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1.
Annu Rev Immunol ; 36: 43-71, 2018 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-29144838

RESUMEN

Human T cell leukemia virus type 1 (HTLV-1), also known as human T lymphotropic virus type 1, was the first exogenous human retrovirus discovered. Unlike the distantly related lentivirus HIV-1, HTLV-1 causes disease in only 5-10% of infected people, depending on their ethnic origin. But whereas HIV-1 infection and the consequent diseases can be efficiently contained in most cases by antiretroviral drug treatment, there is no satisfactory treatment for the malignant or inflammatory diseases caused by HTLV-1. The purpose of the present article is to review recent advances in the understanding of the mechanisms by which the virus persists in vivo and causes disabling or fatal diseases.


Asunto(s)
Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/fisiología , Animales , Susceptibilidad a Enfermedades , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad , Inmunidad Celular , Interferón Tipo I/metabolismo , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Proteínas Reguladoras y Accesorias Virales/genética , Proteínas Reguladoras y Accesorias Virales/inmunología , Proteínas Reguladoras y Accesorias Virales/metabolismo , Latencia del Virus/inmunología
2.
Rev Med Virol ; 34(4): e2567, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38937135

RESUMEN

Human T-lymphotropic virus type-1 (HTLV-1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T-cell leukaemia/lymphoma malignancy and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro-myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV-1-associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV-1-infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV-1 a natural probe for the study of malignancy and neuro-inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV-1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro-inflammatory propensity of HTLV-1-induced HAM/TSP. Such an emphasis on the virus-host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV-1 therapeutics.


Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Virus Linfotrópico T Tipo 1 Humano/fisiología , Paraparesia Espástica Tropical/virología , Paraparesia Espástica Tropical/inmunología , Infecciones por HTLV-I/virología , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/complicaciones , Interacciones Huésped-Patógeno/inmunología , Animales , Interacciones Microbiota-Huesped/inmunología
3.
Cancer Sci ; 115(1): 310-320, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37950425

RESUMEN

Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Paraparesia Espástica Tropical , Adulto , Humanos , Virus Linfotrópico T Tipo 1 Humano/genética , Provirus/genética , Biomarcadores , Carga Viral
4.
J Bioenerg Biomembr ; 56(1): 15-29, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38064155

RESUMEN

Cytosolic-free calcium ions play an important role in various physical and physiological processes. A vital component of neural signaling is the free calcium ion concentration often known as the second messenger. There are many parameters that effect the cytosolic free calcium concentration like buffer, voltage-gated ion channels, Endoplasmic reticulum, Mitochondria, etc. Mitochondria are small organelles located within the nervous system that are involved in processes within cells such as calcium homeostasis management, energy generation, response to stress, and cell demise pathways. In this work, a mathematical model with fuzzy boundary values has been developed to study the effect of Mitochondria and ER fluxes on free Calcium ions. The intended findings are displayed utilizing the physiological understanding that amyloid beta plaques and tangles of neurofibrillary fibers have been identified as the two main causes of AD. The key conclusion of the work is the investigation of [Formula: see text] for healthy cells and cells affected by Alzheimer's disease, which may aid in the study of such processes for computational scientists and medical practitioners. Also, it has been shown that when a unique solution is found for a specific precise problem, it also successfully deals with any underlying ambiguity within the problem by utilizing a technique based on the principles of linear transformation. Furthermore, the comparison between the analytical approach and the generalized hukuhara derivative approach is shown here, which illustrates the benefits of the analytical approach. The simulation is carried out in MATLAB.


