Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses.

This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.

Antiviral resistance in influenza viruses.

Influenza represents a major threat to public health worldwide, vaccination is the most effective strategy to reduce infections. However, achieving adequate vaccination rates is challenging and vaccination does not always guarantee complete protection. For this reason, antiviral drugs represent an important measure to reduce the risk of complications in high-risk patients. However, influenza viruses have a high mutation rate which causes genetic, biochemical, and pathogenic changes that represent a challenge both for the constant replacement of vaccines and reduce their susceptibility to antiviral action. This makes it necessary to determine the mechanisms of these processes, as well as their epidemiological surveillance and, of course, the development of new therapeutic options that may be available in the event of a widespread resistance phenomenon. In this article we review some of the relevant aspects of the replicative cycle of influenza viruses, the antivirals currently used, as well as their resistance mechanisms.

Age and Comorbidities as Risk Factors for Severe COVID-19 in Mexico, before, during and after Massive Vaccination.

During 2020-2023, Mexico had a large COVID-19 emergency with >331,000 adult deaths and one of the highest excess mortalities worldwide. Age at COVID-19 death has been lower in Mexico than in high-income countries, presumably because of the young demographics and high prevalence of chronic metabolic diseases in young and middle-aged adults. SARS-CoV-2 vaccination covered 85% of adults with at least one dose and 50% with booster(s) up to April 2022. No new vaccination efforts or updated boosters were introduced until October 2023; thus, we explored the public health impact of massive SARS-CoV-2 vaccination against ancestral strains and asked whether their real-world protection has persisted through time. We compared three periods with respect to vaccine roll-outs: before, during and after vaccine introduction in a national retrospective cohort of >7.5 million COVID-19 cases. The main findings were that after vaccination, COVID-19 mortality decreased, age at COVID-19 death increased by 5-10 years, both in populations with and without comorbidities; obesity stopped being a significant risk factor for COVID-19 death and protection against severe disease persisted for a year after boosters, including at ages 60-79 and 80+. Middle-aged adults had the highest protection from vaccines/hybrid immunity and they more than halved their proportions in COVID-19 deaths.

Donated Blood Screening for HIV, HCV and HBV by ID-NAT and the Residual Risk of Iatrogenic Transmission in a Tertiary Care Hospital Blood Bank in Puebla, Mexico.

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.

Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

Serum Levels of Galectin-9 are Increased in Cervical Cancer Patients and are Higher in Advanced Clinical Stages.

Purpose: Cervical cancer (CC) is the second most frequent cancer in undeveloped countries. Serum biomarkers could be useful for evaluation of the treatment response and as a complementary means to improve diagnosis. The expression of galectin-9 is altered in cancer tissue, and higher concentrations are found in the serum of cancer patients. The objectives of this study were (a) to determine the serum galectin-9 concentration in patients with intraepithelial lesions and CC, (b) to determine if the concentration was related to the clinicopathological characteristics and (c) to determine if the galectin-9 concentration was related to its expression level in tumour tissue. Patients and Methods: In all, 222 serum samples from women with different diagnoses, including premalignant lesions and CC, as well as samples from women with normal cytology were included in the study. The serum galectin-9 concentration was determined by ELISA. To evaluate the expression level of galectin-9 in CC tissue, immunohistochemistry was performed in 34 CC biopsy specimens. Results: The galectin-9 concentration in the serum of CC patients (8.171 ng/mL) was increased compared with serum from women with normal epithelia (4.654 ng/mL) and those with low-grade (4.806 ng/mL) and high-grade (5.354 ng/mL) intraepithelial lesions (p value < 0.0001). The area under the ROC curve considering the CC group and the control group was 0.882. The optimal cut-off value was ≥6.88 ng/mL, the specificity obtained was 100%, and the sensitivity was 68.2%. In the CC group, the analysis of the clinical stage showed an increase of galectin-9 in the advanced stage IV group. Serum galectin-9 was not related to the level of galectin-9 expression in tissue, which suggests that galectin-9 is not secreted by tumour cells. Conclusion: The serum galectin-9 concentration is related to cancer progression, as the level of this protein is higher in patients with advanced-stage disease.

Decrease in COVID-19 adverse outcomes in adults during the Delta and Omicron SARS-CoV-2 waves, after vaccination in Mexico.

Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46-55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74-85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85-90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1-4 years old.

In silico testing of flavonoids as potential inhibitors of protease and helicase domains of dengue and Zika viruses.

