Heavy metal(loid)s contamination in water and sediments in a mining area in Ecuador: a comprehensive assessment for drinking water quality and human health risk.

Elevated heavy metal(loid)s concentrations in water lower its quality posing a threat to consumers. This study aims to assess the human health risk caused by heavy metal(loid)s in tap water in Santa Rosa city, Ecuador, and the ecological risk of stream water and sediments in the Santa Rosa River. Concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were evaluated in tap waters, stream waters, and sediment samples during the rainy and dry seasons. The Metal Index (MI), Geo-accumulation Index (Igeo), Potential Ecological Risk Index (PERI), and the levels of carcinogenic (CR) and non-carcinogenic risk (HQ) were determined. The results revealed severe pollution levels, mainly in Los Gringos and El Panteon streams, both tributaries of the Santa Rosa River, the primary water source for Santa Rosa inhabitants. More than 20% of the surface water samples showed severe contamination (MI > 6), and 90% of the tap water samples presented a MI value between 1 and 4, which indicates slight to moderate pollution. Drinking water displayed high levels of As, with 83% of the tap water samples collected from households in the dry season above the recommended concentration set by the World Health Organization and Ecuadorian legislation. The Igeo-Cd in the sediment samples was significantly high (Igeo > 3), and the PERI showed very high ecological risk (PERI > 600), with Cd as the main pollutant. HQ and CR were above the safe exposure threshold, suggesting that residents are at risk from tap water consumption, with As being the primary concern.

Mineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice.

INTRODUCTION AND OBJECTIVES: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. MATERIALS AND METHODS: C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. RESULTS: Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p < 0.05), and lower expression of pro-inflammatory and profibrotic markers compared to those mice fed a Low-Na+/HFD. Additionally, mice fed a High-Na+/HFD showed higher expression of salt-inducible kinase (SIK)-1 and lower expression of serum-and-glucocorticoid-inducible kinase (SGK)-1. Similar results were observed with the MCD diet model. CONCLUSION: We identified in two experimental models of NAFLD that High-Na+ diet content is associated to lower serum aldosterone levels and hepatic MR downregulation, associated to decreased steatosis and reduced de novo hepatic lipogenesis, proinflammatory and profibrotic markers. Decreased activation of hepatic MR seems to generate beneficial downstream inhibition of lipogenesis in experimental NAFLD.

Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12.

BACKGROUND & AIMS: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. METHODS: Mice with HSC-selective deletion of NRP (ColCre/Nrp1loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1loxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. RESULTS: ColCre/Nrp1loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/Nrp1loxP mice compared to supernatant from Nrp1loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. CONCLUSION: Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. LAY SUMMARY: Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.

A dysfunctional family environment and a high body fat percentage negatively affect telomere length in Mexican boys aged 8-10 years.

AIM: The aim of this study was to determine whether a direct relationship existed between absolute telomere length (aTL), obesity and familial functionality in a group of Mexican children. METHODS: We recruited 134 children (52% boys) aged 8-10 years during regular primary care check-ups in 2016 and evaluated physical activity (PA), feeding practices, anthropometrics, body fat percentage (BF%) and family dysfunction. Optimised quantitative PCR determined aTL from genomic deoxyribonucleic acid isolated from saliva samples. RESULTS: Boys with a healthy BF% showed a higher aTL than their high BF% counterparts (P < .01). aTL was higher in children who performed PA than their sedentary counterparts (P < .05). Alarmingly, 90% of the children belonged to dysfunctional families and a dysfunctional family was correlated with a higher BF% (r = -.57). Negative correlations between the BF% and aTL (r = -.1765) and the BF% and time dedicated to PA (r = -.031) were observed in boys. On the contrary, we found a positive correlation between the aTL and weekly PA (r = .1938). These correlations were not observed in girls. CONCLUSION: Telomere shortening was associated with a high BF% in boys, but not girls. Dysfunctional families were also a key factor. School PA programmes should be mandatory.

Whole-body MRI for staging and interim response monitoring in paediatric and adolescent Hodgkin's lymphoma: a comparison with multi-modality reference standard including 18F-FDG-PET-CT.

