Relationship between the Viral Load in Patients with Different COVID-19 Severities and SARS-CoV-2 Variants.

SARS-CoV-2 has spread throughout the world since 2019, changing in its genome and leading to the appearance of new variants. This gave it different evolutionary advantages, such as greater infectivity and/or a greater ability to avoid the immune response, which could lead to an increased severity of COVID-19 cases. There is no consistent information about the viral load that occurs in infection with the different SARS-CoV-2 variants, hence, in this study we quantify the viral load of more than 16,800 samples taken from the Mexican population with confirmed diagnosis of COVID-19 and we analyze the relation between different demographic and disease variables. We detected that the viral load caused by different variants differs only in the first two days after the onset of symptoms, being higher when infections are caused by the delta variant and lower when caused by omicron. Furthermore, the viral load appears to be higher in outpatients compared to hospitalized patients or in cases of death. On the other hand, no differences were found in the viral load produced in vaccinated and unvaccinated patients, nor did it differ between genders.

Elimination of Human Papillomavirus and Cervical Pathological Microbiota with Photodynamic Therapy in Women from Mexico City with Cervical Intraepithelial Neoplasia I.

Cervical carcinoma (CC) is the second cause of cancer death in Mexican women. It starts with premalignant lesions known as Intraepithelial Cervical Neoplasia (CIN) that can develop due to infection by Human Papillomavirus (HPV) and other microorganisms. Current CIN therapy involves invasive methods that affect cervix integrity and fertility; we propose the use of photodynamic therapy (PDT) as a strategy with few side effects. In this work, the effectiveness of PDT for CIN I, HPV and pathogenic vaginal microbiota elimination in 29 women of Mexico City with CIN I, CIN I + HPV and HPV diagnosis was determined. After 6 months of PDT application, HPV infection was eliminated in 100% of the patients (P < 0.01), CIN I + HPV in 64.3% (P < 0.01) and CIN I in 57.2% (P > 0.05). PDT also eliminated pathogenic microorganisms: Chlamydia trachomatis in 81% of the women (P < 0.001) and Candida albicans in 80% (P < 0.05), without affecting normal microbiota since Lactobacillus iners was eliminated only in 5.8% of patients and the opportunistic Gardnerella vaginalis in 20%. These results show that PDT was highly effective in eradicating HPV and pathogenic microorganisms, suggesting that PDT is a promising therapy for cervical infections.

Longevity and Neutralizing Capacity of IgG Antibodies against SARS-CoV-2 Generated by the Application of BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac Vaccines: a Cohort Study in the Mexican Population.

The WHO has approved the use of several vaccines during the COVID-19 pandemic; experience over the last 2 years has indicated that dose demand can only be covered using more than one design. Therefore, having scientific evidence of the performance of the different vaccines applied in a country is highly relevant. In Mexico, 5 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were used, allowing a cohort study to analyze the generation of anti-S1/S2 IgG antibodies and anti-RBD antibodies with neutralizing activity at 0, 21, 90, and 180 days after vaccination. Five groups of participants were formed on the basis of the type of vaccine received and were divided on the basis of whether they previously had or did not have COVID-19. After completing the vaccination schedule, the seroprevalence was 95.5, 97.5, 81.0, 95.2, and 90.0% (BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac, respectively). Among the participants without COVID-19 prior to vaccination, the largest amount of antibodies in the 90-day period was observed in the BNT162b2 group, and the amount of antibodies in the Sputnik V group decreased the least over time. Even though the percentages of seroconversion obtained in this study were lower than those currently reported in other parts of the world, the tested vaccines are able, in most cases, to induce a good production of IgG antibodies anti-S1/S2 and neutralizing capacity. The fact that there are people who have not produced antibodies during the study leaves open some questions that must be investigated to avoid the appearance of serious cases of COVID-19. IMPORTANCE Since the start of the vaccination programs against COVID-19 in 2020, it was evident that due to global shortages, the demand for the dose required in Mexico could only be covered by acquiring different vaccines. Therefore, determining the effectiveness of these and the longevity of acquired immunity is extremely important in a scenario where SARS-CoV-2 circulation becomes endemic and booster doses are required periodically. Our data reveal significant differences both in the generation of antibodies as well as in their longevity for the vaccines applied in the country but suggest that, in general, the Mexican population can reach a high capacity to neutralize the virus, therefore, regarding less the variant for which they were designed.

