Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 212
Filtrar
1.
Clin Ther ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38897838

RESUMEN

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

2.
J Periodontal Res ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808521

RESUMEN

AIM: Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery. METHODS: This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well. RESULTS: Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group. CONCLUSION: The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers.

3.
Nat Immunol ; 25(4): 598-606, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38565970

RESUMEN

The intricate relationship between immune dysregulation and neurodevelopmental disorders (NDDs) has been observed across the stages of both prenatal and postnatal development. In this Review, we provide a comprehensive overview of various maternal immune conditions, ranging from infections to chronic inflammatory conditions, that impact the neurodevelopment of the fetus during pregnancy. Furthermore, we examine the presence of immunological phenotypes, such as immune-related markers and coexisting immunological disorders, in individuals with NDDs. By delving into these findings, we shed light on the potential underlying mechanisms responsible for the high occurrence of immune dysregulation alongside NDDs. We also discuss current mouse models of NDDs and their contributions to our understanding of the immune mechanisms underlying these diseases. Additionally, we discuss how neuroimmune interactions contribute to shaping the manifestation of neurological phenotypes in individuals with NDDs while also exploring potential avenues for mitigating these effects.


Asunto(s)
Trastornos del Neurodesarrollo , Neuroinmunomodulación , Embarazo , Animales , Femenino , Ratones , Trastornos del Neurodesarrollo/genética , Modelos Animales de Enfermedad
4.
One Health ; 18: 100719, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38585666

RESUMEN

The winter of 2020-2021 in South Korea witnessed severe outbreaks of Highly Pathogenic Avian Influenza (HPAI) viruses, specifically multiple genotypes of the H5N8 subtype. These outbreaks prompted an extensive investigation into the genetic characteristics and evolutionary dynamics of these viruses. Under the auspices of the National Institute of Wildlife Disease Control and Prevention (NIWDC), we conducted a nationwide surveillance program, collecting 7588 specimens from diverse wild bird habitats. Influenza A viruses were isolated at a rate of 5.0%, with HPAI H5N8 viruses accounting for 38.5% of isolates, predominantly found in wild bird carcasses (97.3%). Genetic analysis revealed the emergence of novel HPAI genotypes due to genetic reassortment events. G1 and G2 viruses were separately introduced into Korea, with G1 viruses displaying dynamic behavior, resulting in diverse sub-genotypes (G1-1 to G1-5) and mainly isolated from clinical specimens. Conversely, the G2 virus, introduced later, became the dominant strain consistently isolated mainly from bird carcasses (88.9%). These findings underscore the emergence of numerous novel HPAI genotypes shaped by multiple reassortment events in high-density wintering grounds of migratory birds. These sites act as hotspots for genetic exchanges, significantly influencing avian ecology, including resident bird species, and contributing to HPAI H5N8 evolution. The genetic diversity and ongoing evolution of these viruses highlight the need for vigilant surveillance and adaptive control measures. Recognizing the potential spillover to human populations, a One Health approach is essential to mitigate the evolving threats posed by avian influenza.

5.
medRxiv ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38370801

RESUMEN

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8 + T cells, and the enhanced expression of T cell exhaustion markers, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-3 (Tim-3), in pregnant women. We identified additional evidence of immune dysfunction in severely and critically ill pregnant women, including a lack of expected elevation in regulatory T cell (Treg) levels, diminished interferon responses, and profound suppression of monocyte function. Consistent with earlier data, we found maternal obesity was also associated with altered immune responses to SARS-CoV-2 infection, including enhanced production of inflammatory cytokines by T cells. Certain gut bacterial species were altered in pregnancy and upon SARS-CoV-2 infection in pregnant individuals compared to non-pregnant women. Shifts in cytokine and chemokine levels were also identified in the sera of pregnant individuals, most notably a robust increase of interleukin-27 (IL-27), a cytokine known to drive T cell exhaustion, in the pregnant uninfected control group compared to all non-pregnant groups. IL-27 levels were also significantly higher in uninfected pregnant controls compared to pregnant SARS-CoV-2-infected individuals. Using two different preclinical mouse models of inflammation-induced fetal demise and respiratory influenza viral infection, we found that enhanced IL-27 protects developing fetuses from maternal inflammation but renders adult female mice vulnerable to viral infection. These combined findings from human and murine studies reveal nuanced pregnancy-associated immune responses, suggesting mechanisms underlying the increased susceptibility of pregnant individuals to viral respiratory infections.

6.
Emerg Microbes Infect ; 13(1): 2302854, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38189114

RESUMEN

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.


Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Animales , Humanos , Subtipo H5N1 del Virus de la Influenza A/genética , Hemaglutininas , Virulencia , Hurones , Pollos
7.
Arch Sex Behav ; 53(1): 77-90, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37950133

RESUMEN

In this qualitative study, we explored the challenges that transgender and gender non-confirming (TGNC) individuals face in South Korea. For this, we conducted in-depth interviews with 14 South Korean TGNC younger adults attending colleges or graduate schools and analyzed their data through consensus qualitative research. Analyses revealed that issues related to interpersonal relationships and medical transiting were major challenges perceived by participants. Four categories emerged in the domain of challenges in interpersonal relationships, including issues associated with family, romantic partner, coming out and outing, and transphobia and cisnormativity. In addition, two categories (i.e., medical difficulties and physical appearance-related distress) were included in the domain of challenges related to medical transition. Unique sources of stress for South Korean TGNC younger adults included high risk of being outed due to Korean resident registration numbers, dissatisfaction with bodily changes when transitioning, and misgendering caused by Korean's different honorific titles depending on gender.