OBJECTIVES: To prospectively investigate concordance between whole-body MRI (WB-MRI) and a composite reference standard for initial staging and interim response evaluation in paediatric and adolescent Hodgkin's lymphoma. METHODS: Fifty patients (32 male, age range 6-19 years) underwent WB-MRI and standard investigations, including 18F-FDG-PET-CT at diagnosis and following 2-3 chemotherapy cycles. Two radiologists in consensus interpreted WB-MRI using prespecified definitions of disease positivity. A third radiologist reviewed a subset of staging WB-MRIs (n = 38) separately to test for interobserver agreement. A multidisciplinary team derived a primary reference standard using all available imaging/clinical investigations. Subsequently, a second multidisciplinary panel rereviewed all imaging with long-term follow-up data to derive an enhanced reference standard. Interobserver agreement for WB-MRI reads was tested using kappa statistics. Concordance for correct classification of all disease sites, true positive rate (TPR), false positive rate (FPR) and kappa for staging/response agreement were calculated for WB-MRI. RESULTS: There was discordance for full stage in 74% (95% CI 61.9-83.9%) and 44% (32.0-56.6%) of patients against the primary and enhanced reference standards, respectively. Against the enhanced reference standard, the WB-MRI TPR, FPR and kappa were 91%, 1% and 0.93 (0.90-0.96) for nodal disease and 79%, < 1% and 0.86 (0.77-0.95) for extra-nodal disease. WB-MRI response classification was correct in 25/38 evaluable patients (66%), underestimating response in 26% (kappa 0.30, 95% CI 0.04-0.57). There was a good agreement for nodal (kappa 0.78, 95% CI 0.73-0.84) and extra-nodal staging (kappa 0.60, 95% CI 0.41-0.78) between WB-MRI reads CONCLUSIONS: WB-MRI has reasonable accuracy for nodal and extra-nodal staging but is discordant with standard imaging in a substantial minority of patients, and tends to underestimate disease response. KEY POINTS: • This prospective single-centre study showed discordance for full patient staging of 44% between WB-MRI and a multi-modality reference standard in paediatric and adolescent Hodgkin's lymphoma. • WB-MRI underestimates interim disease response in paediatric and adolescent Hodgkin's lymphoma. • WB-MRI shows promise in paediatric and adolescent Hodgkin's lymphoma but currently cannot replace conventional staging pathways including 18F-FDG-PET-CT.

Adipose tissue IL-18 production is independent of caspase-1 and caspase-11.

BACKGROUND: Inflammation in adipose tissue, resulting from imbalanced caloric intake and energy expenditure, contributes to the metabolic dysregulation observed in obesity. The production of inflammatory cytokines, such as IL-1ß and IL-18, plays a key role in this process. While IL-1ß promotes insulin resistance and diabetes, IL-18 regulates energy expenditure and food intake. Previous studies have suggested that caspase-1, activated by the Nlrp3 inflammasome in response to lipid excess, mediates IL-1ß production, whereas activated by the Nlrp1b inflammasome in response to energy excess, mediates IL-18 production. However, this has not been formally tested. METHODS: Wild-type and caspase-1-deficient Balb/c mice, carrying the Nlrp1b1 allele, were fed with regular chow or a high-fat diet for twelve weeks. Food intake and mass gain were recorded weekly. At the end of the twelve weeks, glucose tolerance and insulin resistance were evaluated. Mature IL-18 protein levels and the inflammatory process in the adipose tissue were determined. Fasting lipid and cytokine levels were quantified in the sera of the different experimental groups. RESULTS: We found that IL-18 production in adipose tissue is independent of caspase-1 activity, regardless of the metabolic state, while Nlrp3-mediated IL-1ß production remains caspase-1 dependent. Additionally, caspase-1 null Balb/c mice did not develop metabolic abnormalities in response to energy excess from the high-fat diet. CONCLUSION: Our findings suggest that IL-18 production in the adipose tissue is independent of Nlrp3 inflammasome and caspase-1 activation, regardless of caloric food intake. In contrast, Nlrp3-mediated IL-1ß production is caspase-1 dependent. These results provide new insights into the mechanisms underlying cytokine production in the adipose tissue during both homeostatic conditions and metabolic stress, highlighting the distinct roles of caspase-1 and the Nlrp inflammasomes in regulating inflammatory responses.

Evaluation of stress tolerance and design of alternative culture media for the production of fermentation starter cultures in cacao.