Asunto(s)
Péptidos beta-Amiloides , Calcio , Péptidos beta-Amiloides/metabolismo , Calcio/metabolismo , Mitocondrias/metabolismo , Retículo Endoplásmico/metabolismo , Neuronas/metabolismo , Señalización del Calcio
5.
Cytokine ; 182: 156710, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39089216

RESUMEN

BACKGROUND: Human T-lymphotropic virus (HTLV-1) is a neglected virus with worldwide distribution of over 10 million people and is the cause of two main associated diseases Adult T cell Leukemia-Lymphoma (ATLL), and HTLV-1-associated Myelopathy/Tropical Spastic paraparesis (HAM/TSP). The IL-17 cytokine family plays a crucial role in the host immunity against HTLV-1 and the development of associated disease. A systematic review was conducted to analyze all research reporting on the levels or expression of the IL-17 HTLV-1 infection and associated diseases. METHODS: The literature search was conducted in electronic databases including PubMed/Medline and Web of Sciences until January 31st, 2024, followed by the PRISMA guidelines. RESULTS: Our search revealed 20 eligible articles to be included in our study. The total number of cases studied was 1420, of which 386 were carriers without any symptoms, and were 176 ATLL and 237 HAM/TSP. The IL-17 cytokine family production or mRNA expression was higher in HAM/TSP patients but showed a trend toward reduction in the case of ATLL. CONCLUSIONS: Our results showed that while The IL-17 cytokine family plays a significant role in the immunopathogenesis of disease and clinical status of patients with inflammatory disorders such as HAM/TSP, IL-17 production is diminished and the RORC/IL-17 signaling pathway is downregulated during ATLL. Our data suggest that boosting the RORC/IL-17 signaling pathway in ATLL and using anti-IL-17 agents in HAM/TSP and other HTLV-related inflammatory conditions might benefit patients and improve their outcomes.

6.
J Fluoresc ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878194

RESUMEN

Nitrite ion is one of the materials widely used in human life, and the accurate, sensitive and stable detection of nitrite ions is of great significance to people's healthy life. In this study, nitrogen-doped fluorescent carbon dots (N-CDs) for detecting nitrite salt solutions were prepared using citric acid monohydrate and Chrysoidin as precursors through a one-pot hydrothermal method. Under the condition of pH = 3, a noticeable quenching phenomenon occurred in the carbon dot solution with the increase in nitrite ion concentration. This quenching effect might be attributed to the diazonium effect. N-CDs have been successfully used as fluorescence probes for NO2- detection. NO2- can effectively quench the fluorescence intensity of N-CDs, providing a linear response to fluorescence quenching efficiency with respect to NO2- concentration within the range of 0-10µM and 10-30µM, and a detection limit of 52nM, showing high sensitivity. In addition, the probe was applied to the determination of NO2- in ham sausage samples with a detection limit of 0.67µM and recoveries in the range of 99.5-102.3%, the fluorescent probe showed satisfactory reliability.

7.
Brain ; 146(8): 3181-3191, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37093965

RESUMEN

Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1 or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, CSF inflammatory markers and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and four (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (P = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effects on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment.


Asunto(s)
Personas con Discapacidad , Virus Linfotrópico T Tipo 1 Humano , Trastornos Motores , Paraparesia Espástica Tropical , Humanos , Paraparesia Espástica Tropical/tratamiento farmacológico
8.
CNS Spectr ; 29(3): 206-214, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38685594

RESUMEN

OBJECTIVE: Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD). METHODS: Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data. RESULTS: At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: -2.73 [-3.63, -1.82], p < 0.0001) and amotivation scores (mean, 95% CI: -0.78 [-1.04, -0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time. CONCLUSION: This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.


Asunto(s)
Anhedonia , Trastorno Depresivo Mayor , Clorhidrato de Venlafaxina , Humanos , Clorhidrato de Venlafaxina/uso terapéutico , Clorhidrato de Venlafaxina/administración & dosificación , Clorhidrato de Venlafaxina/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Anhedonia/efectos de los fármacos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Motivación , Antidepresivos de Segunda Generación/uso terapéutico , Antidepresivos de Segunda Generación/administración & dosificación , Ciclohexanoles/uso terapéutico , Ciclohexanoles/administración & dosificación , Resultado del Tratamiento , Método Doble Ciego
9.
Mol Ther ; 31(7): 2266-2285, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-36934299

