RESUMEN

Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking. Like APOL3-KO, APOL1Δ induces PI4KB dissociation from APOL3, linked to reduction of mitophagy flux and production of mitochondrial reactive oxygen species. APOL1 and APOL3, respectively, can interact with the mitophagy receptor prohibitin-2 and the mitophagosome membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). While APOL1 conditions PI4KB and APOL3 involvement in mitochondrion fission and mitophagy, APOL3-VAMP8 interaction promotes fusion between mitophagosomal and endolysosomal membranes. We propose that APOL3 controls mitochondrial membrane dynamics through interactions with the fission factor PI4KB and the fusion factor VAMP8.

Asunto(s)

Apolipoproteína L1 , Membranas Mitocondriales , Apolipoproteína L1/genética , Membranas Mitocondriales/metabolismo , Aparato de Golgi/metabolismo , Mitocondrias , 1-Fosfatidilinositol 4-Quinasa/metabolismo , Apolipoproteínas/genética , Apolipoproteínas/metabolismo , Dinámicas Mitocondriales

RESUMEN

Multiple sclerosis (MS) is a common neurological disease among young people of working age, which tends to increase the number of cases registered in the world and in the Russian Federation. However, with improved diagnostics and the emergence of new drugs that change the course of MS (disease-modifying therapy), people's life expectancy increases and the percentage of patients in the older age group increases as well. In this article, we consider the possibility of developing MS among people over 50 years of age, features of the course, diagnosis and treatment.

Asunto(s)

Esclerosis Múltiple , Humanos , Persona de Mediana Edad , Anciano , Adolescente , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/terapia , Esperanza de Vida , Federación de Rusia/epidemiología

RESUMEN

SARS-CoV-2 vaccination significantly reduces morbidity and mortality, but has less impact on viral transmission rates, thus aiding viral evolution, and the longevity of vaccine-induced immunity rapidly declines. Immune responses in respiratory tract mucosal tissues are crucial for early control of infection, and can generate long-term antigen-specific protection with prompt recall responses. However, currently approved SARS-CoV-2 vaccines are not amenable to adequate respiratory mucosal delivery, particularly in the upper airways, which could account for the high vaccine breakthrough infection rates and limited duration of vaccine-mediated protection. In view of these drawbacks, we outline a strategy that has the potential to enhance both the efficacy and durability of existing SARS-CoV-2 vaccines, by inducing robust memory responses in the upper respiratory tract (URT) mucosa.

Asunto(s)

COVID-19 , Vacunas Virales , Humanos , Vacunas contra la COVID-19 , Inmunidad Mucosa , COVID-19/prevención & control , SARS-CoV-2 , Infección Irruptiva , Vacunación

RESUMEN

INTRODUCTION: Results from several clinical trials suggest there is a dose-response effect for beta interferon-1a (INFß1a) in multiple sclerosis (MS). METHODS: Our objective was to confirm these results through a retrospective analysis of patients with MS who had breakthrough disease (BD) on intramuscular (IM) INFß1a (Avonex®) once per week (QW), who were switched to twice per week (BIW) IM INFß1a between 1995 and 2015. The primary outcome measure was no further BD for at least 24 months. A secondary outcome measure was decrease in mean percentage of disease activity over time. BD was defined as continued relapses, new T2 or enhanced lesions on magnetic resonance imaging (MRI) of the brain, or worsening of the Expanded Disability Status Scale (EDSS) or the neurological examination. RESULTS: Among 92 patients on QW IM INFß1a, 53 patients with BD were switched to BIW IM INFß1a. Of these 53 patients, 44 had adequate follow-up for at least 2 years. Twenty-three of these had no further BD for 24 months or more (range 24-192 months). Beta interferon neutralizing antibody testing was negative in 19 patients. An intent-to-treat analysis of the uncensored data from 52 switched patients also supported a treatment benefit. CONCLUSION: For patients with MS having breakthrough disease on QW INFß1a, switching to more frequently administered INFß may be an option. Advantages to using IM INFß1a for this include no skin reactions and a lower incidence of neutralizing antibodies. Further pragmatic, observational, larger-group studies comparing treatment with Avonex® and higher dosed IM INFß1a, such as the recently FDA-approved IM peginterferon beta-1a, may be indicated.

