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Mexico City emits several thousands of tons of particle matter from transportation and other economic sectors. We collected PM2.5 samples from January to March 2015. The chemical analyses showed that PM2.5 is made up of 39% organic carbon, 12% elemental carbon, 23% metals (Al, Si, S, P, and K), and 5% heavy metals (Pb, Cr, Mn, Zn, and Hg). Ca and Fe were also present in trace concentrations, probably due to the resuspension of soils. Nitrate, sulfate, and ammonium suggest that the southwest of Mexico City, specifically the sampling site, receives more oxidated pollutants from vehicle emissions than other emissions. The chemical analyses show no significant changes in the composition or concentration of particle matter compared to previous studies.

Heat waves (HW) are prolonged periods of excessively hot weather that can cause severe socioeconomic and environmental impacts. This study aims to evaluate the differences in stored heat and turbulent flux partitioning during a heat wave event in Mexico City, using observations from an eddy covariance tower during the period from 14 June to 21 June 2023. During this period, net radiation (Rn) and sensible heat flux (H) increased significantly, particularly from noon to evening, reflecting stable atmospheric conditions. The air temperature showed a noticeable increase in the afternoon and evening, whereas absolute humidity decreased. We found that during the heat wave, the Bowen ratio (β) increased by 80% during daylight hours and 65% over a full 24-hour period compared to the pre-heat wave period. This heat release at night prolonged warm conditions, intensifying heat stress. The partitioning of net radiation for latent heat (LE), sensible heat (H), and heat storage (ΔQs) showed significant changes; during the heat wave, 51% of Rn was allocated to H and 34% to ΔQs, compared to pre-heat wave values of 49% and 27%, respectively. This study introduces a new characterization of heat waves in terms of energy, emphasizing the significant shifts in energy flux partitioning and storage. The new characterization highlights the critical role of urban heat storage and its release in exacerbating heat stress during and after heat wave events. This approach provides a comprehensive understanding of the energy dynamics during heat waves, which is essential for developing effective mitigation strategies to combat the adverse effects of extreme heat in urban environments.

Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.

Forests embedded in an urban matrix are an important site to investigate the effects of multiple anthropogenic influences that can lead to the modification of biogeochemical cycles and, consequently, of the ecosystem services they provide. In this study, the main soil properties, exchangeable cations, and heavy metal concentrations were measured to assess soil quality and fertility, as well as soil carbon stock (SCS) and CO2 effluxes (Rs) at the Natural Protected Area Bosque de Tlalpan (BT). Four study zones were considered: strict protection zone (Z1), restricted use protection zone (Z2), extensive public use zone (Z3), and intensive public use zone (Z4) during three climatic seasons (rainy, dry-cold, and dry-warm seasons). The concentration of heavy metals in the BT soil showed that these elements are within the reference limits accepted by Mexican standards and are not considered toxic to the environment, except for mercury, which exceeded the standard with double the concentration. The results revealed significant variations in the SCS and soil organic matter (SOM) among the different sites. The highest mean values of SCS (3.01 ± 0.63 and 4.96 ± 0.19 kg m−2) and SOM (7.5 ± 1.01% and 8.7 ± 0.93%) were observed in areas of high protection and extensive public use. CO2 effluxes showed significant differences between sampling seasons, with fluxes being highest during the rainy season (3.14 ± 1.01 µmol∙m−2∙s−1). The results suggest that the level of conservation and effective management of the sites played an important role in the carbon storage capacity and in the physicochemical properties of the soil. This not only provided insights into the current state of an urban forest within a large urban area but also emphasized the significance of conserving such ecosystems.