RESUMEN

The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell leukemia (ATL). Worldwide, more than 10 million people are infected and approximately 5% of these individuals will develop ATL, a highly aggressive cancer that is currently incurable. In the last years, genome editing tools have emerged as promising antiviral agents. In this proof-of-concept study, we use substrate-linked directed evolution (SLiDE) to engineer Cre-derived site-specific recombinases to excise the HTLV-1 proviral genome from infected cells. We identified a conserved loxP-like sequence (loxHTLV) present in the long terminal repeats of the majority of virus isolates. After 181 cycles of SLiDE, we isolated a designer-recombinase (designated RecHTLV), which efficiently recombines the loxHTLV sequence in bacteria and human cells with high specificity. Expression of RecHTLV in human Jurkat T cells resulted in antiviral activity when challenged with an HTLV-1 infection. Moreover, expression of RecHTLV in chronically infected SP cells led to the excision of HTLV-1 proviral DNA. Our data suggest that recombinase-mediated excision of the HTLV-1 provirus represents a promising approach to reduce proviral load in HTLV-1-infected individuals, potentially preventing the development of HTLV-1-associated diseases.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Adulto , Humanos , Virus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/tratamiento farmacológico , Paraparesia Espástica Tropical/genética , Provirus/genética , Antivirales
10.
Food Microbiol ; 119: 104433, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38225045

RESUMEN

A quantitative microbiological spoilage risk assessment model (QMSRA) for cooked ham sliced at retail was developed based on a stochastic growth model for lactic acid bacteria (LAB), which are considered as the specific spoilage organisms (SSO), and a "spoilage-response" relationship characterizing the variability in consumer's perception of spoilage. In a simulation involving 10,000 cooked ham purchases, the QMSRA model predicted a median of zero spoilage events for up to 4.5 days of storage. After storage times of 5 and 6 days, the model predicted 1,790 and 8,570 spoilage events, respectively. A sensitivity analysis showed that domestic storage temperature was the most significant factor affecting LAB concentration in cooked ham, followed by the LAB contamination level at slicing. A scenario analysis was performed testing better temperature control of consumer's refrigerators, better hygiene conditions during slicing and a combination of the two strategies. Among the tested scenarios, a 2 log reduction in the LAB contamination at slicing combined with a 2 °C decrease in domestic storage temperature resulted in zero risk of spoilage for up to 12 days of storage. The QMSRA model developed in the present study can be a useful tool for quality management decisions.


Asunto(s)
Lactobacillales , Productos de la Carne , Microbiología de Alimentos , Culinaria , Temperatura , Medición de Riesgo , Productos de la Carne/microbiología , Recuento de Colonia Microbiana
11.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33649182

RESUMEN

HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10-9) and class II (P = 1.21 × 10-8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10-5), HLA-B*07:02 (P = 4.97 × 10-10), HLA-DRB1*01:01 (P = 1.15 × 10-9) and HLA-DQB1*05:01 (P = 2.30 × 10-9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10-5), HLA-DRB1*15:01 (P = 1.06 × 10-5) and HLA-DQB1*06:02 (P = 1.78 × 10-6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10-10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.


Asunto(s)
Estudio de Asociación del Genoma Completo , Antígenos HLA/genética , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Paraparesia Espástica Tropical/genética , Mapeo Cromosómico , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Japón , Polimorfismo de Nucleótido Simple , Carga Viral
12.
J Sci Food Agric ; 104(2): 1030-1038, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37721428

RESUMEN

BACKGROUND: Tumbling treatment is widely used in the production of cooked ham. However, traditional intermittent tumbling (IT) treatment is time-consuming. To enhance the tumbling efficiency, high-intensity ultrasound was used to assist IT treatment (UIT). RESULTS: UIT treatment reduced the tumbling time and significantly improved the water holding capacity, tenderness, sliceability and texture of cooked ham compared to IT treatment. Furthermore, more violent destruction of meat tissue was exhibited in the UIT treatment. This change facilitated extraction of more salt-soluble protein, which in turn welded meat pieces tightly and improved the quality of the cooked ham. CONCLUSION: UIT treatment could accelerate the tumbling process and enhance the quality of cooked ham. These results may provide guidance on effective strategies for a high-quality meat production process. © 2023 Society of Chemical Industry.


