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1.
Sci Rep ; 14(1): 15501, 2024 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969681

RESUMEN

Late blight is a serious disease of potato worldwide. Our study aimed to unveil genes involved in late blight resistance in potato by RNA-seq analysis after artificial inoculation under controlled conditions. In this study, two potato somatic hybrids (P7 and Crd6) and three varieties such as Kufri Girdhari, Kufri Jyoti and Kufri Bahar (control) were used. Transcriptiome analysis revealed statistically significant (p < 0.05) differentially expressed genes (DEGs), which were analysed into up-regulated and down-regulated genes. Further, DEGs were functionally characterized by the Gene Ontology annotations and the Kyoto Encyclopedia of Genes and Genomes pathways. Overall, some of the up-regulated genes in resistant genotypes were disease resistance proteins such as CC-NBS-LRR resistance protein, ankyrin repeat family protein, cytochrome P450, leucine-rich repeat family protein/protein kinase family, and MYB transcription factor. Sequence diversity analysis based on 38 peptide sequences representing 18 genes showed distinct variation and the presence of three motifs in 15 amino acid sequences. Selected genes were also validated by real-time quantitative polymerase chain reaction analysis. Interestingly, gene expression markers were developed for late blight resistant genotypes. Our study elucidates genes involved in imparting late blight resistance in potato, which will be beneficial for its management strategies in the future.


Asunto(s)
Resistencia a la Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas , Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/microbiología , Solanum tuberosum/inmunología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/genética , Transcriptoma , Genes de Plantas , Genotipo
2.
J Biochem ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960390

RESUMEN

Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g., hyperglycemia or hypercholesterolemia) increase erythrocyte adhesion to various ECM components, potentially through altering glycosaminoglycans (GAGs). In this study, we have investigated the expression of syndecan (Sdc) family members that could be involved in mediating cytoadherence under conditions of dyslipidemia and hyperglycemia. Among the Sdc family members analyzed, we found significant overexpression of Sdc-3 in erythrocyte membranes harvested from high-fat-fed control and diabetic animals. Animal studies revealed a positive correlation between Sdc-3 expression, blood sugar levels, and erythrocyte adhesion. In the human study, diabetic cohorts with BMI >24.9 showed significantly increased expression of Sdc-3. Interestingly, blocking the Sdc-3 moiety with an anti-Sdc-3 antibody revealed that the core protein might not be directly involved in erythrocyte adhesion to fibronectin despite the GAGs bringing about adhesion. Lastly, Nano LC-MS/MS verified the presence of Sdc-3 in erythrocyte membranes. In conclusion, the high-fat diet and diabetes modulated Sdc-3 expression in the erythrocyte membrane, which may alter its adhesive properties and promote vascular complications.

3.
Nat Med ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961225

RESUMEN

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment. This phenotype is defined by increased interleukin (IL)-17 and IL-1 coexpressed gene modules in blood neutrophils and in microglia of cognitively impaired female APOE ε4 carriers, showing increased infiltration to the AD brain. APOE4 female IL-17+ neutrophils upregulated the immunosuppressive cytokines IL-10 and TGFß and immune checkpoints, including LAG3 and PD-1, associated with accelerated immune aging. Deletion of APOE4 in neutrophils reduced this immunosuppressive phenotype and restored the microglial response to neurodegeneration, limiting plaque pathology in AD mice. Mechanistically, IL-17F upregulated in APOE4 neutrophils interacts with microglial IL-17RA to suppress the induction of the neurodegenerative phenotype, and blocking this axis supported cognitive improvement in AD mice. These findings provide a translational basis to target IL-17F in APOE ε4 female carriers with cognitive impairment.

