-adult development time, median number of blood meals to molt to the next instar, instar mortality rates, aggressiveness (delay in initiating a meal), feeding time and defecation delay, were evaluated in this study for six populations of T. pallidipennis. Those populations from central, western and southern Mexico were arranged by pairs with a combination of high (HP) and medium (MP) of Trypanosoma cruzi human infection and most (MFC) and low (CLF) collection frequencies: HP/MFC, HP/CLF, and MP/MFC. The development time was longer in HP/CLF populations (> 220 days). The median number of blood meals to molt was similar (7-9) among five of the six populations. Mortality rates were greater (> 40 %) in HP/CLF and one MP/MFC populations. All studied populations were aggressive but exhibited slight differences among them. The feeding times were similar (≥ 10 min) for all studied populations within instars, increasing as instars progressed. An irregular pattern was observed in defecation behaviors, with marked differences even between the two populations from the same pair. High percentages of young (57.3-87.9 %), and old (62.4-89.8 %) nymphs, of female (61.1-97.3 %) and male (65.7-93.1 %) of all the studied populations defecated quickly (while eating, immediately after finishing feeding or < 1 min postfeeding). Our results indicate that the HP/MFC populations are potentially highly effective vectors for transmitting T. cruzi infections, while HP/CLF populations are potentially less effective vectors T. cruzi infections.

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BACKGROUND: To describe an oncolytic adenovirus (OAd) encoding SP-SA-E7-4-1BBL that is capable of inducing tumor regression in therapeutic assays. Herein, we tested whether the antitumor effect is given by the induction of a tumor-specific immune response, as well as the minimum dose needed to elicit antitumor protection and monitor the OAd biodistribution over time. METHODS AND RESULTS: C57BL/6 mice (n = 5) per group were immunized twice with OAds encoding SP-SA-E7-4-1BBL, SA-E7-4-1BBL, or SP-SA-4-1BBL and challenged with TC-1 cancer cells. The DNA construct SP-SA-E7-4-1BBL was employed as a control via biolistic or PBS injection. Groups without tumor development at 47 days were rechallenged with TC-1 cells, and follow-up lasted until day 90. The minimum dose of OAd to induce the antitumor effect was established by immunization using serial dilution doses. The cytometry bead assay and the ELISpot assay were used to evaluate cytokine release in response to ex vivo antigenic stimulation. The distribution profile of the OAd vaccine was evaluated in the different organs by histological, immunohistochemical and qPCR analyses. The OAd SP-SA-E7-4-1BBL-immunized mice did not develop tumors even in a rechallenge. A protective antitumor effect was observed from a dose that is one hundredth of most reports of adenoviral vaccines. Immunization with OAd increases Interferon-gamma-producing cells in response to antigen stimulation. OAd was detected in tumors over time, with significant morphological changes, contrary to nontumor tissues. CONCLUSIONS: The OAd SP-SA-E7-4-1BBL vaccine confers a prophylactic, safe, long-lasting, and antigen-dependent antitumor effect mediated by a Th1 antitumor immune response.

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Entomopathogenic nematodes have been used in biological control for some time and are an alternative for the control of insect pests, but during their implementation, situations have arisen that can be improved. These vary with each species and include their production and storage. Oscheius myriophila, an entomopathogenic nematode (EPN), was monitored for its performance when produced in vivo, as well as its development using Galleria mellonella larvae, using the MC5-2014 strain isolated from soil samples in the municipality of Tepalcingo, Morelos, México. For a study with native strains of EPNs, a wide range of tests must be conducted because the required conditions can be very specific. In vivo production was quantified at initial infective juvenile (IJ) inocula of 50, 100 and 500, and we obtained the same production for the three inocula. The life cycle of the EPNs lasted 12 days, and two generations were observed in which adults were found at days 5 and 9. Both evaluations were performed at a temperature of 27 °C in G. mellonella larvae. In addition, the temperatures of 8, 12, 20 and 24 °C were evaluated for their storage, and we observed that the EPNs can be kept for at least 6 months, maintaining a survival rate of 58.67% and a good infective capacity at a temperature of 12 °C, remaining above 60%.

