Pllans-II: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient's quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans-II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5ß1 integrins and fibronectin of the extracellular matrix. Pllans-II reduces the cells' ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans-II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

Exploring the Safety of Pllans-II and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy.

The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 "Pllans-II," isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer.

Lipoxins and their relationship with inflammation-associated diseases. A systematic review.

AIM: To determine the relationship of lipoxin levels with inflammation and disease development in adults and children. METHODS: We conducted a systematic review. The search strategy included Medline, Ovid, EMBASE, LILACS, The Cochrane Central Register of Controlled Trials, and Open Gray. We included Clinical trials, cohort studies, case-control studies, and cross-sectional studies. Animal experiments were excluded. RESULTS: We included fourteen studies in this review, nine consistently showing decreased lipoxin levels and anti-inflammatory markers or increased pro-inflammatory markers in cardiovascular disease, metabolic syndrome, Alzheimer's disease, periodontitis, or autism. Five studies showed increased lipoxin levels and pro-inflammatory markers in pre-eclampsia, asthma, and coronary disease. On the other hand, one showed increased lipoxin levels and decreased pro-inflammatory marker levels. CONCLUSIONS: Decreases in lipoxins are associated with developing pathologies such as cardiovascular and neurological diseases, indicating that lipoxins protect against these pathologies. However, in other pathologies, such as asthma, pre-eclampsia, and periodontitis, which are associated with chronic inflammation despite increased levels of LXA4, the increase in inflammation suggests a possible failure of this regulatory pathway. Therefore, further studies are necessary to evaluate the role of LXA4 in the pathogenesis of inflammatory diseases.

Pllans-II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress.

Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line-Ca Ski-related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub-expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes' sub-expression at the protein level. In addition, Pllans-II presented a dose-dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans-II inhibited cancer cells' adhesion and migration capacity, induced cell cycle arrest in the G2/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans-II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.

Association between circulating microRNAs and the metabolic syndrome in adult populations: A systematic review.

BACKGROUND: Circulating microRNAs (miRNAs) are one of the most abundant classes of gene regulatory molecules, and had been associated to the metabolic syndrome, higher BMI, dyslipidemia and diabetes mellitus. In this sense, miRNAs could help to understand the mechanism behind the development of metabolic syndrome. OBJECTIVE: To determine the relationship between circulating microRNAs and the metabolic syndrome in adult population. METHODS: We performed a systematic review according to the recommendations of the Cochrane Collaboration and following the PRISMA Statement. The results were grouped for miRNAs levels in MetS and metabolic variables included in MetS and their statistic association with miRNAs levels. RESULTS: We finally included sixteen studies with a total of 7195 individuals. We found 47 miRNAs reported to be related to metabolic syndrome (p < 0,05) and 98 associated with the metabolic alterations included in its diagnostic (p < 0,05). Forty-nine miRNAs levels were described as relate to insulin resistance, 29 with high triglycerides, 35 with hypertension, 28 with obesity, and 16 miRNAs with cholesterol HDL(p < 0,05). Changes in levels of miR-505-5p, miR-148a-3p, miR-19b-3p, miR-320b, miR-342-3p, miR-197-3p, miR-192-5p, miR-122-5p, miR-103, miR-130a, miR-155-5p and miR-375, were reported as significant in more than one study. The results only included a descriptive synthesis, clinical heterogeneity did not allow a meta-analysis. CONCLUSION: The findings on the current systematic review suggests a possible relationship between miRNAs with metabolic syndrome and metabolic traits. This association could help to understand the mechanism behind the develop of the metabolic syndrome. However, more studies are necessary for further validation.

[Centile values for serum lipids in Colombian adolescents]. / Centiles de lípidos séricos en adolescentes de Colombia.