Background: Dengue and Zika are two major vector-borne diseases. Dengue causes up to 25,000 deaths and nearly a 100 million cases worldwide per year, while the incidence of Zika has increased in recent years. Although Zika has been associated to fetal microcephaly and Guillain-Barré syndrome both it and dengue have common clinical symptoms such as severe headache, retroocular pain, muscle and join pain, nausea, vomiting, and rash. Currently, vaccines have been designed and antivirals have been identified for these diseases but there still need for more options for treatment. Our group previously obtained some fractions from medicinal plants that blocked dengue virus (DENV) infection in vitro. In the present work, we explored the possible targets by molecular docking a group of molecules contained in the plant fractions against DENV and Zika virus (ZIKV) NS3-helicase (NS3-hel) and NS3-protease (NS3-pro) structures. Finally, the best ligands were evaluated by molecular dynamic simulations. Methods: To establish if these molecules could act as wide spectrum inhibitors, we used structures from four DENV serotypes and from ZIKV. ADFR 1.2 rc1 software was used for docking analysis; subsequently molecular dynamics analysis was carried out using AMBER20. Results: Docking suggested that 3,5-dicaffeoylquinic acid (DCA01), quercetin 3-rutinoside (QNR05) and quercetin 3,7-diglucoside (QND10) can tightly bind to both NS3-hel and NS3-pro. However, after a molecular dynamics analysis, tight binding was not maintained for NS3-hel. In contrast, NS3-pro from two dengue serotypes, DENV3 and DENV4, retained both QNR05 and QND10 which converged near the catalytic site. After the molecular dynamics analysis, both ligands presented a stable trajectory over time, in contrast to DCA01. These findings allowed us to work on the design of a molecule called MOD10, using the QND10 skeleton to improve the interaction in the active site of the NS3-pro domain, which was verified through molecular dynamics simulation, turning out to be better than QNR05 and QND10, both in interaction and in the trajectory. Discussion: Our results suggests that NS3-hel RNA empty binding site is not a good target for drug design as the binding site located through docking is too big. However, our results indicate that QNR05 and QND10 could block NS3-pro activity in DENV and ZIKV. In the interaction with these molecules, the sub-pocket-2 remained unoccupied in NS3-pro, leaving opportunity for improvement and drug design using the quercetin scaffold. The analysis of the NS3-pro in complex with MOD10 show a molecule that exerts contact with sub-pockets S1, S1', S2 and S3, increasing its affinity and apparent stability on NS3-pro.

Neuropathological Aspects of SARS-CoV-2 Infection: Significance for Both Alzheimer's and Parkinson's Disease.

Evidence suggests that SARS-CoV-2 entry into the central nervous system can result in neurological and/or neurodegenerative diseases. In this review, routes of SARS-Cov-2 entry into the brain via neuroinvasive pathways such as transcribrial, ocular surface or hematogenous system are discussed. It is argued that SARS-Cov-2-induced cytokine storm, neuroinflammation and oxidative stress increase the risk of developing neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Further studies on the effects of SARS-CoV-2 and its variants on protein aggregation, glia or microglia activation, and blood-brain barrier are warranted.

Predicted 3D model of the M protein of Porcine Epidemic Diarrhea Virus and analysis of its immunogenic potential.

The membrane protein M of the Porcine Epidemic Diarrhea Virus (PEDV) is the most abundant component of the viral envelope. The M protein plays a central role in the morphogenesis and assembly of the virus through protein interactions of the M-M, M-Spike (S) and M-nucleocapsid (N) type. The M protein is known to induce protective antibodies in pigs and to participate in the antagonistic response of the cellular antiviral system coordinated by the type I and type III interferon pathways. The 3D structure of the PEDV M protein is still unknown. The present work exposes a predicted 3D model of the M protein generated using the Robetta protocol. The M protein model is organized into a transmembrane and a globular region. The obtained 3D model of the PEDV M protein was compared with 3D models of the SARS-CoV-2 M protein created using neural networks and with initial machine learning-based models created using trRosetta. The 3D model of the present study predicted four linear B-cell epitopes (RSVNASSGTG and KHGDYSAVSNPSALT peptides are noteworthy), six discontinuous B-cell epitopes, forty weak binding and fourteen strong binding T-cell epitopes in the CV777 M protein. A high degree of conservation of the epitopes predicted in the PEDV M protein was observed among different PEDV strains isolated in different countries. The data suggest that the M protein could be a potential candidate for the development of new treatments or strategies that activate protective cellular mechanisms against viral diseases.

Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy.

BACKGROUND: Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy. METHODS: A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. RESULTS: SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. CONCLUSIONS: DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-ß, IL-28A, IL-4, IL-5, IL-13, IL-1ß, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-ß1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.

[Study of confirmed cases of human brucellosis in Puebla, Mexico]. / Estudio de casos confirmados de brucelosis humana en Puebla, México.

BACKGROUND: Human brucellosis is a global health problem. Mexico is one of the main countries affected; timely diagnosis and serological tests are the basis for detection. AIM: To know the frequency of confirmed cases of brucellosis in different of Family Medicine Units of the Mexican Social Security Institute in the state of Puebla, Mexico. METHODS: Cross-sectional study in patients of both genders, adults and pediatrics, with clinical manifestations suggestive of brucellosis; serological tests were performed for the confirmatory diagnosis. RESULTS: Out of a total of 77 patients, 39 (50.6%) were positive, 21 (27.3%) cases coming out of infection, 9 (11.7%) were negative and 8 (10.4%) were defined with immunological memory; of positive cases, 32 (82.1%) were found in the adult group and 30 (76.9%) were female. CONCLUSION: Around half of samples were confirmed as brucellosis, the clinical manifestations of the patients studied were non-specific, which highlights the importance of laboratory diagnosis.

SARS-CoV-2: basic concepts, origin and treatment advances.

The first cases of COVID-19, caused by the virus called SARS-CoV-2, were recorded in Wuhan, China, in December 2019; however, its transmission ability caused for the infection to be practically present throughout the world six months later. The origin of the virus appears to be zoonotic; it has been proposed that it comes from a bat and that it may have had an intermediate host that led to its introduction in the human population. SARS-CoV-2 is an enveloped virus, with a positive single-stranded RNA genome, and it binds to the angiotensin-converting enzyme, present in susceptible cells, to infect the human respiratory system. Although other coronaviruses have been previously known, they have not had the same impact, and, therefore, research on pharmacological treatments is not sufficiently developed to face the current challenge. Almost since the beginning of the epidemic, several molecules have been proposed for the treatment of infection; however, there is not yet a drug available with sufficient effectiveness for treatment. This review describes SARS-CoV-2 main characteristics, its replicative cycle, its possible origin and some advances in the development of antiviral treatments.

Los primeros casos de COVID-19, causada por el virus denominado SARS-CoV-2, se registraron en Wuhan, China, en diciembre de 2019; sin embargo, su capacidad de transmisión ocasionó que seis meses después la infección prácticamente estuviera presente en todo el mundo. El origen del virus parece ser zoonótico; se propone que proviene del murciélago y podría haber tenido un hospedero intermediario que llevó a su introducción en la población humana. SARS-CoV-2 es un virus envuelto, con genoma de ARN de cadena sencilla en sentido positivo y se ancla a la enzima convertidora de angiotensina, presente en las células susceptibles para infectar el sistema respiratorio de los humanos. Aunque previamente se han conocido otros coronavirus, no han tenido el mismo impacto, por lo que la investigación en tratamientos farmacológicos no tiene el desarrollo suficiente para afrontar el reto actual. Casi desde el comienzo de la epidemia se han propuesto moléculas para el tratamiento de la infección, sin embargo, aún no se cuenta con un fármaco con suficiente efectividad terapéutica. En esta revisión se describen las características principales de SARS-CoV-2, su ciclo replicativo, su posible origen y algunos avances en el desarrollo de tratamientos antivirales.

Estudio de casos confirmados de brucelosis humana en Puebla, México / Study of confirmed cases of human brucellosis in Puebla, Mexico

INTRODUCCIÓN: La brucelosis humana es un problema zoo-sanitario global. México es uno de los principales países que se ven afectados, el diagnóstico oportuno y las pruebas serológicas confirmatorias son la base para la detección. OBJETIVO: Conocer la frecuencia de casos confirmados de brucelosis en diferentes Unidades de Medicina Familiar del Instituto Mexicano del Seguro Social en el estado de Puebla, México. PACIENTES Y MÉTODOS: Estudio transversal en pacientes de ambos sexos, adultos y pediátricos, con manifestaciones clínicas sugestivas de brucelosis; se realizaron pruebas serológicas para el diagnóstico confirmatorio. RESULTADOS: De un total de 77 pacientes, se obtuvieron 39 (50,6%) casos positivos, 21 (27,3%) casos saliendo de la infección, 9 (11,7%) negativos y 8 (10,4%) con memoria inmunológica; de los casos positivos, 32 (82,1%) eran adultos y 30 (76,9%) fueron del género femenino. CONCLUSIÓN: Del total de muestras, la mitad tuvo diagnóstico de brucelosis, las manifestaciones clínicas de los pacientes estudiados fueron inespecíficas, lo cual resalta la importancia del diagnóstico de laboratorio.