Asunto(s)
Personas Transgénero , Transexualidad , Adulto , Humanos , Identidad de Género , Estigma Social , República de Corea
8.
J Control Release ; 364: 420-434, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37918486

RESUMEN

Endogenous stem cell-based in-situ tissue regeneration has recently gained considerable attention. In this study, we investigated the potential of a chemokine, SDF-1-mimic peptide (SMP), to promote endogenous stem cell-based in-situ wound healing. Our approach involved the development of a click crosslinked hyaluronic acid scaffold loaded with SMP (Cx-HA + SMP) to release SMP in a wound site. The Cx-HA scaffold maintained its structural integrity throughout the wound healing process and also captured endogenous stem cells. Gradual SMP release from the Cx-HA + SMP scaffold established a concentration gradient at the wound site. In animal wound experiments, Cx-HA + SMP exhibited faster wound contraction compared to Cx-HA + SDF-1. Additionally, Cx-HA + SMP resulted in approximately 1.2-1.6 times higher collagen formation compared to Cx-HA + SDF-1. SMP released from the Cx-HA + SMP scaffold promoted endogenous stem cell migration to the wound site 1.5 times more effectively than Cx-HA + SDF-1. Moreover, compared to Cx-HA + SDF-1, Cx-HA + SMP exhibited higher expression of CXCR4 and CD31, as well as the positive markers CD29 and CD44 for endogenous stem cells. The endogenous stem cells that migrated through Cx-HA + SMP regenerated into wound skin with minimal scar granule formation, similar to the normal tissue. In conclusion, SMP peptide offers greater convenience, while efficiently attracting migrating endogenous stem cells compared to the SDF protein. Our findings suggest that Cx-HA + SMP scaffolds hold promise as a strategy to enhance endogenous stem cell-based in-situ wound healing.


Asunto(s)
Ácido Hialurónico , Cicatrización de Heridas , Animales , Movimiento Celular , Células Madre/metabolismo , Quimiocina CXCL12
9.
Biomed Pharmacother ; 169: 115883, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37979373

RESUMEN

The stimulator of the interferon gene (STING) signaling pathway acts as a primary defense system against DNA pathogens. Because of the crucial role of STING in type I interferon (IFN) response and innate immunity, extensive research has been conducted to elucidate the roles of various effector molecules involved in STING-mediated signal transduction. However, despite the substantial contribution of microtubules to the immune system, the association between the STING signaling pathway and microtubules remains unclear. In this study, we revealed that the modulation of STING via microtubule-destabilizing agents (MDAs) specifically induced type I IFN responses rather than inflammatory responses in human monocytes. Co-treatment of MDAs with STING agonists induced the elevation of phospho-TANK-binding kinase 1 (TBK1), amplifying the innate immune response. However, during the deficiency of TBK1, the non-canonical signaling pathway through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) contributed to MDA-induced STING activation in type I IFN response which suggested the versatile regulation of MDA in STING-mediated immunity.


Asunto(s)
Interferón Tipo I , Monocitos , Humanos , Inmunidad Innata/fisiología , Interferón Tipo I/metabolismo , Proteínas de la Membrana/metabolismo , Monocitos/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/fisiología
10.
Cell Rep ; 42(9): 113077, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37676771

RESUMEN

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Humanos , SARS-CoV-2/genética , Hurones , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/química , Mutación/genética , Replicación Viral/genética
11.
PLoS One ; 18(9): e0291198, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37676879

RESUMEN

Extracellular vesicles (EVs) contain a variety of biomolecules and provide information about the cells that produce them. EVs from cancer cells found in urine can be used as biomarkers to detect cancer, enabling early diagnosis and treatment. The potential of alpha-2-macroglobulin (A2M) and clusterin (CLU) as novel diagnostic urinary EV (uEV) biomarkers for bladder cancer (BC) was demonstrated previously. To validate the diagnostic value of these proteins in uEVs in a large BC cohort, urine handling conditions before uEV isolation should be optimized during sample transportation from medical centers. In this study, we analyzed the uEV protein quantity, EV particle number, and uEV-A2M/CLU after urine storage at 20°C and 4°C for 0-6 days, each. A2M and CLU levels in uEVs were relatively stable when stored at 4°C for a maximum of three days and at 20°C for up to 24 h, with minimal impact on analysis results. Interestingly, pre-processing to remove debris and cells by centrifugation and filtration of urine did not show any beneficial effects on the preservation of protein biomarkers of uEVs during storage. Here, the importance of optimizing shipping conditions to minimize the impact of pre-analytical handling on the uEVs protein biomarkers was emphasized. These findings provide insights for the development of clinical protocols that use uEVs for diagnostic purposes.