From January to March 2015, an atmospheric aerosol measurement campaign, “Aerosoles en Ciudad Universitaria 2015” (ACU15), was carried out in Mexico City to determine the particles’ optical properties and chemical composition. Two photoacoustic spectrometers measured the scattering and absorption coefficient at two different wavelengths. The average absorption coefficient at 532 nm was 12.71 ± 9.48 Mm−1 and at 870 nm was 10.35 ± 7.36 Mm−1. The average scattering coefficient was 65.63 ± 47.12 Mm−1 (532 nm) and 21.12 ± 14.24 Mm−1 (870 nm). The chemical composition was determined via an aerosol chemical speciation monitor. The organic aerosol fraction represented 53% of the total PM1 and was made up of 63% low volatile (4.64 µg m−3), 22% hydrogenated (1.90 µg m−3), and 15% semi-volatile organics (1.54 µg m−3). The correlation coefficient of chemical species (NO3−, NH4+, SO42−, low-volatile, and semi-volatile organics) and optical properties was 0.92. The multilinear regression showed a good agreement among chemical species and optical properties (r > 0.7). The mass absorption coefficient calculated for the measuring site at 870 nm was MAE870 = 5.8 m2 g−1, instead of the default 4.74 m2 g−1. Furthermore, based on the median AAE, the 532 nm MAE532 resulting from the multiple linear regression (MLR) showed the following coefficients: 7.70 m2 g−1 (eBC), 0.22 m2 g−1 (HOA), and 0.16 m2 g−1 (LV–OOA). The coefficients of MLR were: 7.08 m2 g−1 (eBC), 5.83 m2 g−1 (NO3−), 5.69 m2 g−1 (low volatile organic aerosol), 2.78 m2 g−1 (SO42−), 2.40 m2 g−1 (hydrocarbon-like organic aerosol), and 1.04 m2 g−1 (semi volatile organic aerosol).

Abstract Malignant transformation and progression in cancer is associated with the altered expression of multiple miRNAs, which are considered as post-transcriptional regulators of genes participating in various cellular processes. Although, it has been proposed that miR-23b-3p acts as a tumor suppressor in cervical cancer (CC), not all the pathways through which it alters the cellular processes have been described. The present study examines whether miR-23b-3p directly represses the c-Met expression and that consequently modifies the proliferation, migration and invasion of C33A and CaSki cells. c-Met has five microRNA response elements (MREs) for miR-23b-3p in the 3′-UTR region. The ectopic overexpression of miR-23b-3p significantly reduces c-Met expression in C33A and CaSki cells. The overexpression of miR-23b-3p reduces proliferation, migration and invasion of CaSki cells and the proliferation and invasion in C33A cells. In CaSki cells, the activation of Gab1 and Fak, downstream of c-Met, is reduced in response to the overexpression of miR-23b-3p. Together, the results in the present study indicate that miR-23b-3p is a tumor suppressor that modulates the progression of CC via post-transcriptional regulation of the c-Met oncogene.

Abstract Background Gene expression profiles have demonstrated that miR-21 expression is altered in almost all types of cancers and it has been classified as an oncogenic microRNA. Persistent HPV infection is the main etiologic agent in cervical cancer and induces genetic instability, including disruption of microRNA gene expression. In the present study, we analyzed the underlying mechanism of how AP-1 transcription factor can active miR-21 gene expression in cervical cancer cells. Methods To identify that c-Fos and c-Jun regulate the expression of miR-21 we performed RT-qPCR and western blot assays. We analyzed the interaction of AP-1 with miR-21 promoter by EMSA and ChIP assays and determined the mechanism of its regulation by reporter construct plasmids. We identified the nuclear translocation of c-Fos and c-Jun by immunofluorescence microscopy assays. Results We demonstrated that c-Fos and c-Jun proteins are expressed and regulate the expression of miR-21 in cervical cancer cells. DNA sequence analysis revealed the presence of AP-1 DNA-binding sites in the human miR-21 promoter region. EMSA analyses confirmed the interactions of the miR-21 upstream transcription factor AP-1. ChIP assays further showed the binding of c-Fos to AP-1 sequences from the miR-21 core promoter in vivo. Functional analysis of AP-1 sequences of miR-21 in reporter plasmids demonstrated that these sequences increase the miR-21 promoter activation. Conclusions Our findings suggest a physical interaction and functional cooperation between AP-1 transcription factor in the miR-21 promoter and may explain the effect of AP-1 on miR-21 gene expression in cervical cancer cells.