Asunto(s)
Productos de la Carne , Productos de la Carne/análisis , Culinaria/métodos , Carne , Músculos , Cloruro de Sodio
13.
Med J Armed Forces India ; 80(2): 145-152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525466

RESUMEN

Background: Smoking is common in patients of depression and is known to affect response to antidepressants. This study was undertaken to evaluate the effect of smoking on the antidepressant effect of sertraline. Method: Patients with depression were divided into smoker and nonsmoker cohorts and followed up for 8 weeks. Serum sertraline levels were estimated using the high-performance liquid chromatography system. Response to treatment was evaluated with the Hamilton Depression Rating Scale (HAM-D). Results: Serum sertraline levels did not differ between smokers and nonsmokers at 4 and 8 weeks. Nonsmokers responded better to sertraline than smokers after 8 weeks. Adverse drug reaction profile did not vary between the two groups and was not impacted by serum sertraline levels. Nonsmokers showed a greater fall in the HAM-D score than smokers. Conclusion: This study found depression among smokers to be less responsive to sertraline. This was not explained by serum sertraline levels. Treatment of depression in smokers with sertraline might require higher doses and duration, with more frequent reviews.

14.
Clin Infect Dis ; 77(6): 851-856, 2023 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-37157862

RESUMEN

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurological condition characterized by progressive myelopathic symptoms including spasticity, pain, weakness, and urinary symptoms, without proven treatments. Mogamulizumab (MOG) is a monoclonal antibody that binds CCR4 and leads to the clearance of HTLV-1-infected CCR4+ cells. A phase 1-2a study in Japan evaluated MOG for the treatment of HAM/TSP and reported decreases in HTLV-1 proviral load and neuroinflammatory markers, with clinical improvement in some participants. METHODS: We administered MOG 0.1 mg/kg every 8 weeks to individuals with HAM/TSP as a compassionate and palliative treatment. Patients who received MOG had (1) a positive peripheral HTLV-1 antibody, (2) progressive myelopathic symptoms, and (3) a diagnosis of HAM/TSP. RESULTS: Four female patients, ages 45-68, received MOG (range, 2-6 infusions) between 1 November 2019 and 30 November 2022. Two patients with <3 years of symptoms had milder disease, with Osame scores <4. The other 2, with >7 years of symptoms, had Osame scores >5. One patient, with 6 total treatments, received dose-reduced MOG after she developed a rash at the initial dose. The 2 patients with milder baseline disease reported symptomatic improvement and saw reductions in Osame and/or modified Ashworth scale scores during follow-up. The other 2 patients showed no improvement. All 4 developed rashes after receiving MOG-a treatment-limiting event in some cases. CONCLUSIONS: Clinical trials are needed including diverse patient populations to assess the potential role of MOG for HAM/TSP. Our findings may help inform the development of these trials.


Asunto(s)
Exantema , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Femenino , Paraparesia Espástica Tropical/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Carga Viral
15.
Eur J Neurosci ; 58(3): 2662-2676, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37414581

RESUMEN

FKBP5 is an important stress-regulatory gene implicated in stress-related psychiatric diseases. Single nucleotide polymorphisms of the FKBP5 gene were shown to interact with early life stress to alter the glucocorticoid-related stress response and moderate disease risk. Demethylation of cytosine-phosphate-guanine-dinucleotides (CpGs) in regulatory glucocorticoid-responsive elements was suggested to be the mediating epigenetic mechanism for long-term stress effects, but studies on Fkbp5 DNA methylation (DNAm) in rodents are so far limited. We evaluated the applicability of high-accuracy DNA methylation measurement via targeted bisulfite sequencing (HAM-TBS), a next-generation sequencing-based technology, to allow a more in-depth characterisation of the DNA methylation of the murine Fkbp5 locus in three different tissues (blood, frontal cortex and hippocampus). In this study, we not only increased the number of evaluated sites in previously described regulatory regions (in introns 1 and 5), but also extended the evaluation to novel, possibly relevant regulatory regions of the gene (in intron 8, the transcriptional start site, the proximal enhancer and CTCF-binding sites within the 5'UTR). We here describe the assessment of HAM-TBS assays for a panel of 157 CpGs with possible functional relevance in the murine Fkbp5 gene. DNAm profiles were tissue-specific, with lesser differences between the two brain regions than between the brain and blood. Moreover, we identified DNAm changes in the Fkbp5 locus after early life stress exposure in the frontal cortex and blood. Our findings indicate that HAM-TBS is a valuable tool for broader exploration of the DNAm of the murine Fkbp5 locus and its involvement in the stress response.


