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BACKGROUND: Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1ß. METHODS: Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals. RESULTS: The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1ß in the cortex and hippocampus of mice brains. CONCLUSIONS: Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation.
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Doenças Neuroinflamatórias , Estresse Oxidativo , Pentilenotetrazol , Convulsões , Animais , Camundongos , Convulsões/metabolismo , Convulsões/induzido quimicamente , Convulsões/patologia , Masculino , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologia , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Doença Crônica , Comportamento AnimalRESUMO
BACKGROUND: Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation. RESULTS: Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05). CONCLUSIONS: Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient's response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.
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Epilepsia , Humanos , Epilepsia/tratamento farmacológico , Epilepsia/genética , Carbamazepina/uso terapêutico , Anticonvulsivantes/uso terapêutico , Alelos , Encéfalo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genéticaRESUMO
A 34-year-old non hypertensive, non-diabetic and ill looking weak woman came to our emergency department with shortness of breath NYHA III-IV, severe bilateral pedal edema extending up to the thighs and gross ascites. Physical examination revealed 3mm pitting ankle and leg edema and hemodynamically was stable with raised jugular venous pressure. There was a closing and opening mechanical click on Cardiac auscultation. At the lower left sternal border, there was grade 2/6 holodiastolic rumble and a grade 2/6 systolic murmur. She had history of mitral valve replacement and tricuspid valve replacement in 2017 with mechanical valves then she had Redo tricuspid valve replacement with mechanical prosthesis again after four months. No known food or drug allergy and psychosocial issues. Her routine bloods Labs were normal and COVID-19 was negative. On chest X-ray P/A view images and echo showed markedly gross left sided pleural effusion. In Coronary angiogram showed normal coronaries and stuck tricuspid valve (Fig.1). Echocardiography report showed preserved LV systolic function (EF=57%), dilated left atrium and right atrium. Prosthetic mitral valve was seen at mitral position, well seated and well-functioning. The mechanical mitral valve was functioning well with normal disc motion with no thrombus formation. Prosthetic tricuspid valve was seen at tricuspid level with peak gradient of 22mmHg and shown stuck mechanical tricuspid discs stuck throughout the cardiac cycle, in a fully open position (Fig.2A and 2B). Atrial fibrillation was shown on ECG. The diagnosis was made as; pannus formation resulting in mechanical TV thrombosis.
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This study aimed to determine the molecular prevalence and associated risk factors of theileriosis in sheep from Balochistan, Pakistan. For this purpose, a total of 408 blood samples were collected from tick-infested sheep in three different zones of Balochistan (i.e., Quetta, Zhob, and Loralai). All the collected samples were analyzed using conventional microscopy techniques, polymerase chain reaction (PCR), 18S small subunit rRNA gene sequencing, and phylogenetic analysis. The results of the microscopy and PCR confirmed the highest prevalence of Theileria species in district Zhob (14.22% and 15.68%) followed by district Loralai (11.52% and 13.97%) and district Quetta (10.29% and 12.00%), respectively. In addition, the prevalence of T. lestoquardi was higher in female sheep (84.12%), followed by adult sheep (74.71%) and the Hernai breed of sheep (28.23%) in the studied area. Similarly, the prevalence of theileriosis was higher in the summer season (40.59%), followed by the spring, autumn, and winter seasons. However, numerous risk factors such as age, sex, area, season, and breeds of the sheep were not significantly correlated (P > 0.05) with the presence of T. lestoquardi, except tick abundance and feeding pattern of animals (P < 0.05). Furthermore, sequencing and phylogenetic analyses of the isolated T. lestoquardi displayed 99% sequence similarity with isolates from Germany, Egypt, Iraq, India, Iran, and Pakistan. Altogether these results showed that T. lestoquardi is the main species causing ovine theileriosis in Balochistan. As a result, large-scale studies are required to design practical control approaches to reduce the risk of theileriosis infection in Balochistan, Pakistan.