Ecuador is one of the world's leading producers of cacao beans, and Nacional x Trinitario cacao represents one of the most distinctive varieties due to its flavor and aroma characteristics. This study aimed to evaluate the effect of the starter culture isolated from microbial diversity during the spontaneous fermentation of Nacional x Trinitario cacao. A total of 249 microbial isolates were obtained from spontaneous culture, with Lactiplantibacillus (45 %), Saccharomyces (17 %), and Acetobacter (2 %) being the most relevant genera for fermentation. Tolerance tests were conducted to select microorganisms for the starter culture. Lactiplantibacillus plantarum exhibited the highest tolerance at pH 5 and 6 % ethanol and tolerated concentrations up to 15 % for glucose and fructose. Acetobacter pasteurianus grew at pH 2 and 6 % ethanol, tolerating high sugar concentrations of up to 15 % for glucose and 30 % for fructose, with growth observed in concentrations up to 5 % for lactic and acetic acid. Subsequently, a laboratory-scale fermentation was conducted with the formulated starter culture (SC) comprising S. cerevisiae, L. plantarum, and A. pasteurianus, which exhibited high tolerance to various stress conditions. The fermentation increased alcoholic compounds, including citrusy, fruity aromas, and floral notes such as 2-heptanol and phenylethyl alcohol, respectively 1.6-fold and 5.6-fold compared to the control. Moreover, the abundance of ketones 2-heptanone and 2-nonanone increased significantly, providing sweet green herbs and fruity woody aromas. Cacao fermented with this SC significantly enhanced the favorable aroma-producing metabolites characteristic of Fine-aroma cacao. These findings underscore the potential of tailored fermentation strategies to improve cacao product quality and sensory attributes, emphasizing the importance of ongoing research in optimizing fermentation processes for the cacao industry.

Incidence of thrombosis in adults with acute leukemia: a single center experience in Mexico.

BACKGROUND: Acute leukemias are hematopoietic malignancies that may be accompanied by hemostatic abnormalities. In general, information on the frequency of thrombotic events, their clinical characteristics and survival in adult patients with acute leukemia is still scarce and controversial. OBJECTIVES: To describe the frequency of thrombotic events, their clinical characteristics and survival of adult patients with acute leukemia at the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City. MATERIAL AND METHODS: A patient cohort, diagnosed and treated between October 2003 and December 2009, was retrospectively analyzed in terms of thrombotic events, frequencies and survival curves. RESULTS: We analyzed 181 patients with a median age of 33 years, 80 were female (44.2%). Fifteen cases with thrombosis (8.3%) were documented and in 53.3% of cases, they were related to the use of a central venous catheter. The median time to development of thrombosis was 92 days; 33.3% of events occurred during the first 30 days after diagnosis. The incidence of thrombosis in patients receiving L-asparaginase was 15%. Of the 15 patients with thrombosis, 27% were alive and without evidence of disease at last follow-up, and 73% had died; disease progression was the most common cause of death (81.8%). None of the thrombotic events had an impact on mortality. Median overall survival (OS) was 349 days. CONCLUSIONS: The incidence of thrombosis in this adult acute leukemia population is comparable to that reported in the literature. Only a third of cases occurred during the first month after diagnosis; however, 93.3% of patients developed a thrombotic event during the first year after the diagnosis of acute leukemia. All cases were symptomatic and central venous catheter-related thrombosis was the most frequent presentation in this group. Survival curves comparing patients with and without thrombosis were similar. Prospective studies are necessary in order to assess the risk factors fostering thrombosis in adult patients with acute leukemia.

Conventional and non-conventional disinfection methods to prevent microbial contamination in minimally processed fruits and vegetables.

Pandemic COVID-19 warned the importance of preparing the immune system to prevent diseases. Therefore, consuming fresh fruits and vegetables is essential for a healthy and balanced diet due to their diverse compositions of vitamins, minerals, fiber, and bioactive compounds. However, these fresh products grew close to manure and irrigation water and are harvested with equipment or by hand, representing a high risk of microbial, physical, and chemical contamination. The handling of fruits and vegetables exposed them to various wet surfaces of equipment and utensils, an ideal environment for biofilm formation and a potential risk for microbial contamination and foodborne illnesses. In this sense, this review presents an overview of the main problems associated with microbial contamination and the several chemicals, physical, and biological disinfection methods concerning their ability to avoid food contamination. This work has discussed using chemical products such as chlorine compounds, peroxyacetic acid, and quaternary ammonium compounds. Moreover, newer techniques including ozone, electrolyzed water, ultraviolet light, ultrasound, high hydrostatic pressure, cold plasma technology, and microbial surfactants have also been illustrated here. Finally, future trends in disinfection with a sustainable approach such as combined methods were also described. Therefore, the fruit and vegetable industries can be informed about their main microbial risks to establish optimal and efficient procedures to ensure food safety.