Effective Capacitance from Equivalent Electrical Circuit as a Tool for Monitoring Non-Adherent Cell Suspensions at Low Frequencies.

Analyzing the electrical double layer (EDL) in electrical impedance spectroscopy (EIS) measurement at low frequencies remains a challenging task for sensing purposes. In this work, we propose two approaches to deal with the EDL in measuring impedance for particles and non-adherent cells in an electrolytic suspension. The first approach is a simple procedure to compute a normalized electrical impedance spectrum named dispersed medium index (DMi). The second is the EIS modeling through an equivalent electric circuit based on the so-called effective capacitance (Cef), which unifies the EDL phenomena. Firstly, as an experiment under controlled conditions, we examine polymer particles of 6, 15, and 48 µm in diameter suspended in a 0.9% sodium chloride solution. Subsequently, we used K-562 cells and leukocytes suspended in a culture medium (RPMI-1640 supplemented) for a biological assay. As the main result, the DMi is a function of the particle concentration. In addition, it shows a tendency with the particle size; regardless, it is limited to a volume fraction of 0.03 × 10-4 to 58 × 10-4. The DMi is not significantly different between K-562 cells and leukocytes for most concentrations. On the other hand, the Cef exhibits high applicability to retrieve a function that describes the concentration for each particle size, the K-562 cells, and leukocytes. The Cef also shows a tendency with the particle size without limitation within the range tested, and it allows distinction between the K-562 and leukocytes in the 25 cells/µL to 400 cells/µL range. We achieved a simple method for determining an Cef by unifying the parameters of an equivalent electrical circuit from data obtained with a conventional potentiostat. This simple approach is affordable for characterizing the population of non-adherent cells suspended in a cell culture medium.

Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231). METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm2. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry. RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF. CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery.

Nanoparticles (NPs) are novel platforms that can carry both cancer-targeting molecules and drugs to avoid severe side effects due to nonspecific drug delivery in standard chemotherapy treatments. Cancer cells are characterized by abnormal membranes, metabolic changes, the presence of lectin receptors, glucose transporters (GLUT) overexpression, and glycosylation of immune receptors of programmed death on cell surfaces. These characteristics have led to the development of several strategies for cancer therapy, including a large number of carbohydrate-modified NPs, which have become desirable for use in cell-selective drug delivery systems because they increase nanoparticle-cell interactions and uptake of carried drugs. Currently, the potential of NP glycosylation to enhance the safety and efficacy of carried therapeutic antitumor agents has been widely acknowledged, and much information is accumulating in this field. This review seeks to highlight recent advances in NP stabilization, toxicity reduction, and pharmacokinetic improvement and the promising potential of NP glycosylation from the perspective of molecular mechanisms described for drug delivery systems for cancer therapy. From preclinical proof-of-concept to demonstration of therapeutic value in the clinic, the challenges and opportunities presented by glycosylated NPs, with a focus on their applicability in the development of nanodrugs, are discussed in this review.

Use of AKR1C1 and TKTL1 in the Diagnosis of Low-grade Squamous Intraepithelial Lesions from Mexican Women.

BACKGROUND/AIM: To determine the differential protein profiles of cervical cancer cell lines in order to find potential targets that can be used as biomarkers in low-grade squamous intraepithelial lesions (LSIL) diagnosis. MATERIALS AND METHODS: Proteomic analysis was performed on cervical cancer cell lines by 2D electrophoresis and liquid chromatography-mass spectrometry. Biomarker validation was performed in histological samples by immunofluorescence. RESULTS: Aldo-keto reductase C1 (AKR1C1) and transketolase-like 1 (TKTL1) proteins were selected as biomarkers and their expression was increased in samples with LSIL diagnosis. TKTL1 in combination with AKR1C1 increased sensitivity and specificity to 75% and 66%, respectively, with an area under curve of 0.76 in receiver operating characteristics curve analysis. CONCLUSION: AKR1C1 and TKTL1 showed potential as biomarkers for diagnosis of LSIL in Mexican women, with similar sensitivity and specificity to the biomarkers used in clinical trials for diagnosis of LSIL.