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Doenças dos Ovinos , Theileria , Theileriose , Carrapatos , Bovinos , Animais , Ovinos/genética , Feminino , Theileriose/epidemiologia , Paquistão/epidemiologia , Filogenia , Carrapatos/genética , RNA Ribossômico 18S/genética , Fatores de Risco , Doenças dos Ovinos/epidemiologiaRESUMO
Objective: To find out the prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting (CABG). Methods: This retrospective study was conducted in Northwest General Hospital and Research center Hayatabad, Peshawar over a duration of 15 months (December 2020 - March 2022). Every patient was tested through regular laboratory investigations. Diabetes mellitus was established according to WHO standards of fasting plasma glucose >126 mg/dl or two hours postprandial glucose level of 200 mg/dl. Data were analyzed using SPSS. Mean and standard deviation was used for quantitative data. Frequency and percentages were used for qualitative data. Shapiro Wilk's test was done to find the normality of the data. Results: Out of a total of 360 candidates, 129 (36%) individuals were non-diabetic and 231 (64%) candidates were diabetic. Among the diabetic patients, 64 (28%) were female and 167 (72%) were males with a ratio of 1:2.6 respectively. Conclusion: Prevalence of diabetes was 64% among the CABG population. Since the prevalence of diabetes can significantly affect the outcomes of people undergoing CABG, it is essential to generate awareness regarding diabetes among healthcare workers as well as the general population. More extensive research is needed to be carried by various health care centers to figure out the prevalence of diabetes mellitus in cardiac surgery patients.
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This article presents non-invasive sensing-based diagnoses of pneumonia disease, exploiting a deep learning model to make the technique non-invasive coupled with security preservation. Sensing and securing healthcare and medical images such as X-rays that can be used to diagnose viral diseases such as pneumonia is a challenging task for researchers. In the past few years, patients' medical records have been shared using various wireless technologies. The wireless transmitted data are prone to attacks, resulting in the misuse of patients' medical records. Therefore, it is important to secure medical data, which are in the form of images. The proposed work is divided into two sections: in the first section, primary data in the form of images are encrypted using the proposed technique based on chaos and convolution neural network. Furthermore, multiple chaotic maps are incorporated to create a random number generator, and the generated random sequence is used for pixel permutation and substitution. In the second part of the proposed work, a new technique for pneumonia diagnosis using deep learning, in which X-ray images are used as a dataset, is proposed. Several physiological features such as cough, fever, chest pain, flu, low energy, sweating, shaking, chills, shortness of breath, fatigue, loss of appetite, and headache and statistical features such as entropy, correlation, contrast dissimilarity, etc., are extracted from the X-ray images for the pneumonia diagnosis. Moreover, machine learning algorithms such as support vector machines, decision trees, random forests, and naive Bayes are also implemented for the proposed model and compared with the proposed CNN-based model. Furthermore, to improve the CNN-based proposed model, transfer learning and fine tuning are also incorporated. It is found that CNN performs better than other machine learning algorithms as the accuracy of the proposed work when using naive Bayes and CNN is 89% and 97%, respectively, which is also greater than the average accuracy of the existing schemes, which is 90%. Further, K-fold analysis and voting techniques are also incorporated to improve the accuracy of the proposed model. Different metrics such as entropy, correlation, contrast, and energy are used to gauge the performance of the proposed encryption technology, while precision, recall, F1 score, and support are used to evaluate the effectiveness of the proposed machine learning-based model for pneumonia diagnosis. The entropy and correlation of the proposed work are 7.999 and 0.0001, respectively, which reflects that the proposed encryption algorithm offers a higher security of the digital data. Moreover, a detailed comparison with the existing work is also made and reveals that both the proposed models work better than the existing work.