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Introducción: El programa de estudio es una formulación hipotética de los aprendizajes que se pretenden lograr en el educando. Constituye una herramienta fundamental de trabajo docente. Objetivo: Exponer un análisis crítico del programa de estudio de la asignatura Genética Médica en la carrera de medicina, a partir de lo normado en el reglamento vigente para el trabajo docente-metodológico. Métodos: Se realizó una revisión bibliográfica para desarrollar un análisis crítico del programa de la asignatura genética médica, en la que se consideraron artículos publicados entre 2012 y 2022. La búsqueda fue realizada en Google académico, Dialnet, SciELO y Redalyc en septiembre de 2022. Las palabras clave utilizadas fueron: programas, genética, asignatura, disciplina y proceso docente-educativo. Dentro de este marco se incluyeron todos los artículos cubanos publicados; no hubo restricción en cuanto al idioma. Se consultaron 50 artículos, de estos 11 fueron seleccionados. Se excluyeron aquellos no relacionados con la educación médica superior. Resultados: Se orientó metodológicamente la inclusión de aspectos encaminados a la promoción de salud; fomentar las habilidades comunicativas; reformular los objetivos, incluyendo en su estructura los elementos esenciales; realizar un cambio en el orden de impartir el contenido, con modificaciones, además, en el nivel de profundidad y con aporte de un enfoque preventive; y declarar adecuadamente los valores, la rectificación de la cantidad de horas del fondo de tiempo y la actualización de la bibliografía. Conclusiones: Las insuficiencias encontradas en el análisis efectuado identificaron las áreas vulnerables hacia donde deben dirigirse las principales acciones encaminadas a aumentar la calidad del proceso docente educativo y reflejaron la necesidad de su reevaluación(AU)

Introduction: The syllabus is a hypothetical formulation of the learning aspects intended to be achieved in the student. It is a fundamental tool for teaching. Objective: To present a critical analysis of the syllabus for subject Medical Genetics in the medical major, based on the current regulations for the teaching-methodological work. Methods: A literature review was carried out to develop a critical analysis of the syllabus of the subject Medical Genetics, considering articles published between 2012 and 2022. The search was performed in Google Scholar, Dialnet, SciELO and Redalyc in September 2022. The keywords used were programas [syllabuses], genética [genetics], asignatura [subject], disciplina [discipline] and proceso docente-educativo [teaching-educational process]. This framework included all published Cuban articles; there were not any language-related restrictions. Fifty articles were consulted, 11 of which were selected. Those not related to higher medical education were excluded. Results: The methodological orientation was to include aspects aimed at health promotion, to encourage communicative skills, to reformulate the objectives (including the essential elements in their structure), to make a change in the order of teaching (with modifications also in the level of depth and contributing with a preventive approach), as well as to state the values adequately, to rectify the number of hours within the available time fund, to update the bibliography. Conclusions: The insufficiencies found through the performed analysis permitted to identify the vulnerable areas towards the main actions should be directed if aimed at increasing the quality of the educational teaching process, apart from reflecting their need to be reassessed(AU)

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Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

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BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

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Resumen ANTECEDENTES: La trombosis del seno venoso representa el 1% de los eventos vasculares cerebrales; su incidencia es de 5 casos por cada millón de habitantes y su mortalidad es del 10%. Los senos sagital superior y venoso transversal son los más afectados. El embarazo es un factor de riesgo especial pues la trombosis se registra en el 0.01% de las gestaciones. CASO CLÍNICO: Paciente de 40 años, primigesta, con embarazo gemelar bicorial biamniótico de 33.6 semanas. Se ingresó al servicio de Urgencias debido al diagnóstico de preeclampsia con criterios de severidad, con presión arterial de 160-100 mmHg y transaminasemia. Se le indicó tratamiento antihipertensivo y sulfato de magnesio intravenoso. Se decidió la finalización del embarazo por cesárea. Al cuarto día poscesárea tuvo disminución de la fuerza en ambos brazos, pérdida del tono muscular en los miembros pélvicos, cefalea holocraneana y alteración del estado de alerta (Glasgow de 14). Mediante resonancia magnética se evidenció la oclusión del seno longitudinal superior e isquemia en la región parieto occipital izquierda. Se le administraron anticoagulantes y analgésicos con los que evolucionó adecuadamente; se dio de alta sin complicaciones. CONCLUSIONES: La trombosis del seno venoso implica un reto cuando no se tiene una alta sospecha diagnóstica en pacientes con signos y síntomas neurológicos y, más aún, cuando se agregan factores de riesgo protrombóticos, como el embarazo y el puerperio. El diagnóstico oportuno brinda la oportunidad de iniciar el tratamiento adecuado y disminuir los síntomas y comorbilidades.

