Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease.

BACKGROUND: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. METHODS: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. RESULTS: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. CONCLUSIONS: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.

Multidrug-resistant Raoultella ornithinolytica misidentified as Klebsiella oxytoca carrying blaOXA ß-lactamases: antimicrobial profile and genomic characterization.

Class D ß-lactamases OXA-232 and OXA-48 hydrolyze penicillin, cephalosporins and carbapenems, limiting the pharmacological therapeutics in bacteraemia. OXA producer microorganisms are considered a great emergent threat, especially in nosocomial environments. To determine the resistance profile and genomic characterization of two isolates initially identified as potential carbapenemase-producer Klebsiella oxytoca in a third level hospital. Automated platform BD Phoenix-100 System was used to identify and to biochemically characterize both isolates. Furthermore, the resistance profile was determined through CLSI methods and the whole genome sequences were obtained using Next-Generation Sequencing. Resistance genes were analyzed, and the virtual fingerprinting was determined to corroborate the similarity with related bacteria. Both strains correspond to Raoultella ornithinolytica carrying OXA 232 and OXA-48 genes, confirming the class D ß-lactamases assay results. Here, we present the genetic and phenotypic analysis of multidrug resistance R. ornithinolytica, representing the first report in Mexico.

Complete genome sequence of a coxsackievirus type A24 variant causing an outbreak of acute haemorrhagic conjunctivitis in southeastern Mexico in 2017.

Cases of acute haemorrhagic conjunctivitis (AHC) caused by a coxsackie virus A24 variant (CV-A24v) in Mexico have been reported since 1987; however, no molecular data on the causative strains have been available. Here, we report the identification of the etiological agent responsible for the most recent AHC outbreak in southeastern Mexico (at the end of 2017) as well as the complete genome sequences of seven isolates, using next-generation sequencing (NGS). Phylogenomic analysis of the CV-A24v sequences reported here showed similarity to contemporary strains causing AHC outbreaks in French Guiana and Uganda, forming a novel clade related to genotype IV. Moreover, a specific mutational pattern in the non-structural proteins was identified in the 2017 isolates. This is the first report of genetic characterization of CV-A24v isolates obtained in Mexico.

Full genome sequence of the first SARS-CoV-2 detected in Mexico.

SARS-CoV-2 was first detected in the city of Wuhan, Hubei Province, China. In this report, we describe the complete genome sequence of the first imported SARS-CoV-2, detected in a Mexican patient who had traveled to Bergamo, Italy. Phylogenetic analysis showed that this isolate belongs to subclade A2a (lineage G) and is closely related to isolates from Finland, Germany and Brazil, all of which were from patients with a history of travel to Italy. This is the first report of the complete genome sequence of this virus in Mexico.

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist of a heterocomplex between the erythropoietin receptor (EPOR) and the beta common receptor (ßcR). The present study explored the effects of rEPO to prevent renal fibrosis in adenine-induced chronic kidney disease (Ad-CKD) and their association with the expression of the heterodimer EPOR/ßcR. Male Wistar rats were randomized to control group (CTL), adenine-fed rats (Ad-CKD), and Ad-CKD with treatment of rEPO (1050 IU/kg, once weekly for 4 weeks). Ad-CKD rats exhibited anemia, uremia, decreased renal function, increased infiltration of inflammatory cells, tubular atrophy, and fibrosis. rEPO treatment not only corrected anemia but reduced uremia and partially improved renal function as well. In addition, we observed that rEPO diminishes tubular injury, prevents fibrosis deposition, and induces the EPOR/ßcR heteroreceptor. The findings may explain the extrahematopoietic effects of rEPO in CKD and provide new strategies for the treatment of renal fibrosis in CKD.

Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples.