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Aprendizado Profundo , Pneumonia , Algoritmos , Teorema de Bayes , Humanos , Redes Neurais de Computação , Pneumonia/diagnóstico , PrivacidadeRESUMO
Objectives: In this study we determine the modifiable factors related to bleeding and transfusion in post-cardiac surgery patients who underwent open heart surgery. Methods: This is a retrospective study that include two hundred patients who had undergone open heart surgery (OHS) at Northwest General Hospital and Research Center from December 2018 to July 2021. Platelet count and hemoglobin level were measured in the pre-operative period. Results: This study included both male and female patients. Postoperative platelets were counted as follow: 50-100 x109 L in 3.0% cases, 101-150 x109 L seen in 27.5% cases, and >150 x 109 L in 69.5% cases which required transfusion. We have also reported the increased requirement of transfusion of blood and blood products in patients with pre-operative hemoglobin (Hb) < 10 g/dl. Conclusion: Correction of pre-op Hb, post-op platelet count and total bypass time are the significant and preventable parameters in patients undergoing cardiac surgery if proper pre-op assessment of the patient is performed.
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Members of the Pegivirus genus, family Flaviviridae, widely infect humans and other mammals, including nonhuman primates, bats, horses, pigs, and rodents, but are not associated with disease. Here, we report a new, genetically distinct pegivirus in goose (Anser cygnoides), the first identified in a nonmammalian host species. Goose pegivirus (GPgV) can be propagated in goslings, embryonated goose eggs, and primary goose embryo fibroblasts, and is thus the first pegivirus that can be efficiently cultured in vitro Experimental infection of GPgV in goslings via intravenous injection revealed robust replication and high lymphotropism. Analysis of the tissue tropism of GPgV revealed that the spleen and thymus were the organs bearing the highest viral loads. Importantly, GPgV could promote clinical manifestations of goose parvovirus infection, including reduced weight gain and 7% mortality. This finding contrasts with the lack of pathogenicity that is characteristic of previously reported pegiviruses.IMPORTANCE Members of the Pegivirus genus, family Flaviviridae, widely infect humans and other mammals, but are described as causing persistent infection and lacking pathogenicity. The efficiency of in vitro replication systems for pegivirus is poor, thus limiting investigation into viral replication steps. Because of that, the pathogenesis, cellular tropism, route of transmission, biology, and epidemiology of pegiviruses remain largely uncovered. Here, we report a phylogenetically distinct goose pegivirus (GPgV) that should be classified as a new species. GPgV proliferated in cell culture in a species- and cell-type-specific manner. Animal experiments show GPgV lymphotropism and promote goose parvovirus clinical manifestations. This study provides the first cell culture model for pegivirus, opening new possibilities for studies of pegivirus molecular biology. More importantly, our findings stand in contrast to the lack of identified pathogenicity of previously reported pegiviruses, which sheds lights on the pathobiology of pegivirus.
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Doenças das Aves , Infecções por Flaviviridae , Gansos/virologia , Pegivirus , Replicação Viral , Animais , Doenças das Aves/metabolismo , Doenças das Aves/virologia , Linhagem Celular , Infecções por Flaviviridae/metabolismo , Infecções por Flaviviridae/veterinária , Pegivirus/classificação , Pegivirus/fisiologiaRESUMO
There are rising concerns about microbes harboring antibiotic resistance genes (ARGs) and virulence-associated genes (VAGs) in humans and food-producing animals. Moreover, ARGs are considered as emerging environmental pollutants, posing probable life-threatening complications in humans and animals. Commensal Escherichia coli (E. coli) strain can carry a large number of VAGs, which may become opportunistic pathogen. The objective of this study was to determine the prevalence and possible association of ARGs and VAGs in E. coli isolates from clinically healthy waterfowls in China's tropical island, Hainan. For this purpose, 311 non-repeating E. coli isolates were evaluated for phenotypic drug resistance linked with ARGs. Additionally, strains were examined for subsequent resistance and virulence genes by uniplex or multiplex PCR and sequencing. Overall, 89 types of antibiotic resistance patterns were analysed, while 25 ARGs and 23 VAGs were observed, of which qnrS (99.4%) and iucD (99.7%) were the most commonly found genes, respectively. Significant positive associations were observed among ARGs and VAGs (p<0.05, OR>1). The strongest association between resistance and virulence gene was observed for qnrS and iss (OR, 76.25; 95% CI, 4.02-1445.42). Our results propose that waterfowls serve as a reservoir of E. coli carrying multi ARGs and various ExPEC associated VAGs. Therefore, this study provides necessary information on the occurrence and possible associations of ARGs and VAGs in healthy waterfowls, which may act as a reference for the regulatory use of antibiotics to stop the direct or indirect spread of these resistant and potential virulent microbes to natural environment.