CRISPR-dCas9-Based Artificial Transcription Factors to Improve Efficacy of Cancer Treatment With Drug Repurposing: Proposal for Future Research.

Due to the high resistance that cancer has shown to conventional therapies, it is difficult to treat this disease, particularly in advanced stages. In recent decades, treatments have been improved, being more specific according to the characteristics of the tumor, becoming more effective, less toxic, and invasive. Cancer can be treated by the combination of surgery, radiation therapy, and/or drug administration, but therapies based on anticancer drugs are the main cancer treatment. Cancer drug development requires long-time preclinical and clinical studies and is not cost-effective. Drug repurposing is an alternative for cancer therapies development since it is faster, safer, easier, cheaper, and repurposed drugs do not have serious side effects. However, cancer is a complex, heterogeneous, and highly dynamic disease with multiple evolving molecular constituents. This tumor heterogeneity causes several resistance mechanisms in cancer therapies, mainly the target mutation. The CRISPR-dCas9-based artificial transcription factors (ATFs) could be used in cancer therapy due to their possibility to manipulate DNA to modify target genes, activate tumor suppressor genes, silence oncogenes, and tumor resistance mechanisms for targeted therapy. In addition, drug repurposing combined with the use of CRISPR-dCas9-based ATFs could be an alternative cancer treatment to reduce cancer mortality. The aim of this review is to describe the potential of the repurposed drugs combined with CRISPR-dCas9-based ATFs to improve the efficacy of cancer treatment, discussing the possible advantages and disadvantages.

Gold nanoparticle uptake is enhanced by estradiol in MCF-7 breast cancer cells.

Purpose: In the present study, we investigated the effects of 17ß-estradiol (E2) on membrane roughness and gold nanoparticle (AuNP) uptake in MCF-7 breast cancer cells. Methods: Estrogen receptor (ER)-positive breast cancer cells (MCF-7) were exposed to bare 20 nm AuNPs in the presence and absence of 1×10-9 M E2 for different time intervals for up to 24 hrs. The effects of AuNP incorporation and E2 incubation on the MCF-7 cell surface roughness were measured using atomic force microscopy (AFM). Endocytic vesicle formation was studied using confocal laser scanning microscopy (CLSM). Finally, the results were confirmed by hyperspectral optical microscopy. Results: High-resolution AFM images of the surfaces of MCF-7 membranes (up to 250 nm2) were obtained. The incubation of cells for 12 hrs with AuNP and E2 increased the cell membrane roughness by 95% and 30% compared with the groups treated with vehicle (ethanol) or AuNPs only, respectively. This effect was blocked by an ER antagonist (7α,17ß-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol [ICI] 182,780). Higher amounts of AuNPs were localized inside MCF-7 cells around the nucleus, even after 6 hrs of E2 incubation, compared with vehicle-treated cells. Endolysosome formation was induced by E2, which may be associated with an increase in AuNP-uptake. Conclusions: E2 enhances AuNP incorporation in MCF-7 cells by modulating of plasma membrane roughness and inducing lysosomal endocytosis. These findings provide new insights into combined nanotherapies and hormone therapies for breast cancer.

Vaginosis-associated bacteria and its association with HPV infection. / Bacterias relacionadas con vaginosis bacteriana y su asociación a la infección por virus del papiloma humano.