Asunto(s)
Metilación de ADN , Glucocorticoides , Animales , Ratones , Sulfitos , Epigénesis Genética
16.
J Neurovirol ; 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37531001

RESUMEN

There is an urgent need to find an effective therapy for life-threatening HTLV-1-associated diseases. Bitter melon (Momordica charantia) is considered a traditional herb with antiviral and anticancer properties and was tested in this study on HTLV-1 infectivity. GC-MS analyzed the alcoholic extract. In vitro assay was carried out using transfection of HUVEC cells by HTLV-1-MT2 cell line. The cells were exposed to alcoholic and aqueous extracts at 5,10, and 20 µg/mL concentrations. In vivo, mice were divided into four groups. Three groups were treated with HTLV-1-MT-2 cells as test groups and positive control, and PBS as the negative control group in the presence and absence of M. charantia extracts. Peripheral blood mononuclear cells (PBMCs), mesenteric lymph nodes (MLNs), and splenocytes were collected for HTLV-1-proviral load (PVL) assessment, TaqMan-qPCR. The GC-MS analysis revealed 36 components in M. charantia. The studies showed significant reductions in HTLV-1-PVL in the presence of extract in the HUVEC-treated groups (P = 0.001). Furthermore, the inhibitory effects of extracts on HTLV-1 infected mice showed significant differences in HTLV-1-PVL among M. charantia treated groups with untreated (P = 0.001). The T-cells in MLNs were significantly more susceptible to HTLV-1 than others (P = 0.001). There were significant differences among HTLV-1-infected cells in MLNs and splenocytes (P = 0.001 and 0.046, respectively). Also, aqueous and alcoholic extract-treated groups significantly affected HTLV-1-infected PBMCs (P = 0.002 and 0.009, respectively). M. charantia may have effective antiviral properties. The substantial compound of M. charantia could have inhibitory effects on the proliferation and transmission of HTLV-1 oncovirus.

17.
Crit Rev Food Sci Nutr ; 63(27): 8781-8795, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35373656

RESUMEN

Foul-smelling odors are main quality defects of dry-cured ham, which are connected with the excessive degradation of the structural proteins and excessive oxidation of lipids caused by the abnormal growth of spoilage microorganisms, threatening the development of dry-cured ham industry. Characterizing the key microorganisms and metabolites resulted in the spoilage of dry-cured ham, and discussing the relationship between spoilage microorganisms and metabolites are the key aspects to deeply understand the formation mechanism of off-odor in dry-cured ham. Until now, there is no detailed discussion or critical review on the role of spoilage microorganisms in developing the off-odor of dry-cured ham, and the regulation of off-odor and spoilage microorganisms by starter cultures has been not discussed. This review shows the recent achievement in the off-odor formation mechanism of dry-cured ham, and outlines the potential regulation of off-odor defects in dry-cured ham by starter cultures. Results from current research show that the abnormal growth of Lactic acid bacteria, Micrococcaceae, Enterobacteriaceae, Yeasts and Molds plays a key role in developing the off-odor defects of dry-cured ham, while the key spoilage microorganisms of different type hams are discrepant. High profile of aldehydes, acids, sulfur compounds and biogenic amines are responsible for off-odor development in spoiled dry-cured ham. Several starter cultures derived from these species of Staphylococcus, Penicillium, Debaryomyces, Pediococcus and Lactobacillus show a great potential to prevent microbiological hazards and improve flavor quality of dry-cured ham, whereas, the ecology, function and compatibility of these starter cultures with the processing parameters of dry-cured ham need to be further evaluated in the future.