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Antibacterianos/farmacologia , Doenças das Aves/microbiologia , Farmacorresistência Bacteriana , Patos , Infecções por Escherichia coli/veterinária , Escherichia coli/genética , Gansos , Animais , Animais Selvagens , China , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Escherichia coli/fisiologia , Infecções por Escherichia coli/microbiologia , Virulência/genéticaRESUMO
Forty-seven million people are living with memory-related disorders worldwide. Phytomedicines are gaining extensive interest in the treatment of these ailments. Memory-enhancing (acute and chronic) potentials of commercial grade extracts of Bacopa monnieri (200 mg/kg, po), Ginkgo biloba (150 mg/kg, po), and Lavandula angustifolia (200 mg/kg, po) and their mixture (B. monnieri 100 mg/kg, G. biloba 75 mg/kg, and L. angustifolia 100 mg/kg, po) were compared for their synergistic/additive effects on the Morris water maze (MWM) test and elevated plus maze (EPM) test in scopolamine-induced amnesia in mice. Escape latency and accumulative path length were significantly reduced both in acute (up to day 6) and chronic trials (days 8-14) in B. monnieri-, G. biloba-, and L. angustifolia-treated animals and their mixtures (n = 8, p < .05) in MWM. Furthermore, in probe trials (acute on day 7 and chronic on day 15), the number of crossing-overs at platform position and time spent in platform quadrant were significantly increased, while transfer latency in EPM was decreased in treated animals as compared to the saline group (n = 8, p < .05). The mixture showed synergistic effects on memory enhancement as compared to each extract individually in mice. Further studies may be carried out on the active compounds of B. monnieri at the cellular and molecular levels.
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A little over a year after the official announcement from the WHO, the COVID-19 pandemic has led to dramatic consequences globally. Today, millions of doses of vaccines have already been administered in several countries. However, the positive effect of these vaccines will probably be seen later than expected. In these circumstances, the rapid diagnosis of COVID-19 still remains the only way to slow the spread of this virus. However, it is difficult to predict whether a person is infected or not by COVID-19 while relying only on apparent symptoms. In this context, we propose to use machine learning (ML) algorithms in order to diagnose COVID-19 infected patients more effectively. The proposed diagnosis method takes into consideration several symptoms, such as flu symptoms, throat pain, immunity status, diarrhea, voice type, body temperature, joint pain, dry cough, vomiting, breathing problems, headache, and chest pain. Based on these symptoms that are modelled as ML features, our proposed method is able to predict the probability of contamination with the COVID-19 virus. This method is evaluated using different experimental analysis metrics such as accuracy, precision, recall, and F1-score. The obtained experimental results have shown that the proposed method can predict the presence of COVID-19 with over 97% accuracy.
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COVID-19 , Humanos , Aprendizado de Máquina , Pandemias , SARS-CoV-2 , Aprendizado de Máquina SupervisionadoRESUMO
OBJECTIVE: To determine the frequency of stroke and common factors leading to it after coronary artery bypass grafting. METHODS: This study was conducted at Cardiothoracic Surgery Department, Rehman Medical Institute, Peshawar. Study design was descriptive cross sectional study and the duration of the study was six months. The total sample size was 183 cases using 8.3% frequency of stroke after coronary artery bypass grafting, 95% confidence interval, 4% margin of error, using WHO sample size calculator. RESULTS: In this study mean age was 45 years with SD ± 1.26. Seventy five percent patients were male while 46(25%) females. Six patients (3%) patients had stroke while 177(97%) patients did not have any stroke. Among the six patients who were analyzed, all of them had Diabetes Mellitus and 50% patients had recent AMI, while only one patient had prior history of Atrial Fibrillation. CONCLUSIONS: Diabetes Mellitus is an independent risk factor for stroke after CABG surgery. whereas, recent MI is also associated with increased incidence of stroke in post CABG patients.