Biosurfactant from Bacillus subtilis DS03: Properties and Application in Cleaning Out Place System in a Pilot Sausages Processing.

Biosurfactants (BS) are amphiphilic molecules that align at the interface reducing the surface tension. BS production is developed as an alternative to synthetic surfactants because they are biodegradable, with low toxicity and high specificity. BS are versatile, and this research proposes using a biosurfactant crude extract (BCE) as part of cleaning products. This paper reported the BCE production from Bacillus subtilis DS03 using a medium with molasses. The BCE product was characterized by different physical and chemical tests under a wide pH range, high temperatures, and emulsifying properties showing successful results. The water surface tension of 72 mN/m was reduced to 34 mN/m with BCE, achieving a critical micelle concentration at 24.66 ppm. BCE was also applied to polystyrene surface as pre-treatment to avoid microbial biofilm development, showing inhibition in more than 90% of Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes above 2000 ppm BCE. The test continued using BCE as post-treatment to remove biofilms, reporting a significant reduction of 50.10% Escherichia coli, 55.77% Staphylococcus aureus, and 59.44% Listeria monocytogenes in a concentration higher than 250 ppm BCE. Finally, a comparison experiment was performed between sodium lauryl ether sulfate (SLES) and BCE (included in commercial formulation), reporting an efficient reduction with the mixtures. The results suggested that BCE is a promising ingredient for cleaning formulations with applications in industrial food applications.

Comparison of three different COVID-19 vaccine platforms (CoronaVac, BTN162b2, and Ad5-nCoV) in individuals with and without prior COVID-19: Reactogenicity and neutralizing antibodies.

Neutralizing antibodies (NAbs) can be indicators of collective immunity, vaccine efficacy, and the longevity of the humoral response. This study aimed to compare reactogenicity and NAbs generated by three different COVID-19 vaccine platforms in individuals with and without prior COVID-19. 336 individuals vaccinated (112 with CoronaVac [inactivated virus], 112 with BNT162b2 [messenger RNA], and 112 with Ad5-nCoV [non-replicating viral vector]) were included. NAbs were quantified with the cPass SARS-CoV-2 kit. Individuals immunized with the Ad5-nCoV showed higher reactogenicity than those immunized with the other vaccines (p < 0.001). The BTN162b2 vaccine-induced NAbs with higher inhibition capacity than the other platforms in the first dose. In individuals without prior COVID-19, the Ad5-nCoV vaccine generated lower NAbs against SARS-CoV-2 than those induced by two doses of the BTN162b2 (Ad5-nCoV 72.10 [55.6-93.4] vs. BTN162b2 98.41 [98.16-98.56], p < 0.0001). One individual did not generate NAbs (0.89%) after a complete immunization with CoronaVac; in BTN162b2, all generated these antibodies, and in the Ad5-nCoV group, four individuals (3.57%) did not generate NAbs. Comorbidities, gender, age, and reactogenicity did not significantly influence the generation of NAbs (p > 0.05); however, a history of COVID-19 before vaccination was associated with antibodies with greater neutralizing capacity after the first dose (p < 0.01). In conclusion, the mRNA vaccine (BTN162b2) had a remarkable better ability to produce NAbs and lower reactogenicity than the other platforms, whereas the Ad5-nCov vaccine induced the lowest NAbs response in individuals without a history of COVID-19; therefore, we suggest that a booster could benefit these individuals.

An enriched environment re-establishes metabolic homeostasis by reducing obesity-induced inflammation.