4.
Med Chem ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38982919

RESUMEN

BACKGROUND: Among various carboxylic acid derivatives, valeric acid or pentanoic acid is found to be widely distributed in nature. It is a straight-chain alkyl carboxylic acid containing five carbon atoms. Due to the therapeutic value of valeric acid, it is used as a versatile nucleus in the pharmaceutical field. Valeric acid derivatives are associated with a broad spectrum of biological activities, like anticonvulsant, antiplatelet, antidiabetic, and plant growth activities. AIM: It has previously been revealed that peptide derivatives of carboxylic acids are accountable for enhanced antimicrobial activity. Therefore, it was hypothesized that coupling peptides with valeric acid would increase the antimicrobial properties of the target compounds. So, the objective of the present study was to synthesize peptide derivatives of 5-bromovaleric acid and evaluate their antibacterial and antifungal activities. METHODS: 5-bromovaleric acid was synthesized by the reaction of cyclopentanone and hydrogen peroxide in the presence of copper bromide and sodium bromide. Additionally, 5-bromovaleric acid was coupled with amino acid methyl esters, dipeptides, tripeptides, and tetrapeptides in the presence of dicyclohexylcarbodimide (DCC) and N-methylmorpholine (NMM) as a base under continuous stirring for 36 hours to produce its peptide derivatives. RESULTS: The results obtained showed that 5-bromovaleric acid possesses more potent antibacterial activity than N-terminal 5-bromovaleric acid conjugates of selected di-, tri, and tetra peptide Cterminal methyl esters against ciprofloxacin as a standard. The selected dipeptide and tripeptide Nterminal 5-bromovaleric acid-conjugated C-terminal methyl ester derivatives were more active than the selected tetrapeptide methyl ester analogue. Using fluconazole as a reference, the antifungal efficacy of 5-bromovaleric acid against C. albicans and A. niger declined as it was combined with C-terminal methyl esters of selected dipeptides, tripeptides, and tetrapeptides. CONCLUSION: The novel selected peptide derivatives had less antibacterial and antifungal action than the parent 5-bromovaleric acid. Antibacterial and antifungal investigations showed that 5- bromopentanoic acid peptide derivatives might impair antimicrobial efficacy. Further, attaching 5- bromopentanoic acid to di, tri, and tetra peptides did not boost their antibacterial potential.

6.
J Cancer Res Ther ; 20(3): 817-821, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023588

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a disease of the older population in developed countries where the incidence among the young is rising despite the decline in the overall incidence. Contrary to this, in India, which is a low-incidence country for CRCs, the incidence among all age groups including the young is rising. This study aimed at describing the clinico-demographic profile of young CRC cases and the epidemiological trend of the proportion of young cases from 2014 to 2021 in a tertiary cancer center in Eastern India. METHODS: This retrospective observational study was conducted at Department of Radiation Oncology, State Cancer Institute, IGIMS Patna, India a prominent tertiary cancer care center of Bihar. All histopathologically confirmed CRC cases in the 0-39 years age group were considered young and evaluated for the clinical, demographic profile as well as yearly trends in proportion out of total CRC cases. Microsoft Excel (2021) was used for statistical analysis. A P value of 0.05 was considered significant. RESULTS: Young colorectal (less than 40 years) patients constituted a third (n = 344, 33.4%) of total colorectal (n = 1028) cases. The median age among the young CRC cases was 30 years (range: 12 to 39 years). Rectum was the most common subsite noted (n = 255,74.1%) among this group of young patients. The most commonly encountered stage of the disease was III (n = 107, 31.1%) and chemotherapy was the most common treatment offered (n = 153, 44.5%). The proportion of young (0-39 years) CRC cases ranged between 29.4 and 37.4 (mean 33.5 ± 2.77, P value = 0.725) over the calendar years of the study period. CONCLUSION: The proportion of young (<40 years of age) cases out of total CRC cases in our study is higher than that in developed countries. However, the trends of this proportion have been consistent over the study period, i.e., from 2014 to 2021 without any significant change in our hospital-based cancer registry. Rectal cancer affected nearly three out of every four CRC patients in this age group. More advanced disease at presentation emphasizes the need for measures of screening, early diagnosis, and adequate infrastructure for treatment.