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OBJECTIVE: To find the incidence of intra-aortic balloon pump (IABP) induction and factors associated with its insertion in coronary artery bypass grafting (CABG). METHODS: This retrospective observational non interventional study was conducted at Cardiac Surgery Department, North West General Hospital and Research Center, Peshawar from December 2018 to March 2020. The total sample size was 360 patients who underwent coronary artery bypass grafting (CABG). The research was piloted in the cardiac operation theatre then cardiac intensive care unit (CICU) of Northwest General Hospital and Research center Hayatabad Peshawar. Data was collected from 360 patients scheduled for CABG. Total numbers of patients in whom IABP was inserted and factors associated with IABP insertions were noted. All the information was collected on a specifically prepared Form. Data was entered and evaluated in statistical package for social sciences form 25. RESULTS: In this study, a total of 360 patients were observed who underwent coronary artery bypass grafting (CABG). We determined the frequency of IABP induction and the factors related to it. Gender distribution among patients who were assisted with IABP was 43% female and 57% male. IABP induction was done for most of moderately to severely reduced ejection fraction patients. Other factors related to patients who required IABP support were previous myocardial infarction 100%, hypertension 86%, diabetes mellitus 64%, coronary end-arterectomy 21% and smoking 7%. The results were analyzed. We have used the (SPSS) version 25 and Chi-square test for analysis in which the P-value less than 0.00001 is statistically significant. CONCLUSION: Incidence of insertion of IABP among CABG population was 3.9% in our hospital. It is an essential support to post CABG patient with left ventricular dysfunction after cardiopulmonary bypass with moderate to severely reduced ejection fraction, Myocardial infarction, hypertension, diabetes mellitus. Smoking and endarterectomy were not significantly related to IABP induction in our study. Multicenter study is still required to find out the other factors governing the IABP insertion.
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BACKGROUND: Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models. METHODS: In this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies. RESULTS: Compared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies. CONCLUSIONS: Our results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against TMUV infection in ducks than the homologous prime-boost strategies, suggesting that the heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV.
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Anticorpos Antivirais/sangue , Flavivirus/imunologia , Imunização Secundária/métodos , Imunização Secundária/veterinária , Vacinas Virais/imunologia , Adenoviridae , Animais , Anticorpos Neutralizantes/sangue , Citocinas/imunologia , Patos/imunologia , Imunidade Celular , Imunidade Humoral , Salmonella , Vacinas de DNA/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Carga Viral , Vacinas Virais/administração & dosagemRESUMO
BACKGROUND: eIF2α is a regulatory node that controls protein synthesis initiation by its phosphorylation or dephosphorylation. General control nonderepressible-2 (GCN2), protein kinase R-like endoplasmic reticulum kinase (PERK), double-stranded RNA (dsRNA)-dependent protein kinase (PKR) and heme-regulated inhibitor (HRI) are four kinases that regulate eIF2α phosphorylation. MAIN BODY: In the viral infection process, dsRNA or viral proteins produced by viral proliferation activate different eIF2α kinases, resulting in eIF2α phosphorylation, which hinders ternary tRNAMet-GTP-eIF2 complex formation and inhibits host or viral protein synthesis. The stalled messenger ribonucleoprotein (mRNP) complex aggregates under viral infection stress to form stress granules (SGs), which encapsulate viral RNA and transcription- and translation-related proteins, thereby limiting virus proliferation. However, many viruses have evolved a corresponding escape mechanism to synthesize their own proteins in the event of host protein synthesis shutdown and SG formation caused by eIF2α phosphorylation, and viruses can block the cell replication cycle through the PERK-eIF2α pathway, providing a favorable environment for their own replication. Subsequently, viruses can induce host cell autophagy or apoptosis through the eIF2α-ATF4-CHOP pathway. CONCLUSIONS: This review summarizes the role of eIF2α in viral infection to provide a reference for studying the interactions between viruses and hosts.