Human papillomavirus genotype 16 (HPV16) is the most frequent high-risk HPV (HR-HPV) identified in cervical precursor lesions and cervical cancer (CC) worldwide. The oncogenic potential of HPV16 is partly dependent on the lineage involved in the infection and the presence of clinically relevant mutations. In this report, we present the distribution of HR-HPV and the mutational profile and intra-host variability of HPV16 lineages, based on analysis of the long control region (LCR) and the E6 gene in samples with normal cytology (n = 39), squamous intraepithelial lesions (n = 25), and CC (n = 39). HR-HPV genotyping was performed using multiplex real-time PCR. HPV16 lineage assignments and mutation frequencies were determined by conventional PCR and Sanger DNA sequencing, and intra-patient viral populations were analyzed using next-generation sequencing (NGS). The most frequent HR-HPV type was HPV16, followed by HPV31 and HPV18. The frequency of HPV16 sublineages was A1/A2 > D2 > D3 and B1. Moreover, the most frequent mutations, both in samples from this study and in the available sequences from Mexican isolates in the GenBank database were LCR-G7518A, which is involved in carcinogenesis, and E6-T350G (producing L83V), associated with persistence of infection. Otherwise, deep sequencing revealed high conservation of viral lineages and mutations, independently of the stages studied. In conclusion, the high frequency and stability of these molecular markers, as well as the circulating viral lineages, could be related to the incidence of CC associated with HPV16. Hence, they deserve a broader analysis to determine the risk of specific populations for progression of the disease.

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration.

BACKGROUND: The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. METHODS: This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar) treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC), and polyamine levels, were determined. RESULTS: Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also "synchronized" by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. CONCLUSIONS: Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased retinoid levels induced by α-tocopherol. Therefore interactions between polyamines and retinol, mediated by the oxidant status, should be taken into consideration in the development of new therapeutic strategies for pathologies occurring with liver cell proliferation.

Anti-Drug Antibodies in the Biological Therapy of Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their molecular and pharmacological complexity makes them potentially immunogenic and capable of inducing the development of anti-drug antibodies. TNF inhibitors appear to be the main contributors to immunogenicity because they are widely used, especially in rheumatoid arthritis. Immunogenicity response on these treatments is crucial since the appearance of ADAs has consequences in terms of safety and efficacy. Therefore, this review proposes an overview of the immunogenicity of biological agents used in autoimmune rheumatic diseases highlighting the prevalence of anti-drug antibodies.

Effects of Etanercept on TNF-α Inhibition in Rats with Adenine-Induced Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) constitutes a chronic inflammatory state associated with an increase in inflammatory mediators and profibrotic molecules such as tumor necrosis factor-α (TNF-α). Etanercept (ETA) is a TNF inhibitor widely used in treatment of autoimmune inflammatory diseases. However, the effects of TNF-α inhibition in the establishment of CKD have not been fully elucidated. We evaluate the effects of TNF inhibition by ETA in adenine- (Ad-) induced CKD in rats. Methods: Rats were divided into three groups: control, renal injury model, and model plus ETA (2 mg/kg, 3 times per week (w); sc). Renal injury was induced by Ad administration (100 mg/kg, daily for 2 or 4 w; orogastric). Serum TNF-α levels and biochemical parameters for renal function were evaluated. Histopathological changes in the kidney were assessed using H&E and Masson's trichrome staining and also immunostaining for tubular cells. Results: Ad administration produced a renal functional decline, tubular atrophy, interstitial inflammation, and fibrosis for 2 w, followed by renal anemia, several renal dysfunctions, tubular atrophy, and fibrosis at 4 w. A significant increase in serum TNF-α levels was observed from 2 w of Ad administration and remained elevated up to 4 w. Treatment with ETA partially reduced kidney damage but was very effective to blocking serum TNF-α. Conclusion: Although inhibition of TNF by ETA was very effective in reducing serum TNF-α, this strategy was partially effective in preventing Ad-induced CKD.

Genomic Characterization of SARS-CoV-2 Isolated from Patients with Distinct Disease Outcomes in Mexico.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has shown a wide spectrum of clinical manifestations ranging from asymptomatic infections to severe disease and death. Pre-existing medical conditions and age have been mainly linked to the development of severe disease; however, the potential association of viral genetic characteristics with different clinical conditions remains unclear. SARS-CoV-2 variants with increased transmissibility were detected early in the pandemics, and several variants with potential relevance for public health are currently circulating around the world. In this study, we characterized 57 complete SARS-CoV-2 genomes during the exponential growth phase of the early epidemiological curve in Mexico, in April 2020. Patients were categorized under distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors, the patients were less than 60 years old and with no diagnosed comorbidities A trait-association phylogenomic approach was used to explore genotype-phenotype associations, represented by the co-occurrence of mutations, disease severity outcome categories, and clusters of Mexican sequences. Phylogenetic results revealed a higher genomic diversity compared to the initial viruses detected during the early stage of the local epidemic. We identified a total of 90 single nucleotide variants compared to the Wuhan-Hu-1 genome, including 54 nonsynonymous mutations. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors. IMPORTANCE The genetic association of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with different clinical conditions remains unclear and needs further investigation. In this study, we characterized 57 complete SARS-CoV-2 genomes from patients in Mexico with distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors the patients were less than 60 years old and with no diagnosed comorbidities. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors.