Asunto(s)
Neoplasias Colorrectales , Humanos , India/epidemiología , Estudios Retrospectivos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Masculino , Femenino , Adulto , Adulto Joven , Adolescente , Niño , Incidencia , Preescolar , Lactante , Recién Nacido , Factores de Edad
7.
Parasitol Res ; 123(7): 278, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023835

RESUMEN

Cutaneous leishmaniasis (CL) is often considered a 'great imitator' and is the most common form of leishmaniasis. The Leishmania species responsible for CL varies among countries, as these species exhibit specific distribution patterns. The increased mobility of people across countries has resulted in the imported incidences of leishmaniasis caused by non-endemic species of Leishmania. During 2023, we confirmed three CL cases caused by L. major from Kerala, India, and upon detailed investigation, these were identified to be imported from the Middle East and Kazakhstan regions. This is the first report of CL caused by L. major from Kerala. The lesion morphology, detection of anti-rK 39 antibody and Leishmania parasite DNA from the blood samples were the unique observations of these cases. Kerala, being an emerging endemic zone of visceral leishmaniasis (VL) and CL, the imported incidences of leishmaniasis by non-endemic species can pose a significant threat, potentially initiating new transmission cycles of leishmaniasis caused by non-endemic species.


Asunto(s)
Leishmania major , Leishmaniasis Cutánea , India/epidemiología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/diagnóstico , Humanos , Masculino , Leishmania major/aislamiento & purificación , Leishmania major/genética , Adulto , Femenino , Enfermedades Transmisibles Importadas/parasitología , Enfermedades Transmisibles Importadas/epidemiología , Persona de Mediana Edad , ADN Protozoario/genética , Anticuerpos Antiprotozoarios/sangre
8.
Cell Rep Med ; 5(7): 101640, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38959885

RESUMEN

CD8+ T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8+ T cells from 132 patients with seven human cancers. Our meta-single-cell analyses uncover a pan-cancer T cell dysfunction program that predicts clinical non-response to checkpoint blockade in melanoma and highlights CXCR6 as a pan-cancer marker of chronically activated T cells. Cxcr6 is trans-activated by AP-1 and repressed by TCF1. Using mouse models, we show that Cxcr6 deletion in CD8+ T cells increases apoptosis of PD1+TIM3+ cells, dampens CD28 signaling, and compromises tumor growth control. Our study uncovers a TCF1:CXCR6 axis that counterbalances PD1-mediated suppression of CD8+ cell responses and is essential for effective anti-tumor immunity.


Asunto(s)
Antígenos CD28 , Linfocitos T CD8-positivos , Factor Nuclear 1-alfa del Hepatocito , Receptores CXCR6 , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Animales , Humanos , Antígenos CD28/metabolismo , Antígenos CD28/genética , Antígenos CD28/inmunología , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Factor Nuclear 1-alfa del Hepatocito/genética , Ratones , Receptores CXCR6/metabolismo , Receptores CXCR6/genética , Neoplasias/inmunología , Neoplasias/genética , Neoplasias/patología , Análisis de la Célula Individual/métodos , Transducción de Señal , Microambiente Tumoral/inmunología , Ratones Endogámicos C57BL
9.
Indian J Microbiol ; 64(2): 318-327, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39011019

RESUMEN

In the current scenario of growing world population, limited cultivable land resources, plant diseases, and pandemics are some of the major factors responsible for declining global food security. Along with meeting the food demand, the maintenance of food quality is also required to ensure healthy consumption and marketing. In agricultural fields, pest infestations and bacterial diseases are common causes of crop damage, leading to massive yield losses. Conventionally, antibiotics and several pesticides have been used to manage and control these plant pathogens. However, the overuse of antibiotics and pesticides has led to the emergence of resistant strains of pathogenic bacteria. The bacteriophages are the natural predators of bacteria and are host-specific in their action. Therefore, the use of bacteriophages for the biocontrol of pathogenic bacteria is serving as a sustainable and green solution in crop protection and production. In this review, we have discussed the important plant pathogens and their impact on plant health and yield loss. Further, we have abridged the role of bacteriophages in the protection of crops from bacterial disease by discussing various greenhouse and field trials. Finally, we have discussed the impact of bacteriophages on the plant microbiome, phage resistance, and legal challenges in the registration and commercial production of bacteriophage-based biopesticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01204-x.