RESUMEN

Diabetes mellitus is a metabolic disease that causes hyperglycemia. In COVID-19 patients the severity of the disease depends on myriad factors but diabetes mellitus is the most important comorbidity. The current review was conducted to investigate the virulence of SARS-CoV-2 and disease severity of COVID-19 in type 2 diabetes mellitus patients and relevant treatment. The literature published in PubMed, Scopus, Web of Science, and Google Scholar was reviewed up to September 2021. The keywords including SARS-CoV-2, type 2 diabetes mellitus in COVID-19, hyperglycemia in COVID-19, opportunistic infections in type 2 diabetes mellitus and COVID-19 were used in different combinations. Hyperglycemic individuals over-express ACE-2 receptors in the lungs thus increasing the SARS-CoV-2 susceptibility and replication. Although dipeptidyl peptidase-4 plays an important role in glucose homeostasis, additionally it also stimulates the production of proinflammatory cytokines such as IL-6 and TNF-α creating a cytokine storm. Cytokine storm might be responsible for respiratory insufficiency in severe COVID-19 patients. Type 2 diabetes mellitus is associated with immunosuppression and the patients are prone to get many opportunistic infections. Type 2 diabetes mellitus patients with severe COVID-19 have lymphopenia. Moreover, in type 2 diabetes mellitus patients the neutrophils exhibit decreased chemotaxis, hydrogen peroxide production, and phagocytosis. Reduction in lymphocyte count and defective neutrophil capacity renders them with COVID-19 susceptible to opportunistic bacterial and fungal infections increasing the mortality rate. The opportunistic bacterial infections in COVID-19 patients were due to Staphylococcus aureus, Streptococcus pneumonia, and coagulase-negative Staphylococci, E. coli, Pseudomonas aeruginosa, and Klebsiella sp. In COVID-19 patients with type 2 diabetes mellitus, mucormycosis was found to be the most common fungal infection with a higher predilection to males. Hyperglycemia in COVID-19 patients with type 2 diabetes mellitus enhances the SARS-CoV-2 replication with an adverse outcome. A strong correlation exists between the poor prognosis of COVID-19 and type 2 diabetes mellitus. Proper glycemic control in COVID-19 patients with diabetes mellitus might lessen the severity of the disease.

RESUMEN

Hereditary dilated cardiomyopathy (DCM) is a primary disease of cardiac myocytes caused by mutations in genes encoding proteins with a diverse array of functions. Mutations in the LMNA gene, encoding the nuclear envelope protein lamin A/C, are the second most common causes of DCM. The phenotype is characterized by progressive cardiac dysfunction, leading to refractory heart failure, myocardial fibrosis, cardiac arrhythmias, and sudden cardiac death. The molecular pathogenesis of DCM caused by the LMNA mutations is not well known. The LMNA protein is involved in nuclear membrane stability. It is also a guardian of the genome involved in the processing of the topoisomerases at the transcriptionally active domain and the repair of double-stranded DNA breaks (DSBs). Deletion of the mouse Lmna gene in cardiac myocytes leads to premature death, DCM, myocardial fibrosis, and apoptosis. The phenotype is associated with increased expression of the cytosolic DNA sensor cyclic GMP-AMP synthase (CGAS) and activation of the DNA damage response (DDR) pathway. Genetic blockade of the DDR pathway, upon knockout of the Mb21d1 gene encoding CGAS, prolonged survival, improved cardiac function, partially restored levels of molecular markers of heart failure, and attenuated myocardial apoptosis and fibrosis in the LMNA-deficient mice. The findings indicate that targeting the CGAS/DDR pathway might be beneficial in the treatment of DCM caused by mutations in the LMNA gene.