Draft genome sequence of first Vibrio diabolicus in Mexico strain InDRE-D1-M1, an emergent threat.

INTRODUCTION: The complete genome of the marine environmental bacterium Vibrio diabolicus isolated from raw shrimp in the city of Guadalajara in the state of Jalisco in Mexico is reported here. METHODOLOGY: Vibrio spp. it was isolated and identified using standard microbiological and molecular techniques. Whole genome sequencing was performed using the Miseq system (Illumina, USA). RESULTS: The Multi Locus Sequence Typing profile of the isolated Vibrio bacteria coincided only with 4 specific loci (atpA, gyrB, pyrH and recA) and with a total coverage of the species belonging to Vibrio spp. Analysis of the complete genome of the Vibrio isolate and other closely related species, using the genomic fingerprints of the Virtual Analysis Method for PHylogenomic fingerprint estimation (VAMPHyRe) software, revealed the clustering of this species among the clade Vibrio diabolicus. The antibiogram revealed that this strain of Vibrio diabolicus is resistant to ampicillin, which is consistent with the bioinformatic finding of the ß-lactamase enzyme that hydrolyzes carbenicillin class A. CONCLUSIONS: This study demonstrated that the environmental marine bacterium Vibrio diabolicus contains carrier genes associated with pathogenicity and ecological function, which could represent a threat to public health.

Genetic Analysis of SARS-CoV-2 Variants in Mexico during the First Year of the COVID-19 Pandemic.

During the first year of the SARS-CoV-2 pandemic in Mexico, more than two million people were infected. In this study, we analyzed full genome sequences from 27 February 2020 to 28 February 2021 to characterize the geographical and temporal distribution of SARS-CoV-2 lineages and identify the most common circulating lineages during this period. We defined six different geographical regions with particular dynamics of lineage circulation. The Northeast and Northwest regions were the ones that exhibited the highest lineage diversity, while the Central south and South/Southeast regions presented less diversity with predominance of a certain lineage. Additionally, by late February 2021, lineage B.1.1.519 represented more than 89% of all circulating lineages in the country.

Adenosine administration accelerates progression of the cell cycle during rat liver regeneration induced by one-third hepatectomy.

We have shown that adenosine administration is capable of reversing fibrosis in the carbon tetrachloride-induced rat cirrhotic liver, stimulating the diminished proliferative potential of the cirrhotic liver. To characterize adenosine actions on liver cellular proliferation, we used rats subjected to one-third partial hepatectomy (PH). In PH animals acutely administered with adenosine (25-200 mg/kg b.w.), parameters indicative of cell proliferation were determined. In addition, hepatocyte growth factor (HGF), epidermal growth factor, and transforming growth factor-alpha, cyclins, members of the E2F family, proto-oncogenes, and adenosine-receptors were determined through Western blot analyses. Adenosine (100 mg/kg body weight) induced an earlier increase in liver cell proliferation as evidenced by enhanced levels of proliferating cell nuclear antigen, nuclear Ki-67 antigen, and those for cyclins (D1, E, A, and B1), as well as by an increased mitotic index. These effects were also accompanied for a long-lasting increase of serum and liver levels of HGF and liver expression of c-Met and HGF liver activator. Adenosine effects on cell proliferation could be mediated by an early increase in E2F-1 and by that of c-Myc, despite the fact that phosphorylation of the Rb protein and expression of E2F-3 were decreased. Moreover, the liver amount of specific receptors for adenosine was not significantly changed by PH and/or adenosine treatment. In conclusion, these data suggest that adenosine actions can accelerate and increase proliferation in a "primed" liver, mainly through enhancing c-Myc, E2F family, cell-cycle cyclins, and HGF expression. Therefore, these pharmacological adenosine effects suggest a modulating role for the nucleoside on mitogenic events once the liver has been triggered to proliferate.