10.
Trials ; 25(1): 484, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014495

RESUMEN

BACKGROUND: High flow nasal cannula (HFNC) has been increasingly adopted in the past 2 decades as a mode of respiratory support for children hospitalized with bronchiolitis. The growing use of HFNC despite a paucity of high-quality data regarding the therapy's efficacy has led to concerns about overutilization. We developed an electronic health record (EHR) embedded, quality improvement (QI) oriented clinical trial to determine whether standardized management of HFNC weaning guided by clinical decision support (CDS) results in a reduction in the duration of HFNC compared to usual care for children with bronchiolitis. METHODS: The design and summary of the statistical analysis plan for the REspiratory SupporT for Efficient and cost-Effective Care (REST EEC; "rest easy") trial are presented. The investigators hypothesize that CDS-coupled, standardized HFNC weaning will reduce the duration of HFNC, the trial's primary endpoint, for children with bronchiolitis compared to usual care. Data supporting trial design and eventual analyses are collected from the EHR and other real world data sources using existing informatics infrastructure and QI data sources. The trial workflow, including randomization and deployment of the intervention, is embedded within the EHR of a large children's hospital using existing vendor features. Trial simulations indicate that by assuming a true hazard ratio effect size of 1.27, equivalent to a 6-h reduction in the median duration of HFNC, and enrolling a maximum of 350 children, there will be a > 0.75 probability of declaring superiority (interim analysis posterior probability of intervention effect > 0.99 or final analysis posterior probability of intervention effect > 0.9) and a > 0.85 probability of declaring superiority or the CDS intervention showing promise (final analysis posterior probability of intervention effect > 0.8). Iterative plan-do-study-act cycles are used to monitor the trial and provide targeted education to the workforce. DISCUSSION: Through incorporation of the trial into usual care workflows, relying on QI tools and resources to support trial conduct, and relying on Bayesian inference to determine whether the intervention is superior to usual care, REST EEC is a learning health system intervention that blends health system operations with active evidence generation to optimize the use of HFNC and associated patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05909566. Registered on June 18, 2023.


Asunto(s)
Teorema de Bayes , Bronquiolitis , Cánula , Sistemas de Apoyo a Decisiones Clínicas , Registros Electrónicos de Salud , Terapia por Inhalación de Oxígeno , Humanos , Bronquiolitis/terapia , Terapia por Inhalación de Oxígeno/métodos , Lactante , Resultado del Tratamiento , Ensayos Clínicos Pragmáticos como Asunto , Interpretación Estadística de Datos , Mejoramiento de la Calidad , Factores de Tiempo , Análisis Costo-Beneficio
11.
Cureus ; 16(5): e60569, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38894757

RESUMEN

BACKGROUND: Infected wounds pose a special challenge for management, with an increased risk of wound chronicity, systemic infection, and the emergence of antibiotic resistance. Silver nanoparticles have multimodal effects on bacteria clearance and wound healing. This study aimed to document the efficacy of a topical silver nanoparticle-based cream on bacteria clearance and wound healing in infected wounds compared to Mupirocin. METHODS: This open-label parallel randomized clinical trial allocated 86 participants with infected wounds (culture-positive) into Kadermin, silver nanoparticle-based cream arm (n=43) and Mupirocin arm (n=43) and documented the swab culture on day 5 and wound healing at day 28, along with periodic wound status using the Bates-Jensen Wound Assessment Tool. Patients received oral/systemic antibiotics and other medications for underlying diseases. The intention-to-treat principle was adopted for data analysis using the chi-square and Student t tests to document the differences between groups according to variable characteristics. RESULTS: All participants completed the follow-up. On day 5, wound bacteria clearance was observed in 86% and 65.1% of the participants in the Kadermin and Mupirocin arms, respectively (p=0.023). At day 28, complete wound healing was observed in 81.4% and 37.2% of the participants in the Kadermin and Mupirocin arms, respectively (p≤0.001). No local or systemic adverse event or local reaction was observed in any of the participants. CONCLUSION: Kadermin, the silver nanoparticle-based cream, has better efficacy in achieving faster wound bacteria clearance and healing in infected wounds compared to Mupirocin. This may have relevance for its use as an antibiotic-sparing agent in wound management.