BACKGROUND: Human brucellosis is a global health problem. Mexico is one of the main countries affected; timely diagnosis and serological tests are the basis for detection. AIM: To know the frequency of confirmed cases of brucellosis in different of Family Medicine Units of the Mexican Social Security Institute in the state of Puebla, Mexico. METHODS: Cross-sectional study in patients of both genders, adults and pediatrics, with clinical manifestations suggestive of brucellosis; serological tests were performed for the confirmatory diagnosis. RESULTS: Out of a total of 77 patients, 39 (50.6%) were positive, 21 (27.3%) cases coming out of infection, 9 (11.7%) were negative and 8 (10.4%) were defined with immunological memory; of positive cases, 32 (82.1%) were found in the adult group and 30 (76.9%) were female. CONCLUSION: Around half of samples were confirmed as brucellosis, the clinical manifestations of the patients studied were non-specific, which highlights the importance of laboratory diagnosis.

SARS-CoV-2: generalidades, origen y avances en el tratamiento / SARS-CoV-2: basic concepts, origin and treatment advances

Resumen Los primeros casos de COVID-19, causada por el virus denominado SARS-CoV-2, se registraron en Wuhan, China, en diciembre de 2019; sin embargo, su capacidad de transmisión ocasionó que seis meses después la infección prácticamente estuviera presente en todo el mundo. El origen del virus parece ser zoonótico; se propone que proviene del murciélago y podría haber tenido un hospedero intermediario que llevó a su introducción en la población humana. SARS-CoV-2 es un virus envuelto, con genoma de ARN de cadena sencilla en sentido positivo y se ancla a la enzima convertidora de angiotensina, presente en las células susceptibles para infectar el sistema respiratorio de los humanos. Aunque previamente se han conocido otros coronavirus, no han tenido el mismo impacto, por lo que la investigación en tratamientos farmacológicos no tiene el desarrollo suficiente para afrontar el reto actual. Casi desde el comienzo de la epidemia se han propuesto moléculas para el tratamiento de la infección, sin embargo, aún no se cuenta con un fármaco con suficiente efectividad terapéutica. En esta revisión se describen las características principales de SARS-CoV-2, su ciclo replicativo, su posible origen y algunos avances en el desarrollo de tratamientos antivirales.

Abstract The first cases of COVID-19, caused by the virus called SARS-CoV-2, were recorded in Wuhan, China, in December 2019; however, its transmission ability caused for the infection to be practically present throughout the world six months later. The origin of the virus appears to be zoonotic; it has been proposed that it comes from a bat and that it may have had an intermediate host that led to its introduction in the human population. SARS-CoV-2 is an enveloped virus, with a positive single-stranded RNA genome, and it binds to the angiotensin-converting enzyme, present in susceptible cells, to infect the human respiratory system. Although other coronaviruses have been previously known, they have not had the same impact, and, therefore, research on pharmacological treatments is not sufficiently developed to face the current challenge. Almost since the beginning of the epidemic, several molecules have been proposed for the treatment of infection; however, there is not yet a drug available with sufficient effectiveness for treatment. This review describes SARS-CoV-2 main characteristics, its replicative cycle, its possible origin and some advances in the development of antiviral treatments.

A comprehensive update of the status of hepatitis C virus (HCV) infection in Mexico-A systematic review and meta-analysis (2008-2019).