Surveillance for the identification of cases of acute respiratory infection by enterovirus D68 in children in a tertiary level care hospital during 2014-2016. / Vigilancia epidemiológica para la identificación de casos de infección respiratoria aguda por enterovirus D68 en niños en un hospital de tercer nivel de atención durante 2014-2016

Background: The reemergence of enterovirus D68 (EV-D68) infections in the United States was reported from August-October 2014 (691 cases). In Mexico, an outbreak at the National Institute of Respiratory Diseases was reported (24 cases). The results of epidemiological surveillance of Enterovirus sp. (EV) and other respiratory viruses in a national pediatric tertiary care level hospital are presented. Methods: Following the alert issued by the reemergence of EV-D68 in 2014, epidemiological surveillance -which only detected respiratory viruses by PCR in patients with influenza-like illness using nasopharyngeal swabs- expanded to include children with asthma exacerbation or acute respiratory distress. Positive samples to EV were confirmed and typed by sequencing. Subsequent sequencing was used to obtain the complete viral genome. Results: Of 1705 samples, 13 were positive to EV. Patients with EV presented the following comorbidities: chronic lung disease (7.7%), neoplastic disease (15.4%), allergic asthma/rhinitis (23%), recurrent pneumonia (23%), and other (23%). Of the 13 samples positive for EV, three were positive for EV-D68. These cases required invasive mechanical ventilation, presented no neurological involvement and survived. Conclusions: The impact of the population studied by EV-D68 was lower than that reported in Mexico during the same period. Cases of EV-D68 infection had multiple comorbidities, but few pulmonary comorbidities, which could explain the low attack rate. The epidemiological surveillance and infection prevention system may have contained the outbreak.

Introducción: La reemergencia de las infecciones por Enterovirus D68 (EV-D68) se reportó en los EE.UU. desde agosto-octubre de 2014 (691 casos). En México, un brote se reportó en el Instituto Nacional de Enfermedades Respiratorias (24 casos). Se presentan los resultados de la vigilancia epidemiológica en un hospital pediátrico nacional de tercer nivel para Enterovirus sp. (EV) y otros virus respiratorios. Método: Tras la alerta emitida por la reemergencia del EV-D68 en 2014, la vigilancia epidemiológica ­que solo detectaba virus respiratorios mediante PCR en pacientes con enfermedad tipo influenza mediante toma de hisopados nasofaríngeos­ se expandió para incluir niños con exacerbación de asma o dificultad respiratoria aguda. Las muestras positivas para EV fueron confirmadas y tipificadas por secuenciación. Posteriormente, se utilizó secuenciación de siguiente generación para obtener el genoma viral completo. Resultados: De 1705 muestras, 13 fueron positivas para EV. Los pacientes con EV presentaron la siguiente comorbilidad: enfermedad pulmonar crónica (7.7%), enfermedad neoplásica (15.4%), asma/rinitis alérgica (23%), neumonías de repetición (23%), y otras (23%). De las 13 muestras positivas para EV, tres resultaron positivas para EV-D68. Dichos casos requirieron ventilación mecánica invasiva, no tuvieron afectación neurológica y sobrevivieron. Conclusiones: La afectación por EV-D68 de la población estudiada fue menor que lo reportado en México durante el mismo periodo. Los casos de infección por EV-D68 presentan diversa comorbilidad, aunque escasas enfermedades pulmonares, lo cual pudiera explicar la baja tasa de ataque. La presencia del sistema de vigilancia epidemiológica establecido y la prevención de infecciones pudieron haber contenido el brote.

Genome Sequence of a Rabies Virus Isolated from a Dog in Chiapas, Mexico, 2013.

Rabies virus (RABV), a member of the genus Lyssavirus, causes encephalitis that is almost always fatal following the onset of clinical signs. Here, we report the complete codifying sequence of an RABV isolated from a dog in Mexico. Molecular data showed that this strain belongs to the Chiapas lineage.

Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and apoptosis.