Hypoxemia and oxidative stress, resulting in intrauterine growth restriction (IUGR) in undernourished twin sheep pregnancies, has been described in near-term studies. Our aim was to evaluate if the counteractive effects of maternal nutritional or antioxidant supplementation on the fetal redox status were evident before the accelerated fetal growth phase. Forty twin-bearing ewes grazing on natural Patagonian prairie were randomly assigned to four groups (n = 10 each; P: control ewes consuming mainly natural pasture; P+A: pasture plus antioxidants; P+C: pasture plus concentrate; P+A+C: pasture plus antioxidants and concentrate). Daily herbal antioxidants were supplemented in a feedstuff concentrate as a premix from day 35 until day 100 of gestation, when fetal venous cord blood samples and biometric measurements were obtained via cesarean section. The fetuses from group P were clearly hypoxemic. An analysis of variance showed that maternal antioxidant supplementation showed a trend of increased PO2, SatHb, and Ht, effects not observed in P+C fetuses. Antioxidants decreased the fetal MDA concentration (p < 0.05). Fetal TAC was increased by the antioxidants and concentrate (p < 0.05). Antioxidant supplementation showed a trend to increase fetal body weight but not biometry. The results suggest that negative effects of oxidative stress occur earlier than the overt growth arrest, and the maternal administration of antioxidants may constitute a good nutritional strategy for the early prevention of IUGR.

Autophagy is a highly conserved multistep lysosomal degradation process in which cellular components are localized to autophagosomes, which subsequently fuse with lysosomes to degrade the sequestered contents. Autophagy serves to maintain cellular homeostasis. There is a close relationship between autophagy and tumor progression, which provides opportunities for the development of anticancer therapeutics that target the autophagy pathway. In this review, we analyze the effects of human papillomavirus (HPV) E5, E6, and E7 oncoproteins on autophagy processes in cervical cancer development. Inhibition of the expression or the activity of E5, E6, and E7 can induce autophagy in cells expressing HPV oncogenes. Thus, E5, E6, and E7 oncoproteins target autophagy during HPV-associated carcinogenesis. Furthermore, noncoding RNA (ncRNA) expression profiling in cervical cancer has allowed the identification of autophagy-related ncRNAs associated with HPV. Autophagy-related genes are essential drivers of autophagy and are regulated by ncRNAs. We review the existing evidence regarding the role of autophagy-related proteins, the function of HPV E5, E6, and E7 oncoproteins, and the effects of noncoding RNA on autophagy regulation in the setting of cervical carcinogenesis. By characterizing the mechanisms behind the dysregulation of these critical factors and their impact on host cell autophagy, we advance understanding of the relationship between autophagy and progression from HPV infection to cervical cancer, and highlight pathways that can be targeted in preventive and therapeutic strategies against cervical cancer.

Black carbon (BC), a component of carbonaceous material, has an important role in the environment, and it is considered a short-lived climate forcer that plays a vital role in the global climate system. BC concentrations were analyzed during 2017 in two sites in Mexico, Juriquilla and Altzomoni, which have different emission sources and atmospheric dynamics. The annual average BC concentrations in 2017 were 0.84 ± 0.70 and 0.58 ± 0.37 µg m−3 for Juriquilla and Altzomoni, respectively. The principal contributors for the highest BC concentration in Juriquilla were anthropogenic sources, while pollutants transport from nearby cities was more important for Altzomoni. Comparison between this analysis and previous reports from 2015 for both sampling sites demonstrated an increase in BC concentration. Results of this study could contribute to a better understanding of BC effects under different emission conditions and provide a scientific reference for developing BC reduction strategies over Mexico.

Objective. To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. Materials and methods. Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative RealTime PCR assays. Results. Anthropometric and biochemical parameters were statistically higher in overweigth/ obese children (OW/O) than in lean (NW), Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. Conclusions. Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children.