12.
J Chem Phys ; 160(22)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38856063

RESUMEN

We performed high-level ab initio quantum chemical calculations, incorporating higher-order excitations, spin-orbit coupling (SOC), and the Gaunt interaction, to calculate the electron affinities (EAs) of alkaline earth (AE) metal atoms (Ca, Sr, Ba, and Ra), which are notably small. The coupled-cluster singles and doubles with perturbative triples [CCSD(T)] method is insufficient to accurately calculate the EAs of AE metal atoms. Higher-order excitations proved crucial, with the coupled-cluster singles, doubles, and triples with perturbative quadruples [CCSDT(2)Q] method effectively capturing dynamic electron correlation effects. The contributions of SOC (ΔESOs) to the EAs calculated using the multireference configuration interaction method with the Davidson correction, including SOC, positively enhance the EAs; however, these contributions are overestimated. The Dirac-Hartree-Fock (DHF)-CCSD(T) method addresses this overestimation and provides reasonable values for ΔESO (ΔESO-D). Employing additional sets of diffuse and core-valence correlation basis sets is critical for accurately calculating the EAs of AE metal atoms. The contributions of the Gaunt interaction (ΔEGaunt) to the EAs of AE metal atoms are negligible. Notably, the CCSDT(2)Q with the complete basis set limit + ΔESO-D + ΔEGaunt produced EA values for Ca, Sr, and Ba that closely aligned with experimental data and achieved accuracy exceeding the chemical accuracy. Based on our findings, the accurately proposed EA for Ra is 9.88 kJ/mol.

13.
Neurol Clin Pract ; 14(5): e200333, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38919932

RESUMEN

Background and Objectives: This study presents results from a survey of physicians performing electrodiagnostic studies to assess average volume. We also assessed how different factors (trainees, technologists, age of the physician, and case complexity) affected volume. Productivity is an important factor for physicians across practice settings. However, unlike evaluation and management services for neurologists, there are no published data for benchmarks of average volume of electrodiagnostic studies. Methods: A 34-question survey was designed collecting information on demographics, electrodiagnostic study volume, technologists, trainees, referrals, and case complexity. The anonymous survey was disseminated through a QR code or hyperlink to multiple online neurology, physical medicine and rehabilitation, electromyography, and neuromuscular forums. The primary outcome was EMG volume including number of EMGs per half-day and EMG volume per year. We conducted bivariate association analysis between primary outcomes and respondent characteristics using the Pearson χ2 test. Multivariable regression models determined factors associated with each of our outcome variables. Results: A total of 201 respondents initiated the survey. 71% were certified in adult neurology, 19.6% in physical medicine and rehabilitation, and 2.7% in pediatric neurology. 37.5% practiced in academic medicine. The remaining respondents were from private practice, group, solo, hospital employed, or other. 83% of respondents allotted a dedicated half-day to performing EMGs. The median number of EMGs scheduled during a half-day was within 3-4 (45%). 30% and 7% scheduled 5-6 or more than 7 patients per half-day, respectively. The median number of EMGs performed per year was within 251-500 (37%). Discussion: This national, cross-sectional survey evaluates average metrics of EMG volume. Our survey showed that the median number of EMGs annually lies between 251 and 500 studies (37%). In addition, for those respondents who allotted a dedicated half-day to performing EMGs, the median number of EMG studies scheduled per half-day lies between 3 and 4 studies (45%). In multivariate analysis, respondent characteristics of age of the physician (older than 45), working with nerve conduction technologists, and holding the position of EMG director were associated with increased EMG volume.