OBJECTIVE: To assess age- and sex-specific percentile baseline data for total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) in Colombian children and adolescents aged 10 to 17 years. PATIENTS AND METHODS: A cross-sectional, descriptive study was conducted on 1,773 children and adolescents. Each participant underwent a fasting measurement to quantify TC, HDL-C, and TG levels using enzymatic-colorimetric methods. Smoothed age- and sex-specific 5(th), 25(th), 50(th), 75(th), 90(th) and 95(th) percentile values where derived using LMS regression (Least Mean Square) using the statistical package Growth Analyzer. RESULTS: Overall, males had lower serum TC and TG levels as compared to females. P95 of TG and TC was higher in males aged 10 to 14 years as compared to females, while HDL-C levels were similar in both sexes. CONCLUSIONS: Percentile values will help classify children and adolescents as compared to other populations based on this health indicator.

Efecto del ejercicio físico aeróbico sobre el consumo de oxígeno de mujeres primigestantes saludables: estudio clínico aleatorizado / The effect of aerobic exercise on oxygen consumption in healthy firtst-pregnancy females: a randomized clinical trial

Objetivo: evaluar, en mujeres primigestantes saludables, el efecto del ejercicio aeróbico sobre el consumo de oxígeno. Materiales y métodos: estudio clínico aleatorizado en 64 mujeres saludables, primigestantes, entre 16 y 20 semanas de gestación. Grupo de intervención: ejercicio aeróbico entre el 50% y 65% de la frecuencia cardíaca máxima, durante 45 min, 3 veces por semana durante 16 semanas. Grupo control: actividad física habitual. Mediciones: consumo de oxígeno VO2max por prueba de caminata de seis minutos y antropometría para peso, talla y ganancia relativa de peso. Resultados: en las mediciones iniciales, no se encontraron diferencias entre grupos en ninguna de las variables. Al finalizar la intervención, las participantes que realizaron ejercicio presentaban una mayor capacidad física, medida por la distancia recorrida en el test de caminata (p=0,043) y por el VO2max (p=0,023). No se encontraron diferencias significativas entre los grupos en las variables antropométricas. Conclusión: la práctica regular de ejercicio aeróbico y controlado, mejora la capacidad física en mujeres gestantes. Por esta razón, intervenciones como esta podrían ser una alternativa temprana y efectiva para fortalecer la prevención de patologías durante el embarazo asociadas al sedentarismo.

Objective: evaluating the effect of aerobic exercise on oxygen consumption by healthy first-pregnancy females. Materials and methods: a randomized clinical trial was carried out on 64 healthy first-pregnancy females (16 to 20 weeks pregnant). Intervention group: aerobic exercise involving 50% to 65% maximum heart rate for 45 min, 3 times a week over a 16-week period. Control group: habitual physical activity. Measurements used: maximum oxygen consumption capacity test (VO2max) involving 6-minute walking test and anthropometric weight, height and relative weight gain indicators. Results: no differences were found in initial measurements between groups regarding any of the variables. By the end of the 16-week intervention, participants engaging in regular exercise presented greater physical capacity as measured by the distance covered in the walking (p=0.043) and VO2max (p=0.023) tests. No significant differences were found between groups regarding the anthropometric variables. Conclusion: engaging in regular controlled aerobic exercise improved physical capacity in pregnant females. Interventions like this could thus represent an early effective alternative for strengthening the prevention of physical inactivity pathologies during pregnancy.

Aerobic exercise during pregnancy improves health-related quality of life: a randomised trial.

QUESTION: Does supervised aerobic exercise during pregnancy improve health-related quality of life in nulliparous women? DESIGN: Analysis of secondary outcomes of a randomised trial with concealed allocation, blinded assessors, and intention-to-treat analysis. PARTICIPANTS: 64 nulliparous, pregnant women attending for prenatal care at one of three tertiary hospitals. INTERVENTION: The experimental group completed a 3-month supervised exercise program, commencing at 16 to 20 weeks of gestation. Each session included walking (10 min), aerobic exercise (30 min), stretching (10 min), and relaxation (10 min). The control group continued usual activities and performed no specific exercise. OUTCOME MEASURES: The primary outcome was health-related quality of life assessed by the Colombian version of the Medical Outcome Study Short-Form Health Survey at baseline and immediately after the 3-month intervention. RESULTS: Fifty women completed the study. After the 3-month intervention, the experimental group had improved their health-related quality of life more than the control group in the physical component summary of the questionnaire by 6 points (95% CI 2 to 11), the physical function domain (7 points, 95% CI 0 to 14), the bodily pain domain (7 points, 95% CI 1 to 13) and the general health domain (5 points, 95% CI 1 to 10). CONCLUSIONS: A supervised 3-month program of primarily aerobic exercise during pregnancy improves health-related quality of life. TRIAL REGISTRATION: NCT00741312.