We report estimations of the Mexicali Valley (Mexico) mixing height for three seasons. Surface and upper air meteorological measurements were carried out nearby Cerro Prieto geothermal power plant during July 2010 (summer), January 2012 (winter), and October 2016 (autumn). Four different methods were applied to estimate the convective boundary layer (CBL) height from radiosonde (RS) profiles: the parcel method, the gradients method, the least-squares variational approach based on the slab model of the CBL structure, and a covariance method. For nocturnal conditions, we used diagnostic models based on friction velocity and Monin–Obukhov length. Under unstable conditions, we obtained (on average) mixing heights of 497 m at 06:00 LST, 1242 m at 12:00 LST, 1404 m at 15:00 LST, and 482 at 18:00 LST during summer; 754 m at 12:00 LST during winter; and 1195 m at 12:00 LST and 13:00 m between the 14:00 and 15:00 LST during the autumn. The results allowed adjusting a semiempirical model to evaluate mixing height from turbulent sensible heat flux and friction velocity data. Our results provide practical tools that could facilitate the application of regulatory dispersion models to assess air quality in the region.

Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription–polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment.

Cervical cancer is one of the leading causes of death in women worldwide, which mainly affects developing countries. The patients who suffer a recurrence and/or progression disease have a higher risk of developing distal metastases. Proteases comprising the degradome given its ability to promote cell growth, migration, and invasion of tissues play an important role during tumor development and progression. In this study, we used high-density microarrays and quantitative reverse transcriptase polymerase chain reaction to evaluate the degradome profile and their inhibitors in 112 samples of patients diagnosed with locally advanced cervical cancer. Clinical follow-up was done during a period of 3 years. Using a correlation analysis between the response to treatment and the development of metastasis, we established a molecular signature comprising eight degradome-related genes (FAM111B, FAM111A, CFB, PSMB8, PSMB9, CASP7, PRSS16, and CD74) with the ability to discriminate patients at risk of distal metastases. In conclusion, present results show that molecular signature obtained from degradome genes can predict the possibility of metastasis in patients with locally advanced cervical cancer.

Cervical carcinoma (CC) is one of the most common cancers and a leading cause of mortality in women worldwide. Epidemiologic and experimental data have clearly demonstrated a causal role of high-risk Human Papillomavirus (HR-HPV) types in CC initiation and progression, affecting the cellular processes by targeting and inactivating p53 and pRB host proteins. HR-HPV E5, E6 and E7 oncoproteins have the ability to deregulate several cellular processes, mostly apoptosis, cell cycle control, migration, immune evasion, and induction of genetic instability, which promote the accumulation of mutations and aneuploidy. In this scenario, genomic profiles have shown that aberrant expression of cellular oncogenic and tumor suppressive miRNAs have an important role in CC carcinogenesis. It has been stated that HPV infection and E6/E7 expression are essential but not sufficient to lead to CC development; hence other genetic and epigenetic factors have to be involved in this complex disease. Recent evidence suggests an important level of interaction among E6/E7 viral proteins and cellular miRNA, and other noncoding RNAs. The aim of the current review is to analyze recent data that mainly describe the interaction between HR-HPV established infections and specific cellular miRNAs; moreover, to understand how those interactions could affect radio-therapeutic response in tumor cells.