INTRODUCTION AND OBJECTIVES: HCV infection is targeted by the WHO's Global Health Sector Strategy on Viral Hepatitis to be reduced notably by 2030. However, renovated epidemiological data is needed to line up with such goals. Herein, we provide an updated review of incidence, prevalence, genotypes (GTs), and risk factors (RFs) of HCV infection in Mexico to build elimination strategies. MATERIAL AND METHODS: HCV incidence was charted using the cumulative new cases/year at week 52. Prevalence, GTs, and RFs data from low-risk (LR-G) and high-risk (HR-Gs) groups were searched in PubMed/MEDLINE/Medigraphic/Scielo databases from January 2008 to December 2019 as per PRISMA guidelines. Weighted mean prevalence (WMP) was estimated; GTs and RFs were registered. RESULTS: In this study, 25,247 new cases were reported. Ten states accumulated 76.32% of HCV incidence that peaked in men at 50-59 years and women at 60-64 years. Thirty-four studies revealed a WMP between 0.774%-2.5% in LR-Gs and 11.8%-39.6% in HR-Gs that included mainly prison inmates, drug users, and dialyzed patients. GT1 and GT2 were predominant; GT3a emerged. Subtypes 1a and 1b circulate differentially, whereas novel GT2 subtypes appeared. Unsafe blood transfusion was infrequent in younger groups, but parenteral/intravenous transmission through drug-related risk behaviors has arisen. CONCLUSIONS: HCV transmission increased notably among LR-Gs and HR-Gs in Mexico. Novel genotypes/subtypes emerged as well as risky behavioral routes of transmission. A national elimination strategy will require pro-active screening in designated risk groups, research in molecular epidemiology, medical training, robust epidemiological databases, and antiviral treatment available to all eligible HCV-infected patients.

Glycogene expression profiles from a HaCaT cell line stably transfected with HPV16 E5 oncogene.

The altered expression of glycan antigens has been reported during cervix transformation, demonstrating increased mRNA levels of certain glycogenes. Human papillomavirus (HPV) is the aetiological agent of cervical cancer. High risk HPV E5 is considered an oncogene and has been implicated in cell transformation. E6 and E7 HPV oncoproteins modify the expression of certain glycogenes. The role of the E5 HPV protein in glycogene expression changes has not yet been reported. The aim of the present study was to determine the effects of HPV16 E5 oncoprotein on glycogene expression. For these, a microarray assay was performed using the HaCaT cell line and altered glycogenes were identified. The mRNA levels of certain glycogenes were determined via reverse transcription­quantitative PCR (RT­qPCR). Using in silico analysis, the present study identified that glycosylation pathways were altered by E5. Microarray analysis revealed alterations in certain glycogenes, including the upregulation of ST6GAL1, ST3GAL3, CHST2 and MANBA, and the downregulation of UGT2B15, GALNT11, NDST2 and UGT1A10. Increased mRNA levels were confirmed via RT­qPCR for sialyltransferases genes. Additionally, in silico analysis was performed to identify glycosylation networks altered in the presence of the E5 oncoprotein. The analysis revealed that E5 could modify glycan sialylation, the N­glycosylation pathway, keratan sulfate and glycosaminoglycan synthesis. To the best of our knowledge, the current study was the first to determine the role of the HPV16 E5 oncoprotein in glycogene expression changes. The results indicated that increased sialyltransferase mRNA levels reported in pre­malignant and malignant cervical tissues could be the result of E5 oncoprotein expression. The results provide a possible role of HPV infection on glycosylation changes reported during cervix transformation.

Histone H3K9 and H3K14 acetylation at the promoter of the LGALS9 gene is associated with mRNA levels in cervical cancer cells.

Galectin-9 levels have been reported to be altered in several cancer types, but the mechanism that regulates the expression of Galectin-9 has not been clarified. Galectin-9 is encoded by the LGALS9 gene, which gives rise to eight mRNA variants. The aims of this study were: (a) to identify the mRNA variants of LGALS9, (b) to characterize CpG methylation and H3K9 and H3K14 histone acetylation at the promoter of the LGALS9 gene, and (c) to characterize the relationship between these modifications and LGALS9 expression level in cervical cancer cells. All mRNA variants were detected in HaCaT (nontumoural keratinocytes) and SiHa cells, and seven were observed in HeLa cells. The promoter region of LGALS9 contains eight CpG dinucleotides. No hypermethylation pattern related to low LGALS9 expression was identified in tumour cells. Chromatin immunoprecipitation analysis demonstrated higher acetylation of H3K9ac and H3K14ac in HaCaT cells, which was related to higher mRNA levels. The presence of the mRNA variants suggests that alternative splicing may regulate the expression of galectin-9 isoforms. The results of this study suggest that histone acetylation, but not promoter CpG methylation, may be involved in the transcriptional regulation of the LGALS9 gene.