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Fator de Iniciação 2 em Eucariotos/genética , Interações Hospedeiro-Patógeno/genética , Viroses/genética , Replicação Viral/genética , Humanos , Fosforilação , Processamento de Proteína Pós-Traducional , RNA Viral/genética , Proteínas Virais/genéticaRESUMO
BACKGROUND: Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses. MAIN BODY: The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion. CONCLUSIONS: Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.
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Interações entre Hospedeiro e Microrganismos/imunologia , Proteínas Imediatamente Precoces/genética , Evasão da Resposta Imune , Ribonucleases/genética , Proteínas Virais/genética , Animais , Linhagem Celular , Chlorocebus aethiops , Expressão Gênica , Herpesvirus Humano 1 , Interações entre Hospedeiro e Microrganismos/genética , Proteínas Imediatamente Precoces/metabolismo , Ribonucleases/metabolismo , Células Vero , Proteínas Virais/metabolismo , Vírion/genética , Replicação ViralRESUMO
BACKGROUND: pUL21 is a conserved protein of Alphaherpesvirinae that performs multiple important functions. The C-terminus of pUL21 in other members of this subfamily has RNA-binding ability; this domain contributes to pseudorabies virus (PRV) retrograde axonal transport in vitro and in vivo and participates in newly replicated viral DNA packaging and intracellular virus transport. However, knowledge regarding duck enteritis virus (DEV) pUL21 is limited. RESULTS: We verified that DEV UL21 is a γ2 gene that encodes a structural protein. Moreover, we observed that pUL21 localized to the nucleus and cytoplasm. DEV pUL21 interacted with pUL16 and formed a complex in transfected human embryonic kidney (HEK) 293 T cells and DEV-infected duck embryo fibroblasts (DEFs). These results were further confirmed by CO-IP assays. CONCLUSIONS: The DEV UL21 gene is a late gene, and pUL21 localizes to the nucleus and cytoplasm. DEV UL21 is a virion component. In addition, pUL21 can interact with pUL16. These findings provide insight into the characteristics of UL21 and the interaction between pUL21 and its binding partner pUL16. Our study enhances the understanding of DEV pUL21.
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Mardivirus/genética , Mardivirus/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Células Cultivadas , Patos/virologia , Fibroblastos , Regulação Viral da Expressão Gênica , Células HEK293 , Infecções por Herpesviridae/veterinária , Humanos , Doenças das Aves Domésticas/virologia , Vírion , Replicação ViralRESUMO
Fungicide thiram, a representative dithiocarbamate pesticide can cause potential health hazards to humans and animal health due to the residues in various agricultural products. However, the effects of thiram on lipid metabolism by perturbing gut microbiota of chickens are not clear. Our study was aimed to explore the protective of polysaccharide extracted from Morinda officinalis (MOP) on acute thiram-exposed chickens, and to analyze the association between alteration of gut microbiota and lipid metabolism. Three hundred chicks are fed with a normal diet, thiram-treated diet (100 mg/kg), and a thiram-treated diet supplemented with 250, 500, or 1000 mg/kg MOP was used in this study, respectively. The results showed that thiram exposure prominently elevated liver index, changed liver function by histopathological examination and serum biochemistry diagnoses, and increased blood lipid parameters. Meanwhile, the expression level of some key genes in hepatic lipid metabolism dysregulated significantly in the thiram-exposed chickens. Furthermore, 16S rRNA gene sequencing indicated that thiram exposure can significantly alter the richness, diversity, and composition of the broiler fecal microbiota, and the relative abundance of Firmicutes and Proteobacteria was also affected at the phylum level. In addition, some microbial populations including Lactobacillus, Ruminococcus, Oscillospira, Blautia, and Butyricicoccus significantly decreased at the genus level, whereas the Klebsiella was opposite. Correlation analysis further revealed a significant association between microorganisms and lipid metabolism-related parameters. Optimistically, 500 mg/kg MOP can alleviate the damage of thiram in the gut and liver. Together, these data suggest that thiram exposure causes the imbalance of the gut microbiota and hepatic lipid metabolism disorder in chickens.