Introducción. La hemorragia digestiva baja (HDB) masiva es un cuadro grave asociado a elevada mortalidad en pacientes hospitalizados con comorbilidades. Recientes publicaciones internacionales han destacado el rol de la embolización en el tratamiento de esta patología, aunque en Latinoamérica existe escasa experiencia. El objetivo de esta comunicación es describir una serie de casos tratados en la misma institución mediante embolización como tratamiento efectivo y seguro de la HDB masiva. Pacientes y métodos. Este es un estudio observacional descriptivo con inclusión prospectiva de pacientes con diagnostico clínico de HDB masiva, durante el período 2003-2009, en un hospital universitario de tercer nivel. La embolización fue realizada por cateterismo superselectivo luego de un abordaje percutáneo transfemoral. Resultados. Se incluyeron 26 pacientes (10 mujeres) con una edad media de 62 años (rango 2 a 92 años). Veinticinco (96%) pacientes tenían comorbilidades, incluyendo trastornos de la coagulación en 18 casos (69%). Todos los pacientes presentaron hematoquezia, hipotensión y/o shock hipovolémico con requerimiento transfusional de glóbulos rojos (media de 3,8 unidades, rango 2 a 12 unidades). La embolización fue efectiva para detener el sangrado en 24 pacientes (índice de éxito inmediato del 92%). No se observaron infartos digestivos ni complicaciones relacionadas al procedimiento. Conclusiones. La embolización superselectiva de la HDB masiva fue segura y efectiva en esta serie de pacientes. Se recomienda la embolización como tratamiento de elección para cohibir la HDB masiva en aquellos centros que cuenten con los recursos humanos y tecnológicos apropiados.

The “Aerosoles en Ciudad Universitaria 2015” (ACU15) campaign was an intensive experiment measuring chemical and optical properties of aerosols in the winter of 2015, from 19 January to 19 March on a site in the south of Mexico City. The mass concentration and chemical composition of the non-refractory submicron particulate matter (NR-PM1) was determined using an Aerodyne Aerosol Chemical Speciation Monitor (ACSM). The total NR-PM1 mass concentration measured was lower than reported in previous campaigns that took place north and east of the city. This difference might be explained by the natural variability of the atmospheric conditions, as well as the different sources impacting each site. However, the composition of the aerosol indicates that the aerosol is more aged (a larger fraction of the mass corresponds to sulfate and to low-volatility organic aerosol (LV-OOA)) in the south than the north and east areas; this is consistent with the location of the sources of PM and their precursors in the city, as well as the meteorological patterns usually observed in the metropolitan area.

La terapia génica es una excelente alternativa para el tratamiento de muchas enfermedades. La capacidad para manipular el DNA ha permitido dirigir la terapia génica para corregir la función de un gen alterado, aumentar la expresión de un gen o activar la respuesta inmune. Así, se puede proponer el uso del DNA como un medicamento capaz de controlar, corregir o curar una enfermedad. La terapia génica contra cáncer tiene un potencial enorme, y en la última década se han obtenido resultados muy alentadores del uso del DNA para controlar diversas neoplasias en modelos animales, lo cual ha permitido su aplicación en protocolos experimentales en humanos. Esta revisión concentra una reseña de los fundamentos de la terapia génica y su aplicación en cáncer cervical, desde el punto de vista de las alteraciones de la respuesta inmune enfocadas al microambiente tumoral y el uso de las citocinas como moduladores de la respuesta inmune.Gene therapy is an excellent alternative for treatment of many diseases. Capacity to manipulate the DNA has allowed direct the gene therapy to correct the function of an altered gene, to increase the expression of a gene and to favour the activation of the immune response. This way, it can intend the use of the DNA like medication able to control, to correct or to cure many diseases. Gene therapy against cancer has an enormous potential, and actually the use of the DNA has increased to control diverse cancer in animal models, with very encouraging results that have allowed its applications in experimental protocols in human. This work concentrates a review of the foundations of the gene therapy and its application on cervical cancer, from the point of view of the alterations of the immune system focused on the tumour micro-environment, and the use of the cytokines as immunomodulators.

