Differential Antibody Response against Conformational and Linear Epitopes of the L1 Proteins from Human Papillomavirus Types 16/18 Is Observed in Vaccinated Women or with Uterine Cervical Lesions.

Antibodies against the Human Papillomavirus (HPV) L1 protein are associated with past infections and related to the evolution of the disease, whereas antibodies against L1 Virus-Like Particles (VLPs) are used to follow the neutralizing antibody response in vaccinated women. In this study, serum antibodies against conformational (VLPs) and linear epitopes of HPV16/18 L1 protein were assessed to distinguish HPV-vaccinated women from those naturally infected or those with uterine cervical lesions. The VLPs-16/18 were generated in baculovirus, and L1 proteins were obtained from denatured VLPs. Serum antibodies against VLPs and L1 proteins were evaluated by ELISA. The ELISA-VLPs and ELISA-L1 16/18 assays were validated with a vaccinated women group by ROC analysis and the regression analysis to distinguish the different populations of female patients. The anti-VLPs-16/18 and anti-L1-16/18 antibodies effectively detect vaccinated women (AUC = 1.0/0.79, and 0.94/0.84, respectively). The regression analysis showed that anti-VLPs-16/18 and anti-L1-16/18 antibodies were associated with the vaccinated group (OR = 2.11 × 108/16.50 and 536.0/49.2, respectively). However, only the anti-L1-16 antibodies were associated with the high-grade lesions and cervical cancer (CIN3/CC) group (OR = 12.18). In conclusion, our results suggest that anti-VLPs-16/18 antibodies are effective and type-specific to detect HPV-vaccinated women, but anti-L1-16 antibodies better differentiate the CIN3/CC group. However, a larger population study is needed to validate these results.

Immune response and oxidative stress of shrimp Litopenaeus vannamei at different moon phases.

Moon phases influence the molting process of shrimp, which affect other physiological processes as immune response. This study analyzed some parameters of immune response: total hemocytes counts (THC), hemolymph clotting time and superoxide anion (O2-) production, total protein concentration, superoxide dismutase activity, and the presence of Vibrio spp. in Litopenaeus vannamei at different moon phases. The highest percentage of organisms in intermolt stage was observed in the first quarter moon phase (95%). The highest THC was observed at new moon phase, which was significantly different (p < 0.05) than that observed at the third quarter phase. Hemolymph clotting time and CFU values of Vibrio spp. showed no significant difference (p > 0.05) between different moon phases. The higher (p < 0.05) mean O2- production value (0.400 ± 0.168 nmol min-1 mL-1) was determined in hepatopancreas at new moon phase. No relationship was observed between O2- and SOD activity, indicating that this antioxidant response was enough to counteract the influence of oxidative stress in L. vannamei at different moon phases.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1ß and TNF-α were diminished after 10 days' treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Validation of Serological Antibody Profiles Against Human Papillomavirus Type 16 Antigens as Markers for Early Detection of Cervical Cancer.

Cervical cancer (CC) is the second most frequent neoplasia among women worldwide. Cancer prevention programs around the world have used the Papanicolaou (Pap) smear as the primary diagnostic test to reduce the burden of CC. Nevertheless, such programs have not been effective in developing countries, thus leading to research on alternative tests for CC screening. During the virus life cycle and in the process toward malignancy, different human papillomavirus (HPV) proteins are expressed, and they induce a host humoral immune response that can be used as a potential marker for different stages of the disease. We present a new Slot blot assay to detect serum antibodies against HPV16 E4, E7, and VLPs-L1 antigens. The system was validated with sera from a female population (n = 485) aged 18 to 64 years referred to the dysplasia clinic at the General Hospital in Cuautla, Morelos, Mexico. To evaluate the clinical performance of the serological markers, the sensitivity, specificity, positive, and negative predictive values and receiver-operating characteristic curves (for antibodies alone or in combination) were calculated in groups of lesions of increasing severity. The results showed high prevalence of anti-E4 (73%) and anti-E7 (80%) antibodies in the CC group. Seropositivity to 1, 2, or 3 antigens showed associations of increasing magnitude with CC (odds ratio [OR] = 12.6, 19.9, and 58.5, respectively). The highest association with CC was observed when the analysis was restricted to only anti-E4+E7 antibodies (OR = 187.7). The best clinical performance to discriminate CC from cervical intraepithelial neoplasia 2 to 3 was the one for the combination of anti-E4 and/or anti-E7 antibodies, which displayed high sensitivity (93.3%) and moderate specificity (64.1%), followed by anti-E4 and anti-E7 antibodies (73.3% and 80%; 89.6% and 66%, respectively). In addition, the sensitivity of anti-E4 and/or anti-E7 antibodies is high at any time of sexual activity (TSA), which suggests they can be biomarkers for the early detection of CC. The sensitivity of anti-E4 antibodies was low (<10%) when the TSA was <10 years, and it increased up to 100% in relation to the TSA, suggesting that anti-E4 antibodies can be useful as HPV exposure markers at early stages of the disease.

Humoral Immune Response Against Human Papillomavirus as Source of Biomarkers for the Prediction and Detection of Cervical Cancer.

Cervical cancer (CC) is one of the main causes of death among women of reproductive age. Although there are different tests, the disease tends to be diagnosed at late stages. In recent years, the use of complementary tests or sequential diagnostic tests has been implemented. Nevertheless, the results are variable and not conclusive; therefore, more studies for improving the usefulness of these tests in diagnostics are necessary. The human papillomavirus (HPV) infection has been associated with both benign and malignant proliferation of skin and mucosal tissues. Furthermore, some HPV types have been classified as high risk due to their potential to cause cancer, and HPV16 is most frequently associated with this disease. Although between 70% and 80% of precancerous lesions are eliminated by the host's immune system, there is no available test to distinguish between regressive lesions from those that could progress to CC. An HPV infection generates a humoral immune response against L1 and L2 capsid proteins, which can be protective and a response against early proteins. The latter is not a protective response, but these antibodies can be used as markers to determine the stage of the infection and/or the stage of the cervical lesion. Up to now, the humoral immune response resulting from the HPV infection has been used to study the biology of the virus and the efficacy of the HPV vaccines. Although there are no conclusive results regarding the use of these antibodies for diagnosis, we hereby review the actual panorama of the antibody response against the HPV proteins during the development of the disease as well as their possible use as biomarkers for the progression of cervical lesions and of CC.