Abstract BACKGROUND: Venous sinus thrombosis accounts for 1% of cerebral vascular events; its incidence is 5 cases per million population and its mortality is 10%. The superior sagittal and transverse venous sinuses are the most affected. Pregnancy is a special risk factor since thrombosis is registered in 0.01% of pregnancies. CLINICAL CASE: A 40-year-old primigravida patient with a 33.6 week biamniotic twin pregnancy. She was admitted to the Emergency Department due to the diagnosis of preeclampsia with severity criteria, with blood pressure of 160-100 mmHg and transaminasemia. She was prescribed antihypertensive treatment and intravenous magnesium sulfate. It was decided to terminate the pregnancy by cesarean section. On the fourth post-cesarean day she had decreased strength in both arms, loss of muscle tone in the pelvic limbs, holocranial headache and altered alertness (Glasgow of 14). Magnetic resonance imaging showed occlusion of the superior longitudinal sinus and ischemia in the left parietooccipital region. He was administered anticoagulants and analgesics with which he evolved adequately; he was discharged without complications. CONCLUSIONS: Venous sinus thrombosis implies a challenge when there is no high diagnostic suspicion in patients with neurological signs and symptoms and, even more so, when prothrombotic risk factors are added, such as pregnancy and puerperium. Timely diagnosis provides the opportunity to initiate appropriate treatment and reduce symptoms and comorbidities.

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Hair graying, a prototypical sign of human aging, is a progressive loss of pigmentation from growing hair shafts caused by disease and as a side effect of medications. Cerebrolysin is a neuropeptide preparation that mimics the effect of endogenous neurotrophic factors. Cerebrolysin has been widely used in neurologic conditions, such as cerebral stroke, Alzheimer's disease, and dementia, among others. Cerebrolysin treatment has achieved to regain or maintain the cognitive ability of affected patients; however, up to date, there are no reports about the reactivation of hair pigmentation. We describe a previously not described effect occurring on patients receiving Cerebrolysin treatment for neurologic diseases and whether this effect is associated in reactivation of melanocytes and melanin expression. Here, we report five patients (mean age, 70.6 years), who also had age-related hair graying and scalp hair repigmentation during Cerebrolysin treatment. Macroscopic analysis revealed hair repigmentation consisted in diffuse darkening of the scalp hair. Impregnation and immunostaining analysis were performed on scalp biopsies taken before and after Cerebrolysin treatment; the results showed greater melanin and melanocyte marker MART-1/Melan-A staining following Cerebrolysin treatment. We present, to our knowledge, the first report on hair repigmentation is a previously not described effect occurring following Cerebrolysin treatment.

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A large area of the terrestrial land surface is used for livestock grazing. Trees on grazing lands provide and can enhance multiple ecosystem services such as provisioning, cultural and regulating, that include carbon sequestration. In this study, we assessed the above- and belowground carbon stocks across six different land-uses in livestock-dominated landscapes of Mexico. We measured tree biomass and soil organic carbon (SOC) stocks in fodder banks, live fences, pasturelands with dispersed trees, secondary forests, and primary forests from three different geographical regions and compared them with conventional open pasturelands respectively. We also calculated tree diversity indices for each land-use and their similarity with native primary forests. The aboveground woody biomass stocks differed significantly between land-uses and followed the gradient from less diverse conventional open pasturelands to silvopastoral systems and ecologically complex primary forests. The SOC stocks showed a differential response to the land-use gradient dependent on the study region. Multivariate analyses showed that woody biomass, fine root biomass, and SOC concentrations were positively related, while land-use history and soil bulk density showed an inverse relationship to these variables. Silvopastoral systems and forest remnants stored 27-163% more carbon compared to open pasturelands. Our results demonstrate the importance of promoting appropriate silvopastoral systems and conserving forest remnants within livestock-dominated landscapes as a land-based carbon mitigation strategy. Furthermore, our findings also have important implications to help better manage livestock-dominated landscapes and minimize pressures on natural protected areas and biodiversity in the hotspots of deforestation for grassland expansion.