El factor de crecimiento transformante beta-1 (TGF-beta1) es sintetizado por muchas estirpes celulares como linfocitos, macrófagos y células dendríticas, y su expresión regula de manera autócrina o parácrina la diferenciación, proliferación y el estado de activación de éstas y muchas otras células. En general, el TGF-beta1 tiene propiedades pleiotrópicas en el contexto de la respuesta inmune durante el desarrollo de infecciones y procesos neoplásicos; sin embargo, los mecanismos de acción y regulación de la expresión de esta citocina aún no se comprenden del todo. En la presente revisión se describen las propiedades biológicas y los procesos moleculares que regulan la expresión del TGF-beta1, para entender los efectos de esta citocina durante la proliferación y la diferenciación celular. El conocimiento de los mecanismos moleculares de la regulación del TGF-beta1 puede representar una importante estrategia de tratamiento del cáncer. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlTransforming growth factor beta-1 (TGF-beta1) is produced by several cell lineages such as lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these and other cells. In general, TGF-beta1 has pleiotropic properties on the immune response during the development of infection diseases and cancer; however, the mechanisms of action and regulation of gene expression of this cytokine are poorly understood, In this review, the biological properties and the molecular mechanisms that regulate TGF-beta1 gene expression are described, to understand the role of this cytokine in growth and cell differentiation. The knowledge of molecular mechanisms of gene expression of TGF-beta1 may serve to develop new cancer therapies. The English version of this paper is available at: http://www.insp.mx/salud/index.html

Durante el proceso de transformación de las células normales a células cancerosas, ocurren varias alteraciones genéticas. En este proceso se presenta la pérdida del control de los mecanismos de replicación y reparación del ADN, así como de la segregación del material genético. Aunque las células normales tienen estrategias de defensa contra el desarrollo del cáncer, las células tumorales activan diferentes vías de escape que permiten la progresión de la neoplasia. Avances recientes han permitido enfocar la investigación del cáncer hacia la identificación de algunos de sus factores etiológicos. El estudio del ciclo celular y su regulación han permitido conocer cómo la fidelidad y la integridad de la replicación del genoma son mantenidas por las funciones coordinadas de los puntos de control y de los sistemas de reparación del ADN. El funcionamiento adecuado de estos procesos puede ser alterado por mutaciones genéticas. Estos hallazgos sugieren que los mecanismos moleculares de regulación que participan en la transformación celular pueden ser empleados como sistemas potenciales para instrumentar nuevas terapias contra el desarrollo del cáncer.Several genetic alterations occur during the transformation process from normal to tumor cells, that involve the loss of fidelity of processes as replication, reparation, and segregation of the genomic material. Although normal cells have defense mechanisms against cancer progression, in tumor cells different escape pathways are activated leading to tumor progression. Recent advances have permitted cancer research to focus on the identification of some of its etiological factors. The knowledge of cell cycle reveals a precise mechanism achieved by the coordinated interactions and functions of cyclin-dependent kinases, control checkpoint, and repair pathways. Furthermore, it has been demonstrated that this coordinated function can be abrogated by specific genetic changes. These findings suggest that the molecular mechanisms responsible for cellular transformation may help to identify potential targets to improve cancer therapies.

Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

The ribonuclease Dicer plays a central role in the microRNA pathway by processing microRNA precursors (pre-microRNAs) into microRNAs, a class of 19- to 24-nucleotide non-coding RNAs that regulate expression of ≈60% of the genes in humans. To gain further insights into the function and regulation of Dicer in human cells, we performed a yeast two-hybrid (Y2HB) screen using human Dicer double-stranded RNA-binding domain (dsRBD) as bait. This approach identified tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as a Dicer-interacting protein candidate. Confocal immunofluorescence microscopy revealed the colocalization of Dicer and TWEAK proteins at the perinuclear region of HeLa cells. The Dicer-TWEAK protein interaction was confirmed by coimmunoprecipitation and found not likely to be mediated by RNA. TWEAK dose-dependently reduced pre-microRNA conversion into mature microRNA in Dicer activity assays using extracts of transfected human HEK 293 cells. TWEAK expression also impaired microRNA-guided RNA silencing of a reporter gene induced by a pre-microRNA. These findings suggest a role for TWEAK—a pro-inflammatory cytokine—in regulating Dicer function and microRNA biogenesis, and its possible involvement in regulating gene expression during inflammatory processes and diseases.