BACKGROUND AND OBJECTIVE: Cervical cancer is an important health problem in our country. It is known that there are several risk factors for this neoplasm, and it has been suggested that cervical microbiome alterations could play a role in the development and progress of cancer. Bacterial vaginosis associated bacteria such as Atopobium vaginae and Gardnerella vaginalis has been suggested as potential risk factor for cervical lesions and cervical cancer. MATERIAL AND METHODS: DNA from 177 cervical scraping samples was studied: 104 belonged to women without cytological or colposcopic alterations and 73 samples from precursor lesions with previous human papillomavirus (HPV) infection history. All samples were screened for Atopobium vaginae, Gardnerella vaginalis and HPV by PCR. RESULTS: High HPV prevalence was found in precursor samples, and 30% of samples without lesions were positive for HPV. Virtually all samples contained sequences of both bacteria, and interestingly, there was not HPV association observed; these results could suggest that these microorganisms could be part of the cervical microbiome in Mexican population. CONCLUSIONS: The results obtained indicate that the bacteria analysed could be part of normal biome in Mexican women, suggesting a potential reconsideration of the pathogen role of these microorganisms.

Theranostic-PDT with the antibody anti isoform 4 SOD mitocondrial labeled with PpIX in the lung cancer cell line A-549.

BACKGROUND: In this work, a drug product composed of an IgM antibody derived from a hybridoma subclone 4C1F6D5G7B8 was prepared and further labeled with PpIX to be used in cell lines A-549 and MRC-5. The aim of this work was to evaluate the potential theranostic activity of the obtained product together with photodynamic therapy (PDT). METHODS: The IgM antibody labeled with PpIX was used in different concentrations to perform theranostics with PDT in cell lines A-549 and MRC-5 in order to identify the specificity of IgM antibody in lung cancer cells by means of a LED-irradiation system set at 630 nm. The location of the conjugate was further determined by confocal microscopy. RESULTS: The theranostic with conjugate Ab-PpIX in the A-549 cell lines showed fluorescence by confocal microscopy, whereas the MRC-5 cell line showed no reactivity. The PDT with the conjugate in the cell line A-549 decreased its viability 70% compared to the control. On the contrary, with the MRC-5 cell line no viability diference was shown. The confocal microscopy applied to the cell line A-549 showed that the Ab-PpIX was majorly located at the cytoplasm. CONCLUSION: Ab-PpIX showed therapeutical potential in lung cancer cells A-549 and had no activity in non-cancerous lung cells (MCR-5).

Effectiveness of Photodynamic Therapy in Elimination of HPV-16 and HPV-18 Associated with CIN I in Mexican Women.

This study aimed to determine the effectiveness of photodynamic therapy (PDT), using δ-aminolevulinic acid (5-ALA), in the elimination of premalignant cervical lesions in Mexican patients with human papillomavirus (HPV) infection and/or cervical intraepithelial neoplasia (CIN). Thirty women diagnosed with CIN I and/or positive for HPV participated in the study. Topical 6% 5-ALA in gel form was applied to the uterine cervix; after 4 h, the lesion area was irradiated with a light dose of 200 J cm-2 at 635 nm. This procedure was performed three times at 48-h intervals. Clinical follow-up was performed at 3, 6, and 12 months after the initial PDT administration, by colposcopy, cervical cytology, histopathological analysis, polymerase chain reaction, and hybrid capture. Of HPV-infected patients without evidence of CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although this response was not statistically significant. PDT using 6% 5-ALA is concluded to be effective in eliminating HPV infection associated or not with CIN I.

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential.

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

Antioxidant capacity and structural changes of human serum albumin from patients in advanced stages of diabetic nephropathy and the effect of the dialysis.