14.
Photochem Photobiol ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943225

RESUMEN

Elevated global pollution level is the prime reason that contributes to the onset of various harmful health diseases. The products of Biginelli reaction are enormously used in the pharmaceutical industry as they have antiviral, antibacterial, and calcium channel modulation abilities. This work reports a novel eosin Y sensitized boron graphitic carbon nitride (EY-Ben-g-C3N4) as a photocatalyst that efficiently produced 3,4-dihydropyrimidine-2-(1H)-one by the Biginelli reaction of benzaldehyde, urea, and methyl acetoacetate. The photocatalyst EY-Ben-g-C3N4 showed a successful generation of 3,4-dihydropyrimidine-2-(1H)-one (Biginelli product) in good yield via photocatalysis which is an eco-friendly method and has facile operational process. In addition to the production of Biginelli products, the photocatalyst also showed a remarkable NADH regeneration of 81.18%. The incorporation of g-C3N4 with boron helps increase the surface area and the incorporation of eosin Y which is an inexpensive and non-toxic dye, and in Ben-g-C3N4, enhanced the light-harvesting capacity of the photocatalyst. The production of 3,4-dihydropyrimidine-2-(1H)-one and NADH by the EY-Ben-g-C3N4 photocatalyst is attributed to the requisite band gap, high molar absorbance, low rate of charge recombination, and increased capacity of the photocatalyst to harvest solar light energy.

15.
Sci Rep ; 14(1): 13228, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853164

RESUMEN

Petroleum fuels are commonly used for automobiles. However, the continuous depletion and exhaust gas emission causes serious problems. So, there is a need for an alternative eco-friendly fuel. Biodiesel is a type of fuel manufactured through a process called transesterification, which involves converting vegetable oils into a usable form. The process parameters of the transesterification process were optimized using the Taguchi method to achieve maximum biodiesel yield. However, the main problem of biodiesel is its high cost which could be reduced by using low-cost feedstock. To address this challenge, biodiesel (BCFAD) is derived from coconut fatty acid distillate (CFAD), a by-product obtained from refining coconut oil. This work uses BCFAD and BCFAD with Alumina nanoparticles as fuels. Alumina nanoparticles in the mass fraction of 25 ppm, 50 ppm, and 100 ppm are dispersed in BCFAD. The investigation results reveal an increase of 6.5% in brake thermal efficiency for BCFAD with 100 ppm nanoparticles when compared to BCFAD. There is a reduction of 29.29% of hydrocarbon and 34% of Carbon monoxide emissions with BCFAD100 in comparison with diesel. However, there is a marginal increase in NOx emission with the increase in nanoparticles. The heat release rate and cylinder pressure of BCFAD100 are comparable to diesel fuel. It was concluded that the utilization of BCFAD with a nanoparticle dispersion of 100 ppm is suitable for direct use as fuel in diesel engines.

17.
Nat Aging ; 4(7): 949-968, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38918603

RESUMEN

Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data from humans and mice with metabolic dysfunction-associated liver disease, validated findings with functional studies in mice and applied the signature to transcriptomic data from other organs to determine whether aging-sensitive degenerative mechanisms are conserved. We discovered that the signature enriches in diseased livers in parallel with degeneration. It is also enriched in failing human hearts, diseased kidneys and pancreatic islets from individuals with diabetes. The signature includes genes that control ferroptosis. Aged mice develop more hepatocyte ferroptosis and liver degeneration than young mice when fed diets that induce metabolic stress. Inhibiting ferroptosis shifts the liver transcriptome of old mice toward that of young mice and reverses aging-exacerbated liver damage, identifying ferroptosis as a tractable, conserved mechanism for aging-related tissue degeneration.