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-ß 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-ß 1a compared to low dose IFN-ß 1a in severe COVID-19 cases. METHODS: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-ß 1a (Recigen) (Subcutaneous injections of 88 µg (24 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally) and the control group was treated with low-dose IFN-ß 1a (Recigen) (Subcutaneous injections of 44 µg (12 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400 mg/100 mg twice a day for 10 days, orally). RESULT: A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-ß1a was shorter than that for cases treated with high-dose IFN-ß1a (6 vs 10 days; P = 0.018). The mortality rates in intervention and control group were 41% and 36.5%, respectively. CONCLUSION: The use of high-dose IFN-ß 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-ß 1a. TRIAL REGISTRATION: This trial has been registered as ClinicalTrials.gov, NCT04521400.

Asunto(s)

Antivirales/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Interferón beta-1a/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , Femenino , Humanos , Interferón beta-1a/efectos adversos , Masculino , Persona de Mediana Edad , Mortalidad , Resultado del Tratamiento

RESUMEN

OBJECTIVES: We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial. PARTICIPANTS: The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-ß 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences. INTERVENTION AND COMPARATOR: COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-ß 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-ß 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation. MAIN OUTCOMES: Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. SECONDARY OUTCOMES: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. RANDOMIZATION: Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra). TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20th 2020, and the end date was on September 4th 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials ( www.clinicaltrials.gov ; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400 , registered August 18, 2020 and first available online August 20, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Asunto(s)

Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta-1a/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Antivirales/administración & dosificación , COVID-19 , Estudios de Casos y Controles , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Humanos , Interferón beta-1a/administración & dosificación , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Mortalidad/tendencias , Evaluación de Resultado en la Atención de Salud , Pandemias , Alta del Paciente , Neumonía Viral/epidemiología , Neumonía Viral/virología , Respiración Artificial/estadística & datos numéricos , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , SARS-CoV-2

RESUMEN

OBJECTIVES: We will investigate the effectiveness of Interferon Beta 1a, compared to Interferon Beta 1b and the usual therapeutic regimen in COVID-19 in patients that have tested positive and are moderately to severely ill. TRIAL DESIGN: This is a single center, open label, randomized, controlled, parallel group, clinical trial that will be conducted at Loghman Hakim Medical Education Center in conjunction with Shahid Beheshti University of Medical Sciences. PARTICIPANTS: Sixty COVID-19 confirmed cases (using the RT-PCR test) will be enrolled in the trial between April 9th to April 14th 2020. Patients will be randomly assigned to the intervention groups or the control group with the following eligibility criteria: ≥ 18 years of age AND (oxygen saturation (SPO2) ≤ 93% OR respiratory rate ≥ 24) AND at least one of the following: Contactless infrared forehead thermometer temperature of ≥37.8, cough, sputum production, nasal discharge, myalgia, headache or fatigue on admission, and time of onset of the symptoms should be acute (Days ≤ 14). Although Hydroxychloroquine will be administered in a single dose, patients with heart problems (prolonged QT or PR intervals, second- or third-degree heart block, and arrhythmias including torsade de pointes) will be excluded. Other exclusion criteria include using drugs with potential interaction with Hydroxychloroquine + Lopinavir/Ritonavir, Interferon-ß 1a, Interferon-ß 1b, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results and refusal to participate. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences and Health Services. INTERVENTION AND COMPARATOR: COVID-19 confirmed patients will be randomly assigned to one of three groups, with 20 patients in each. The first group (Arm 1) will receive Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1a (Recigen), the second group (Arm 2) will be administered Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra) + Interferon-ß 1b (Ziferon), and the control group (Arm 3) will be treated by Hydroxychloroquine + Lopinavir / Ritonavir (Kaletra). MAIN OUTCOMES: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. Secondary outcomes include mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. If any patient dies, we have reached an important secondary outcome. SpO2 Improvement between the last and first day of hospitalization, using pulse-oximetry. Duration of hospitalization from date of randomization until the date of hospital discharge or date of death from any cause, whichever comes first. Incidence of new mechanical ventilation uses from date of randomization until the last day of the study. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. Statistical analysis will be performed by R version 3.6.1 software. We will use Kaplan-Meier to analyze the time to clinical improvement (compared with a log-rank test). Hazard ratios with 95% confidence intervals will be calculated using the Cox proportional-hazards model in crude and adjusted analysis. RANDOMIZATION: Eligible patients will be randomly assigned in a 1:1:1 ratio to receive either Interferon Beta 1a, Interferon Beta 1b or standard care only. Patients will be randomly allocated to three therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Of the 60 patients who underwent randomization, 20 patients were assigned to receive Interferon beta-1a, 20 patients were assigned to receive Interferon beta 1b plus standard care and the rest of patients were assigned to receive the standard care alone. TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on 9th April 2020 and the end date was on 14th April 2020. Last point of data collection will be the last day on which all of the 60 participants have had an outcome of clinical improvement or death, completing the study's follow-up time window. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov; identification number NCT04343768, registered April 8, 2020 and first available online April 13, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Asunto(s)

Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta-1a/uso terapéutico , Interferon beta-1b/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antivirales/efectos adversos , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Combinación de Medicamentos , Quimioterapia Combinada , Interacciones Huésped-Patógeno , Humanos , Hidroxicloroquina/uso terapéutico , Interferón beta-1a/efectos adversos , Interferon beta-1b/efectos adversos , Irán , Lopinavir/uso terapéutico , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/uso terapéutico , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

We compared the efficacy and safety of a biosimilar form of beta-interferon-1a (Actovex) versus the reference product in the treatment of relapsing remitting multiple sclerosis (RRMS). In a double blind, randomized phase 3 clinical trial, we evaluated 138 patients with RRMS that were allocated to receive the biosimilar medication and the reference treatment (30 µg intramuscular, weekly for one year). We investigated changes in EDSS, relapse rate and MRI changes within one year. In sixty-nine patients who were allocated to each arm and analyzed mean age and its standard deviation was 32.4 ± 8.8 and 31.5 ± 8 for the biosimilar medication and the reference arm respectively. One-year follow-up revealed a mean difference of 0.084 in EDSS (95% CI: 0.069-0.237) between the two groups in favor of the biosimilar medication. This value did not exceed the predefined non-inferiority margin of 0.1. There were no statistically significant differences in relapse rate and systemic and local adverse events of the two groups. The results show that the biosimilar interferon 1-a is non-inferior to the reference product in terms of efficacy while it demonstrates comparable safety. In conclusion the biosimilar interferon 1-a can be considered as an effective and safe alternative to the reference product due to lower cost and more availability.

RESUMEN

BACKGROUND: Seasonal allergic rhinitis (SAR) caused by intermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with profound effects on quality of life, work productivity, and school performance. Although both the genotype and environmental factors can contribute to the immunologic basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear. METHODS: To address these questions, nasal epithelial brushings were collected from 29 patients with SAR and 31 control subjects during and after the pollen season. We then implemented an orbitrap-based, bottom-up, label-free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant (DA) proteins among the 4 sample groups. RESULTS: We identified a total of 133 DA proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, cystatin 1 and myeloblastin, the former of which protects against protease activity of allergens and the latter with a role in epithelial barrier function, were DA in patients with SAR and control subjects, irrespective of season. Moreover, interferon-inducible protein with tetratricopeptide repeats 1, cystatin 1, and interferon-inducible protein with tetratricopeptide repeats 3 were found to be differentially regulated between patients with SAR and control subjects, with inverse abundance dynamics during the transition from fall to spring. CONCLUSION: We identified type 1 interferon-regulated proteins as biomarkers in patients with SAR, potentially playing an important role in its pathogenesis. Moreover, when compared with patients with SAR, healthy subjects exhibit an antagonistic proteomic response across seasons, which might prove to be a therapeutic target for disease prevention.