Changes in the antioxidant capacity of albumin and alterations of the albumin structural conformation were examined in patients in advanced stages of diabetes nephropathy. Human serum albumin was purified from diabetic patients in pre-dialysis (glomerular filtration rate [GFR] between 15 and 29 ml min(-1) 1.73 m(-2)) and those in dialysis (GFR ≤ 15 ml min(-1) 1.73 m(-2)) and then compared with albumin from patients with a normal GFR (>90 ml min(-1) m(-2)). We evaluated the antioxidant capacity of albumin using an enhanced chemiluminescence-based assay and thiol group content, and the structural changes were evaluated by circular dichroism and fluorescence spectroscopy. The antioxidant capacity and thiol content of albumin from patients in advanced stages of diabetic nephropathy were markedly reduced. The circular dichroism spectra showed a mean albumin α-helix content reduction from 44 to 37 % and from 44 to 30 % between the control group and pre-dialysis and dialysis patients, respectively. Additionally, the fluorescence intensity was reduced by 4.2 and 13 % for the groups 4 and 5, respectively, in relation with the control. These data provide evidence for the partial denaturation of albumin and exacerbated oxidative stress among patients in advanced stages of diabetes nephropathy before and even after dialysis.

[Use of nanoparticles (NP) in photodynamic therapy (PDT) against cancer]. / Uso de nanopartículas (NP) en la terapia fotodinámica (photodynamic therapy [PDT]) contra el cáncer.

Nanotechnology is a promising interdisciplinary field for developing improved methods of diagnosis and treatment of different diseases, including cancer. Give their optical, magnetic, and structural property, the nanoparticles have been proposed to be use in the development of unconventional treatments for cancer such as photodynamic therapy (PDT). In PDT, a photosensitizing agent is used that accumulates in tumor cells, generating reactive oxygen species that causes the death of malignant cells after irradiation with light at a particular wavelength. However, the use of PDT presents different problems in its application due to the characteristics of hydrophobicity of the photosensitizers, which hinder the efficiency of administration and treatment. It is here where the use of nanoparticles is proposed as a delivery vehicle to optimize treatment application. In this review we describe the use of nanoparticles coupled to PDT in the treatment of cancer and its molecular mechanism of action.

Effect of germinated soy protein on the growth of HeLa cervical cancer cells in female athymic mice.

Previous studies showed that germination could improve the antiproliferative effect of soy protein on cervical cancer cells and that a peptide fraction (MAPF) from germinated soybeans decreases the expression of PTTG1 and TOP2A (2 genes considered as therapeutic targets) causing apoptosis of cancer cells. The aim of this work was to study the effect of feeding germinated soybean protein diets on the tumor growth in nude mice inoculated with cervical cancer cells and identify the bioactive component. Mice were randomly assigned to 1 of the 6 dietary groups based in AIN-93G formulation with 6 protein sources: casein, ungerminated soy protein (SP), and SP from 2 and 6 days of germination, with and without ethanol-soluble phytochemicals (ESPC). Compared with casein-fed controls, the tumor volumes after 5 wk were reduced by 44.6% by ungerminated SP, 98.9% by 2-day-germinated SP, 97.7% by 2-day-germinated SP without ESPC, 94.7% by 6-day-germinated SP, and 92.7% by 6-day-germinated SP without ESPC (P < 0.05). Liquid chromatography coupled with tandem mass spectrometry analysis of MAPF showed that the bioactive peptide might be the leginsulin, a peptide involved in signal transduction of soybean cells. Germination is a simple procedure that could help to increase the anticancer activity of soy protein probably through generation of biologically active peptides.

Sodium butyrate increases the effect of the photodynamic therapy: a mechanism that involves modulation of gene expression and differentiation in astrocytoma cells.

OBJECTIVES: In order to evaluate the improvement of the photodynamic therapy (PDT) due to sodium butyrate (NaBu), its effectiveness in U373-MG and D54-MG astrocytoma cell lines was evaluated. METHODS: Cells were exposed to delta-aminolevulinic acid (δ-ALA) as a precursor to endogenous photosensitizer protoporphyrin IX (PpIX). In both astrocytoma cells, an important increase by ALA was observed in uroporphyrinogen synthetase gene expression: 1.8- and 52-fold for D54-MG and U373-MG cells, respectively. After irradiation, they showed 16.67 and 28.9% of mortality in U373-MG and D54-MG, respectively. These mortalities increased to 70.62 and 96.7% when U373-MG and D54-MG cells, respectively, were exposed 24 h to 8 mM NaBu, before to PpIX induction. NaBu induced expression of caspase-3, caspase-9, and Bcl-2 and increased Bax in U373-MG cells. ALA-induced morphological changes are compatible to differentiation. CONCLUSIONS: Genes and differentiation induced mainly by NaBu improve cell death performed by PDT in astrocytoma cells. These facts prove the synergistic effect of NaBu on cytotoxic damage induced by PDT.