Lipemia postprandial en adultos jóvenes de diferentes etnias en Colombia / Postprandial lipemia in Colombian young adults from different ethnias

La lipemia postprandial como factor asociado a aterogénesis esta con el desarrollo de Enfermedades Crónicas No Transmisibles (ECNT). Con el objetivo de determinar factores que modifican lipemia postprandial en respuesta a ingesta mixta de carbohidratos-lípidos en adultos jóvenes de diferentes etnias, se realizó estudio descriptivo no aleatorio con 51 sujetos (23.8±4 años) sanos, con registros de datos personales, clasificación étnica; Test Corto Insulina, Prueba de lipemia postprandial, cálculo de índice masa corporal (IMC) y Area Bajo la Curva (ABC) para evaluación postprandial. Alta porcentaje (80 por ciento) con antecedentes familiares de ECNT y sedentarismo. Los resultados mostraron promedios altos de ABC de glucosa, triglicéridos y Acidos Grasos No Esterificados (AGNE); el ABC de glucosa con diferencias por edad (p menor o igual 0.05), sin diferencias por etnia, género, IMC o sensibilidad a insulina. La curva de trigliceridemia mostró dos picos en mestizos (40 por ciento) y tres en negros (27 por ciento). Sujetos con patrón de cuatro picos tenían IMC elevado; igualmente fue mayor en blancos y mestizos que en negros (p<0.05); mayor en grupo mayores de 29 años y en hombres (p<0.05). El cambio de trigliceridemia sin diferencias por etnia, mayor en hombres (p<0.05) y en sujetos mayores (p<0.05). Correlación (r²= 0.70) entre IMC y trigliceridemia, entre IMC y cambio en trigliceridemia en etnias blancas y negra. Los AGNE descendieron hasta las 2 horas y a las 6-7h alcanzaron concentración mayor que la basal. ABC de Triglicéridos y AGNE mayores que lo reportado. Por alta correlación en casi todas las etnias IMC sería posible indicador de magnitud de trigliceridemia postprandial. Existe respuesta anormal a dieta de grasa, con liberación temprana de AGNE

[Postprandial lipemia in Colombian young adults from different ethnic groups]. / Lipemia postprandial en adultos jóvenes de diferentes etnias en Colombia.

Postprandial lipemia has been associated with atherogenesis and other non infectious chronic diseases. A descriptive, non aleatory study of 51 healthy young adults (23.8 +/- 4 years) of different ethnic background was carried out to identify possible personal or life style factors associated with the response of plasma lipids after a mixed carbohydrate and lipid load. Personal, family, life styles including use of drugs and activity and ethnic background were recorded. Anthropometrical measurements, a short insulin and postprandial lipemia tests were done. From these observations body mass index (BMI) and area under the curve (AUC) for lipids and glucose were calculated. High mean values were observed in AUC for glucose, triacylglycerol and nonesterified fatty acids (NEFA). Postprandial glucose with differences by age (p=0.05 Bonferroni) but no ethnic, gender, BMI or insulin sensitivity related significant differences were found. Mestizos (40%) showed two, and Negroes three (27%) postprandial triglyceridemia peaks. Noteworthy, subjects presenting four peaks had elevated BMI. Higher triglyceridemia values were found in white and mestizos (p<0.05), in subjects older than 29 and in males (p<0.05). Statistical correlation (r2=0.70) between BMI and triglyceridemia and change in postprandial trigliceridemia was found in white and black subjects. NEFA declined up to the second hour, but at 6-7 hours they reached levels higher than base values. Higher than reported values for UCA and BMI and an abnormal response to fat intake with an early release of NEFA was found. The high correlation between BMI and postprandial trigliceridemia suggests that body mass index could be a good predictor of postprandial trigliceridemia.