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Recently, the interest in using nucleic acids for therapeutic applications has been increasing. DNA molecules can be manipulated to express a gene of interest for gene therapy applications or vaccine development. Plasmid DNA can be developed to treat different diseases, such as infections and cancer. In most cancers, the immune system is limited or suppressed, allowing cancer cells to grow. DNA vaccination has demonstrated its capacity to stimulate the immune system to fight against cancer cells. Furthermore, plasmids for cancer gene therapy can direct the expression of proteins with different functions, such as enzymes, toxins, and cytotoxic or proapoptotic proteins, to directly kill cancer cells. The progress and promising results reported in animal models in recent years have led to interesting clinical results. These DNA strategies are expected to be approved for cancer treatment in the near future. This review discusses the main strategies, challenges, and future perspectives of using plasmid DNA for cancer treatment.

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BACKGROUND: The true prevalence of Chagas disease in Mexico is unknown. However, it has been estimated that 1.1-4 million people are infected with Trypanosoma cruzi, which represents a potential risk for transmission of the disease via contaminated blood. AIM OF THE STUDY: To determine the Chagas disease seroprevalence in donors from eight blood banks in the north of Mexico City, and the northeast of the State of Mexico. STUDY DESIGN AND METHODS: Serum samples from blood donors (n = 515,038) were tested to detect the presence of anti-Trypanosoma cruzi antibodies in eight blood banks. The serologic screening test was performed in each of the blood banks. To confirm the seropositive blood donors, only two out of the eight blood banks used a test with a different principle with the aim of identifying anti-Trypanosoma cruzi antibodies. All tests were validated by the Mexican Institute for Epidemiological Diagnosis and Reference. RESULTS: One thousand two hundred and ten blood donors were seropositive for Trypanosoma cruzi, which represents a 0.23% seroprevalence (95% CI 0.22-0.25%). Of the seropositive blood donors, 97.03 % resided in the northeast area of the State of Mexico, Mexico City, and southern part of the State of Hidalgo. CONCLUSIONS: Active transmission of Chagas disease may be occurring in non-endemic regions in the northeast of the State of Mexico.

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Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

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BACKGROUND: Loss of volume is perhaps the most frustrating problem of fat grafting. The process of fat grafting depends on different variables such as harvesting, processing, and injection techniques. Results between studies that evaluate the effect of the cannula size on fat graft survival have been controversial. However, the role of the fenestration area of the cannula has not been described. METHODS: Four custom-made cannulas with a single fenestration were used for this study. Cannulas vary in diameter and area of the fenestration. Healthy patients seeking primary liposuction of the abdomen for aesthetic reasons were included. Lipoaspiration was performed in a clockwise pattern, and the order of the cannulas was rotated. Negative pressure was maintained at 0.8 atm at all times. Ten ml of fat, obtained from the suction tube, was poured into 20-ml conical centrifugal tubes for further processing. One gram of lipoaspirate was extracted from each sample, and acridine orange stain was added. Adipocytes were extracted, extended in a frotis, and observed by a histologist (masked fashion) under fluorescence microscopy. Viability was reported in percentages per sample. RESULTS: The overall viability was 64.75% ± 18.58. The viability of the obtained samples ranged from 66.51± 20.66 % to 62.83 ± 18.1. In further analysis, comparing the viability according to the shaft diameter and fenestration area, there was no significant difference among groups. CONCLUSIONS: Neither the diameter of the cannula nor the size of the fenestrations are determining factors to affect the viability of the adipocytes. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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Cartagena is subsiding at a higher rate compared to that of global climate-driven sea level rise. We investigate the relative sea level rise (RSLR) and the influence of vertical land movements in Cartagena through the integration of different datasets, including tide gauge records, GPS geodetic subsidence data, and Interferometric Synthetic Aperture Radar (InSAR) observations of vertical motions. Results reveal a long-term rate (> 60 years) of RSLR of 5.98 ± 0.01 mm/yr. The last two decades exhibited an even greater rate of RSLR of 7.02 ± 0.06 mm/yr. GPS subsidence rates range between - 5.71 ± 2.18 and - 2.85 ± 0.84 mm/yr. InSAR data for the 2014-2020 period show cumulative subsidence rates of up to 72.3 mm. We find that geologically induced vertical motions represent 41% of the observed changes in RSLR and that subsidence poses a major threat to Cartagena's preservation. The geodetic subsidence rates found would imply a further additional RSLR of 83 mm by 2050 and 225 mm by 2100. The Colombian government should plan for the future and serve as an example to similar cities across the Caribbean.