We have characterized an experimental model of ethanol-induced chronic gastritis in which a compensatory mucosal cell proliferation is apparently regulated by lipoperoxidative events. Therefore, the present study is an attempt to further assess the participation of oxidant stress during gastric mucosa proliferation, by administering alpha-tocopherol (vitamin E) to rats with gastritis. A morphometric analysis was done, and parameters indicative of oxidant stress, cellular proliferation (including cyclin D1 levels), apoptotic events, and activities of endogenous antioxidant systems were measured in gastric mucosa from our experimental groups. After ethanol withdrawal, restitution of surface epithelium coincided with increased lipid peroxidation and cell proliferation and further active apoptosis. High alpha-tocopherol dosing (100 IU/kg bw) showed a clear antioxidant effect, abolished cell proliferation, and promoted an early and progressive apoptosis, despite vitamin E also enhancing levels of endogenous antioxidants. Indicators of cell proliferation inversely correlated with apoptotic events, and this relationship was blunted by administering vitamin E, probably by affecting translocation of active cyclin D1 into the nucleus. In conclusion, alpha-tocopherol administration inhibited cell proliferation, leading to a predominance of apoptotic events in ethanol-induced gastric damage. Therefore, the timing and magnitude of lipoperoxidative events seemed to synchronize in vivo cell proliferative and apoptotic events, probably by changing the cell redox state.

Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma.

BACKGROUND: Gastric cancer is one of the main causes of global mortality. Here, reactive oxygen species (ROS) could largely contribute to gastric carcinogenesis. Hence, the present work was aimed to assess the role of ROS, oxidant status, NADPH oxidases (NOXs) expression, during human gastric adenocarcinoma. METHODS: We obtained subcellular fraction from samples of gastric mucosa taken from control subjects (n = 20), and from 40 patients with gastric adenocarcinoma, as well as samples of distant areas (tumour-free gastric mucosa). RESULTS: Parameters indicative of lipid peroxidation and cell proliferation were selectively increased in both tumour-free and in cancerous gastric mucosa, despite of glutathione (GSH) content, glutathione reductase (GR) and superoxide dismutase (SOD) activities were increased in the adenocarcinoma. These high levels of antioxidant defences inversely correlated with down-regulated expression for NOX2 and 4; however, over-expression of NOX1 occurred with increased caspase-3 activity and overexpressed checkpoint 1 (MDC1) and cyclin D1 proteins. In the tumour-free mucosa an oxidant stress took place, without changing total GSH but with decreased activities for GR and mitochondrial SOD; moreover, over-expression of checkpoint 1 (MDC1) correlated with lower NOX2 and 4 expression in this mucosa. CONCLUSIONS: Chronically injured gastric mucosa increases lipoperoxidative events and cell proliferation. In the adenocarcinoma, cell proliferation was further enhanced, oxidant stress decreased which seemed to be linked to NOX1, MDC1 and cyclin D1 over-expression, but with a lower NOXs activity leading a 'low tone' of ROS formation. Therefore, our results could be useful for early detection and treatment of gastric adenocarcinoma.

Complete Genome Sequence of Zika Virus Isolated in Mexico, 2016.

Zika virus belongs to the genus Flavivirus, and its spread remains an international public health emergency. In this report, we describe the obtainment and molecular characterization of a complete viral genome through the direct metagenomic analysis from saliva from an autochthonous transmission case in Mexico.

Hibiscus sabdariffa L. aqueous extract attenuates hepatic steatosis through down-regulation of PPAR-γ and SREBP-1c in diet-induced obese mice.

The growing incidence of obesity is a worldwide public health problem leading to a risk factor for non-alcoholic fatty liver disease, which extends from steatosis to steatohepatitis and cirrhosis. We investigated whether the aqueous extract of Hibiscus sabdariffa L. (Hs) reduces body weight gain and protects the liver by improving lipid metabolism in high fat diet-induced obese C57BL/6NHsd mice. We found that oral administration of the Hs extract reduced fat tissue accumulation, diminished body weight gain and normalized the glycemic index as well as reduced dyslipidemia compared to the obese mice group that did not receive Hs treatment. In addition, Hs treatment attenuated liver steatosis, down-regulated SREBP-1c and PPAR-γ, blocked the increase of IL-1, TNF-α mRNA and lipoperoxidation and increased catalase mRNA. Our results suggest that the anti-obesity, anti-lipidemic and hepatoprotective effects of the Hs extract are related to the regulation of PPAR-γ and SREBP-1c in the liver.