Effect of ditaxin and heteranthin and inhibitory effect of Ditaxis heterantha extract on L5178Y tumor development in mice.

Ditaxis heterantha seeds are used as spices for flavoring and coloring food. Two new apocarotenoids derived from the seeds, heteranthin and ditaxin, were evaluated for their in vitro cytotoxic effects in murine lymphoma cells lines. Bioabsorption in mice and preventive and antitumor effects of the apocarotenoids were determined. Ditaxin and heteranthin showed cytotoxic effects in vitro against murine malignant cells and normal splenocyte cells. The 50% inhibitory concentration (IC(50)) for ditaxin in splenocytes was 0.1825 mM; in L5178Y, the IC(50) was 0.1923 mM. The heteranthin IC(50) in splenocytes was 0.1325 mM; in L5178Y, the value was 0.3889 mM. The maximum ditaxin plasma concentration was found after 2 hours of administration (mean±standard deviation, 7.5±2.05 µg/mL). Oral administration of the D. heterantha extract (100 mg/kg per day) for 14 days after the L5178Y lymphoma cell implantation showed no significant effect compared with groups that were not pretreated. However, tumor inhibition in groups treated intraperitoneally before inoculation with the L5178Y cells showed a significant difference (P<.001) compared with the groups not pretreated.

A COL2A1 gene polymorphism is related with advanced stages of osteoarthritis of the knee in Mexican Mestizo population.

Primary osteoarthritis (OA) is a multifactorial disease with several genetics factors involved. The COL2A1 gene is of particular interest because it encodes for the most abundant protein in articular cartilage. The aim was to evaluate the association of COL2A1 gene polymorphism with OA of the knee in Mexican Mestizo patients. A case-control study was conducted; cases comprised patients with a radiologic scoring > or = 2 and controls with a radiologic scoring <2. DNA was extracted from a peripheral blood sample, the polymorphic site of the COL2A1 gene was submitted to polymerase chain reaction (PCR), and the products were digested using PvuII restriction enzyme. For statistical analysis, a non-conditional logistic regression was developed. There were no associations among alleles in the overall sample, nevertheless, a significant association was found with p (Pp/pp) allele and OA of the knee grade 4 [odds ratio (OR), 95% confidence interval (CI 95%) 4.1 (1.2-14.6)] adjusted by gender, age, and body mass index (BMI). These results suggest an association of a COL2A1 gene polymorphism with advanced stages of OA of the knee in Mexican Mestizo population.

Spirulina maxima and its protein extract protect against hydroxyurea-teratogenic insult in mice.

Congenital malformations are one of the major causes of child mortality all over the world. In order to prevent them it is necessary to find substances that act as anti-teratogenic agents. In this study hydroxyurea (HU), an antineoplastic and teratogenic drug, was administered to pregnant mice because one of its major mechanisms of teratogenesis is the production of reactive oxygen species (ROS). The aim of this work was to determine if Spirulina maxima (SP) and its aqueous protein extract could protect against HU-teratogenic insult in mouse embryos. SP has been used for a long time because of its nutritional and pharmacological properties. The antioxidant activity, one of the most important, is related to the protein extract due to its content of phycobiliproteins. It was observed that neither SP nor its extract provoked teratogenic effects at any dose tested and even increased vitelline yolk sac circulation. Dams exposed to HU (30 mg/kg, i.p.) presented embryos with multiple alterations in their development. Groups treated with SP or its extract, before and after HU exposure, showed a protector effect in a dose-dependent manner. TBARS test confirmed that the protection effect was related to the antioxidant activity of both SP and its extract.