Obesity can lead to chronic inflammation in different tissues, generating insulin and leptin resistance and alterations in glucose and lipid metabolism, favoring the development of degenerative diseases, including type II diabetes. Congruently, the inflammatory signaling inhibition prevents the development of obesity and restores insulin sensitivity. Via the enhancement of central nervous system activity, an enriched environment (EE) has beneficial effects on learning and memory as well as on immune cell functions and inflammation in different disease models. Here, we explored whether an EE can restore energy balance in obese mice that previously presented metabolic alterations. We discovered that an EE improved glucose metabolism, increased insulin signaling in liver, and reduced hepatic steatosis and inflammation, and increased lipolysis and browning in the white adipose tissue of high-fat diet (HFD)-fed mice. Finally, we found reduced inflammatory signaling and increased anorexigenic signaling in the hypothalamus of HFD-fed mice exposed to an EE. These data indicate that an EE is able to restore the metabolic imbalance caused by HFD feeding. Thus, we propose EE as a novel therapeutic approach for treating obesity-related metabolic alterations. This article has an associated First Person interview with the first author of the paper.

Nlrp1b1 negatively modulates obesity-induced inflammation by promoting IL-18 production.

Obesity-induced inflammation, triggered by lipid-mediated activation of the Nlrp3 inflammasome, results in glucose metabolism alterations and type 2 diabetes. This knowledge has been generated using animals deficient for any of the different components of this inflammasome (Caspase-1, Asc or Nlrp3) in the C57BL/6 background. Unlike C57BL/6 mice, which carry allele 2 of the Nlrp1b gene (Nlrp1b2), Balb/c mice that carry allele 1 (Nlrp1b1) are less prone to develop alterations in the glucose metabolism when fed with a high fat diet. However, the molecular bases for these metabolic differences are unknown. Here we show that the Nlrp1b1 allele down regulates the adipose tissue inflammatory response attenuating glucose intolerance and insulin resistance in obese C57BL/mice. Our results indicate that the positive effects of the Nlrp1b1 inflammasome on glucose tolerance and insulin sensitivity involve IL-18-mediated effects on lipolysis, pointing out that differential expression of allelic variants of genes coding for inflammasome components might control susceptibility or resistance to develop diabetes in obese individuals.

Lichenysin-geminal amino acid-based surfactants: Synergistic action of an unconventional antimicrobial mixture.

Recently it has been demonstrated that catanionic mixtures of oppositely charged surfactants have improved physicochemical-biological properties compared to the individual components. Isotherms of mixtures of an anionic biosurfactant (lichenysin) and a cationic aminoacid surfactant (C3(LA)2) indicate a strong interaction suggesting the formation of a new "pseudo-surfactant". The antimicrobial properties of the mixture lichenysin and C3(LA)2 M80:20, indicate a synergistic effect of the components. The mechanism of action on the bacterial envelope was assessed by flow cytometry and Transmission Electron Microscopy.

Purification and identification of Bacillus subtilis SPB1 lipopeptide biosurfactant exhibiting antifungal activity against Rhizoctonia bataticola and Rhizoctonia solani.

This study reports the potential of a soil bacterium, Bacillus subtilis strain SPB1, to produce lipopeptide biosurfactants. Firstly, the crude lipopeptide mixture was tested for its inhibitory activity against phytopathogenic fungi. A minimal inhibitory concentration (MIC), an inhibitory concentration at 50% (IC50%), and an inhibitory concentration at 90% (IC90%) values were determined to be 0.04, 0.012, and 0.02 mg/ml, respectively, for Rhizoctonia bataticola with a fungistatic mode of action. For Rhizoctonia solani, a MIC, an IC50%, and IC90% values were determined to be 4, 0.25, and 3.3 mg/ml, respectively, with a fungicidal mode of action. For both of the fungi, a loss of sclerotial integrity, granulation and fragmentation of hyphal mycelia, followed by hyphal shriveling and cell lysis were observed with the treatment with SPB1 biosurfactant fraction. After extraction, separation, and purification, different lipopeptide compounds were identified in the culture filtrate of strain SPB1. Mass spectroscopic analysis confirmed the presence of different lipopeptide compounds consisting of surfactin isoforms with molecular weights of 1007, 1021, and 1035 Da; iturin isoforms with molecular weights of 1028, 1042, and 1056 Da; and fengycin isoforms with molecular weights of 1432 and 1446 Da. Two new clusters of lipopeptide isoforms with molecular weights of 1410 and 1424 Da and 973 and 987 Da, respectively, were also detected. This study reported the ability of a B. subtilis strain to co-produce lipopeptide isoforms with potential use as antifungal compounds.

Targeted treatments for cervical cancer: a review.

Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%-95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development.