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The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.

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Population-based immunoglobulin G (IgG) seroprevalence studies in asymptomatic individuals in Latin America are scarce. The objective of the study was to estimate the prevalence and geographic distribution of IgG antibodies induced by natural SARS-CoV-2 infection in asymptomatic adults, 5-8 months after the first case was reported in a northeastern state of Mexico. This was a population-based cross-sectional study carried out in Nuevo Leon during August-November 2020. Individuals ≥18 years with no previous diagnosis or symptoms suggestive of COVID-19 were consecutively screened in one of the busiest subway stations. Also, a search for eligible individuals was done from house-to-house, after selecting densely populated geographic sectors of each of the municipalities of the metropolitan area (n = 4495). The IgG antibodies to SARS-CoV-2 nucleocapsid protein were analyzed. The IgG antibody positivity rate was 27.1% (95% confidence interval [CI]: 25.8, 28.4); there were no differences by sex or age (p > 0.05). Analysis by month showed a gradual increase from 11.9% (August) to 31.9% (November); Week 39 had the highest positivity rate (42.2%, 95% CI: 34.2, 50.7). Most people did not have evidence of previous SARS-CoV-2 infection. Preventive measures and promotion of the COVID-19 vaccine should be strengthened.

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White-rot fungi are efficient lignin degraders due to the secretion of lignin peroxidase, manganese peroxidase, laccase, and versatile peroxidase (VP) on decayed wood. The VP is a high-redox-potential enzyme and could be used to detoxify reactive oxygen species (ROS), which accumulate in plants during biotic and abiotic stresses. We cloned the VP gene and expressed it via the Agrobacterium transformation procedure in transgenic tobacco plants to assay their tolerance to different abiotic stress conditions. Thirty independent T2 transgenic VP lines overexpressing the fungal Bjerkandera adustaVP gene were selected on kanamycin. The VP22, VP24, and VP27 lines showed significant manganese peroxidase (MnP) activity. The highest was VP22, which showed 10.87-fold more manganese peroxidase activity than the wild-type plants and led to a 34% increase in plant height and 28% more biomass. The VP22, VP24, and VP27 lines showed enhanced tolerance to drought, 200 mM NaCl, and 400 mM sorbitol. Also, these transgenics displayed significant tolerance to methyl viologen, an active oxygen-generating compound. The present data indicate that overproducing the VP gene in plants increases significantly their biomass and the abiotic stress tolerance. The VP enzyme is an effective biotechnological tool to protect organisms against ROS. In transgenic tobacco plants, it improves drought, salt, and oxidative stress tolerance. Thus, the VP gene represents a great potential for obtaining stress-tolerant crops.

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Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, and regulatory immunity and, if fused to TAAs in DNA vaccines, can improve the antitumor response; however, there is low transfection and antitumor efficiency. Oncolytic virotherapy is promising for antitumor gene therapy as it can be selectively replicated in tumor cells, inducing cell lysis, and furthermore, tumor cell debris can be taken in by immune cells to potentiate antitumor responses. In this study, we expressed the immunomodulatory molecule SA-4-1BBL fused to E7 on an oncolytic adenovirus (OAd) system. In vitro infection of TC-1 tumor cells and NIH-3T3 non-tumor cells with SA/E7/4-1BBL OAd demonstrated that only tumor cells are selectively destroyed. Moreover, protein expression is targeted to the endoplasmic reticulum in both cell lines when a signal peptide (SP) is added. Finally, in an HPV-induced cancer murine model, the therapeutic oncolytic activity of OAd can be detected, and this can be improved when fused to E7 and SP.