Asunto(s)

Biomarcadores/metabolismo , Cistatina C/metabolismo , Mucosa Nasal/metabolismo , Rinitis Alérgica Estacional/inmunología , Cistatinas Salivales/metabolismo , Adulto , Alérgenos/inmunología , Cistatina C/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Interferón Tipo I/metabolismo , Masculino , Mieloblastina/genética , Mieloblastina/metabolismo , Mucosa Nasal/patología , Polen/inmunología , Proteoma , Cistatinas Salivales/genética , Estaciones del Año , Transducción de Señal/genética , Adulto Joven

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. METHODS: Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. RESULTS: Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05). CONCLUSION: Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

RESUMEN

In this work, a high-resolution CGE method for quantification and purity determination of recombinant proteins was developed, involving a single-component inclusion bodies (IBs) solubilization solution. Different recombinant proteins expressed as IBs were used to show method capabilities, using recombinant interferon-ß 1b as the model protein for method validation. Method linearity was verified in the range from 0.05 to 0.40 mg/mL and a determination coefficient (r(2) ) of 0.99 was obtained. The LOQs and LODs were 0.018 and 0.006 mg/mL, respectively. RSD for protein content repeatability test was 2.29%. In addition, RSD for protein purity repeatability test was 4.24%. Method accuracy was higher than 90%. Specificity was confirmed, as the method was able to separate recombinant interferon-ß 1b monomer from other aggregates and impurities. Sample content and purity was demonstrated to be stable for up to 48 h. Overall, this method is suitable for the analysis of recombinant proteins in IBs according to the attributes established on the International Conference for Harmonization guidelines.

Asunto(s)

Electroforesis Capilar/métodos , Cuerpos de Inclusión/química , Proteínas Recombinantes/análisis , Humanos , Interferon beta-1b , Interferón beta/química , Modelos Lineales , Modelos Químicos , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Solubilidad

RESUMEN

Objective To explore the essential of cerebroprotein hydrolysate injection in the manage-ment of epidemic encephalitis B.MethodsTwo hundred and thirty-two patients with epidemic ence-phalitis B were randomly divided into two groups,one hundred and twenty-six patients in treating group,and one hundred and six patients in controlled group.Beside the conventional and symptomatic therapy,the patients in treating group received the management of cerebroprotein hydrolysate injection 10 mL+5% glucose solution 250 mL,iv drip,qd for 5 d and those in controlled group received the management of interferon?1b 1 MIU,sc,qd for 5 d.ResultsThe total clinical effective rates in treating group and controlled group were 94.6% and 82.6% respectively,there were remark-ably differences between two groups(P

RESUMEN

0.05)was found in the 2 groups.The costs of the 2 groups were 3270.84 yuan and 10 873.20 yuan respectively,and the cost-effectiveness rates were 37.38 and 117.55 respectively.Conclusion:Scheme A is an effective,safe and economical scheme in the treatment of CHB.

RESUMEN

OBJECTIVE: To observe the inhibiting effect of Interferon-alpha 1b(IFNa-1b) on proliferation of human tenon capsule fibroblasts. METHODS: Human tenon capsule fibroblasts were cultured in vitro and MTT method was used to detect the inhibiting effect of IFNa-1b on human tenon capsule fibroblasts. RESULTS: There was significant difference in OD values between 10~6IU/ml group(0. 1 109?0. 0 585) and control group(0.2535?0. 0502), the inhibition rate in IFN group was 56.25%. CONCLUSION: IFNa-1b has significant effect on inhibiting proliferation of human tenon capsule fibroblasts.

RESUMEN

OBJECTIVE:To prepare recombinant interferon(INF)?1b chitosan plastics and to establish a way for its quality control.METHODS:The plastics was prepared with chitosan as the main excipients,the content of INF?1b was de-termined by di-quinoline methanoic acid kit,the stability of the plastics was determined and its skin irritation test was con-ducted.RESULTS:The linear range for recombinant INF?1b in the prepared paint was1～11mg/L(r=0.9999)with methodological recovery rate at101.04%,RSD=1.05%(n=5).CONCLUSION:The recombinant INF?1b chitosan plastics is simple in preparation,accurate in assaying,stable in quality yet the skin irritation induced by which was failed to be noted.