Asunto(s)
Productos de la Carne , Penicillium , Carne de Cerdo , Odorantes , Penicillium/metabolismo , Lactobacillus , Olfato , Productos de la Carne/microbiología
18.
Crit Rev Food Sci Nutr ; : 1-17, 2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38069684

RESUMEN

Traditional dry cured ham (DCH) is favored by consumers for its distinctive flavor, derived from an array of volatile organic compounds (VOCs). Microbiota play a pivotal role in the formation of VOCs. To fully comprehend the pathway by which the microbiota enhance the flavor quality of DCH, it is imperative to elucidate the flavor profile of DCH, the structural and metabolic activities of the microbiota, and the intricate relationship between microbial and VOCs. Thus far, the impact of microbiota on the flavor profile of DCH has not been comprehensively discussed or reviewed, and the succession of bacteria, especially at distinct phases of processing, has not been adequately summarized. This article aims to encapsulate the considerable potential of ferments in shaping the flavor characteristics of DCH, while elucidating the underlying mechanisms through which VOCs are generated in hams via microbial metabolism. Throughout the various stages of DCH processing, the composition of microbiota undergoes dynamic changes. Furthermore, they directly participate in the formation of VOCs in DCH through the catabolism of amino acids, metabolism of fatty acids, and the breakdown of carbohydrates. Several microorganisms, including Lactobacillus, Penicillium, Debaryomyces, Pediococcus, and Staphylococcus, exhibit considerable potential as fermenters in ham production.

19.
Nanotechnology ; 34(21)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36808909

RESUMEN

This work addresses a theoretical exploration of the water-based hybrid nanofluid flow over a nonlinear elongating surface. The flow is taken under the effects of Brownian motion and thermophoresis factors. Additionally, the inclined magnetic field is imposed in the present study to investigate the flow behavior at different angle of inclination. Homotopy analysis approach is used for the solution of modeled equations. Various physical factors, which are encountered during process of transformation, have been discussed physically. It is found that the magnetic factor and angle of inclination have reducing impacts on the velocity profiles of the nanofluid and hybrid nanofluid. The nonlinear index factor has direction relation with the velocity and temperature of the nanofluid and hybrid nanofluid flows. The thermal profiles of the nanofluid and hybrid nanofluid are augmented with the increasing thermophoretic and Brownian motion factors.CuO-H2Onanofluid flow has enhanced heat transfer rate thanAg-H2Onanofluid flow. On the other hand, theCuO-Ag/H2Ohybrid nanofluid has better thermal flow rate thanCuO-H2OandAg-H2Onanofluids. From this table it has noticed that, Nusselt number has increased by 4% for silver nanoparticles whereas for hybrid nanofluid this incrimination is about 15%, which depicts that Nusselt number is higher for hybrid nanoparticles.

20.
Nanotechnology ; 34(42)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37473745

RESUMEN

The present article examines the consequences of a magnetic field, Hall current, and thermal radiation on the spinning flow of hybrid nanofluid (HNF) across a revolving disc. The core objective of the study is to improve the energy transference rate through hybrid nano liquid for industrial and engineering operations. The HNFs have advanced thermophysical characteristics. Therefore, in the current study, a superior class of nanomaterials (carbon nanotubes (CNTs) and Al2O3) are added to the base fluid. The modeled equations are demoted to a dimensionless set of Ordinary differential equations (ODEs) through similarity conversion and are analytically solved by engaging the homotopy analysis method. The physical constraints' effect on energy, velocity, motile microorganism, and mass profiles have been drawn and discussed. For accuracy, the results are compared to the published studies, which ensures the accuracy and reliability of the technique and results. It is observed that the energy communication rate lessens with the flourishing values of thermal radiation and for Hall current. Furthermore, it is noted that due to its carbon-carbon bonding in CNTs, it has a greater tendency for energy propagation than Al2O3nanoparticles.

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