Asunto(s)
Envejecimiento , Ferroptosis , Animales , Envejecimiento/metabolismo , Envejecimiento/patología , Ratones , Masculino , Humanos , Hepatocitos/metabolismo , Hepatocitos/patología , Hígado/metabolismo , Hígado/patología , Hígado Graso/metabolismo , Hígado Graso/patología , Transcriptoma , Estrés Fisiológico/fisiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
18.
Cell Rep ; 43(6): 114311, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38848214

RESUMEN

The lymphatic fluid is the conduit by which part of the tissue "omics" is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the lymph inflammatory and damage-associated molecular pattern signatures, microbiome-derived by-products, and immunomodulatory molecules, including metabolites of the gut-brain axis, mapped in the afferent mesenteric lymph. Our data point to the relevance of the lymphatic fluid to probe the tissue-specific antigenic and inflammatory load transported to the draining lymph node for immunosurveillance.


Asunto(s)
Antígenos , Inflamación , Ganglios Linfáticos , Linfa , Ratones Endogámicos C57BL , Animales , Ratones , Linfa/metabolismo , Linfa/inmunología , Inflamación/inmunología , Inflamación/patología , Inflamación/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Humanos , Antígenos/metabolismo , Antígenos/inmunología , Masculino , Femenino , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo
19.
J Oral Maxillofac Pathol ; 28(1): 37-41, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800434

RESUMEN

Background: Gutka chewing is the most common deleterious oral habit prevalent in the geographical distribution of the Indian subcontinent. Gutka leads to the production of numerous free radicals, which causes oxidative stress in regional oral tissues. Oxidative stress brings about the oxidation of guanine bases of DNA that generates 8-OHdG as its main byproduct. The presence of 8-OHdG can be evaluated not only in tissue but also in saliva, blood and urine. The availability of 8-OHdG in these samples is quite documented. In addition, a comparative assay of 8-ohdg DNA damage marker in multiple samples is yet to be done. Material and Methodology: A sample size of 60 was divided into two groups, i.e., gutka consumers without any lesion and gutka consumers with OSMF. Ten samples each of saliva, serum and urine were collected from these two groups and healthy controls. Samples were centrifuged at 1000 RPM at 2-8°C for 15-20 minutes. A volume of 1.5 ml resultant supernatant was pipetted out in labelled Eppendorf tubes and stored at -80°C. The ELISA test was performed to measure the concentration of 8-OHdG protein in different samples at 450 nm after adding stop solution in 96-well microplate. Results: 8-OHdG concentration was found to be highest in saliva followed by urine and serum. 8-OHdG concentration in serum was significantly less than that in saliva and urine (P-value <0.05). Intergroup difference in concentration of 8-OHdG of urine, saliva and serum was significant (P-value <0.05). Post hoc analysis revealed that concentration of 8-OHdG in saliva and urine was non-significantly different (P-value >0.05). Conclusion: Saliva appears to be the most appropriate sample type as compared to serum and urine for the evaluation of 8-OHdG in OSMF subjects.

20.
Microorganisms ; 12(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38792789

RESUMEN

Noncoding RNAs (ncRNAs) play key roles in the regulation of important pathways, including cellular growth, stress management, signaling, and biofilm formation. Sulfate-reducing bacteria (SRB) contribute to huge economic losses causing microbial-induced corrosion through biofilms on metal surfaces. To effectively combat the challenges posed by SRB, it is essential to understand their molecular mechanisms of biofilm formation. This study aimed to identify ncRNAs in the genome of a model SRB, Oleidesulfovibrio alaskensis G20 (OA G20). Three in silico approaches revealed genome-wide distribution of 37 ncRNAs excluding tRNAs in the OA G20. These ncRNAs belonged to 18 different Rfam families. This study identified riboswitches, sRNAs, RNP, and SRP. The analysis revealed that these ncRNAs could play key roles in the regulation of several pathways of biosynthesis and transport involved in biofilm formation by OA G20. Three sRNAs, Pseudomonas P10, Hammerhead type II, and sX4, which were found in OA G20, are rare and their roles have not been determined in SRB. These results suggest that applying various computational methods could enrich the results and lead to the discovery of additional novel ncRNAs, which could lead to understanding the "rules of life of OA G20" during biofilm formation.

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