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Galinhas/metabolismo , Fungicidas Industriais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Tiram/toxicidade , Animais , Fezes/microbiologia , Fígado/metabolismo , Testes de Função Hepática , Morinda/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , RNA Ribossômico 16S/metabolismoRESUMO
OBJECTIVE: The aim of our study is to analyze the characteristics, morbidity and mortality of patients requiring an Intra-Aortic Balloon Pump (IABP) in Coronary Artery Bypass Grafting (CABG). METHODS: An analysis was done on the prospectively collected data of 1216 patients who had CABG in our center between July, 2017 and May, 2019 at our hospital. We categorized patients in to an IABP and non-IABP group on the basis of IABP use. We then compared the pre-operative, per-operative and post-operative characteristics of the two groups. We further stratified the patients according to pre-op ejection fraction (EF). RESULTS: Out of 1216 patients, 135(11.10%) patients required an IABP. 70(51.9%) patients of IABP group and 699(64.7%) patients of non-IABP group had hypertension (p-value 0.0036). 23.0% had previous myocardial infarction (MI) in the IABP group and 13.8% had prior myocardial infarction (MI) in non-IABP group (p-value 0.0463). Among the patients requiring an IABP, 21(15.5%) of patients had normal EF (>50%) (P-value<0.0001), 72 (53.3%) had EF 35-50%, and 41(30.3%) patients had EF<35% (p-value <0.0001). Mortality of IABP group (19.3%) was greater than non-IABP group (2.4%) (P-value 0.00001). CONCLUSIONS: Use of IABP increased as the EF decreased. Rate of post-operative stroke, prolonged ICU stay, prolonged ventilation, re-opening due to bleeding and mortality was seen to be significantly higher in the IABP group.
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BACKGROUND AND OBJECTIVES: Patients with low ejection fraction undergoing isolated CABG surgery are at a higher risk for postoperative complications and mortality. This study was conducted to evaluate the impact of ejection fraction on the outcome of isolated Coronary Artery Bypass Grafting (CABG). METHODS: Between July, 2017 to May, 2019 total 1214 patients underwent isolated CABG. Patients were divided into three groups based on their pre-operative Ejection Fraction (EF). Group-I included 625 patients with EF >50% [Normal EF], Group-II included 484 patients with EF 35-50% [Mild to Moderately Reduced EF], and Group 3 included 105 patients with EF<35% [Severely Reduced EF]. RESULTS: The mean age of Group-I was 57.58 ± 9.206, Group-II was 58.38±9.124 and Group-III was 58.81± 8.663. The male gender was the predominant gender in all three groups: 194(41.1%) in Group-I, 201(52.6%) in Gp2, 52 (61.9%) in Group-III. 231(36.9) patients in Group-I, 234(48.3)in Group-II and 59(56.2) in Group-III had raised creatinine pre operatively. 5(0.8%) patients in Group-I, 2(0.4%) in Group-II and 3(2.9%) in Group-III had history of CVA. Hypertension was present in approximately 60% of all our patients. In the per-operative period 20(3.2%) patients in Group-I required an IABP as compared to 73(15.1%) in Group-II and 41(39.0%) in Group-III. The mean post-operative mortality in Group-I was 19 (3%), Group-II was 24(5.0%) and low EF group was 9(8.6%). CONCLUSIONS: The results clearly indicate that worsening pre-operative ejection fraction is associated with a higher mortality post-operatively in patients undergoing isolated CABG. In addition, use of IABP increases as pre-operative LVEF decreases.