Asunto(s)
Líquidos Corporales , Vesículas Extracelulares , alfa 2-Macroglobulinas Asociadas al Embarazo , Neoplasias de la Vejiga Urinaria , Humanos , Embarazo , Femenino , Neoplasias de la Vejiga Urinaria/diagnóstico , Vejiga Urinaria , Factores de Transcripción
12.
mBio ; 14(5): e0186823, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37712692

RESUMEN

IMPORTANCE: Dabie bandavirus (DBV) is an emerging tick-borne virus that causes severe fever with thrombocytopenia syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia. Thus, the development of vaccine to control this rapidly emerging virus is a high priority. In this study, we applied self-assembling ferritin (FT) nanoparticle to enhance the immunogenicity of DBV Gn head domain (GnH) as a vaccine target. Mice immunized with the GnH-FT nanoparticle vaccine induced potent antibody responses and cellular immunity. Immunized aged ferrets were fully protected from the lethal challenge of DBV. Our study describes the GnH-FT nanoparticle vaccine candidate that provides protective immunity against the emerging DBV infection.


Asunto(s)
Hurones , Síndrome de Trombocitopenia Febril Grave , Humanos , Animales , Ratones , Anciano , Nanovacunas , Modelos Animales de Enfermedad , Ferritinas
13.
Microorganisms ; 11(9)2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37764153

RESUMEN

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by Dabie bandavirus (SFTSV), is an emerging infectious disease first identified in China. Since its discovery, infections have spread throughout East Asian countries primarily through tick bites but also via transmission between animals and humans. The expanding range of ticks, the primary vectors for SFTSV, combined with migration patterns of tick-carrying birds, sets the stage for the global spread of this virus. SFTSV rapidly evolves due to continuous mutation and reassortment; currently, no approved vaccines or antiviral drugs are available. Thus, the threat this virus poses to global health is unmistakable. This review consolidates the most recent research on SFTSV, including its molecular characteristics, transmission pathways through ticks and other animals, as well as the progress in antiviral drug and vaccine development, encompassing animal models and clinical trials.

14.
Front Plant Sci ; 14: 1192235, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37636096

RESUMEN

Metabolomics refers to the technology for the comprehensive analysis of metabolites and low-molecular-weight compounds in a biological system, such as cells or tissues. Metabolites play an important role in biological phenomena through their direct involvement in the regulation of physiological mechanisms, such as maintaining cell homeostasis or signal transmission through protein-protein interactions. The current review aims provide a framework for how the integrated analysis of metabolites, their functional actions and inherent biological information can be used to understand biological phenomena related to the regulation of metabolites and how this information can be applied to safety assessments of crops created using biotechnology. Advancement in technology and analytical instrumentation have led new ways to examine the convergence between biology and chemistry, which has yielded a deeper understanding of complex biological phenomena. Metabolomics can be utilized and applied to safety assessments of biotechnology products through a systematic approach using metabolite-level data processing algorithms, statistical techniques, and database development. The integration of metabolomics data with sequencing data is a key step towards improving additional phenotypical evidence to elucidate the degree of environmental affects for variants found in genome associated with metabolic processes. Moreover, information analysis technology such as big data, machine learning, and IT investment must be introduced to establish a system for data extraction, selection, and metabolomic data analysis for the interpretation of biological implications of biotechnology innovations. This review outlines the integrity of metabolomics assessments in determining the consequences of genetic engineering and biotechnology in plants.

15.
PLoS Biol ; 21(8): e3002252, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37594983

RESUMEN

It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions.


Asunto(s)
Adiposidad , Proteína Relacionada con Agouti , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Obesidad , Animales , Ratones , Proteína Relacionada con Agouti/genética , Peso Corporal , Ratones Noqueados , Neuronas , Péptidos , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/genética
16.
Biomed Pharmacother ; 166: 115312, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37567072

RESUMEN

Histone deacetylases (HDACs) are key epigenetic regulators and classified into four subtypes. Despite the various roles of each HDAC isoform, the lack of selective HDAC inhibitors has limited the elucidation of their roles in biological systems. HDAC11, the sole class-IV HDAC, is highly expressed in the brain, however, the role of HDAC11 in microglia is not fully understood. Based on the modification of MC1568, we developed a novel HDAC inhibitor, 5. Interestingly, 5 suppresses lipopolysaccharide-induced microglial activation by the initiation of autophagy and subsequent inhibition of nitric oxide production. Furthermore, we demonstrated that 5 significantly alleviates depression-like behavior by inhibiting microglial activation in mouse brain. Our discovery reveals that specific pharmacological regulation of HDAC11 induces autophagy and reactive nitrogen species balance in microglia for the first time, which makes HDAC11 a new therapeutic target for depressive disorder.


Asunto(s)
Depresión , Inhibidores de Histona Desacetilasas , Microglía , Animales , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Depresión/genética , Depresión/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo
17.
bioRxiv ; 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37503275

RESUMEN

Dabie Bandavirus (DBV), previously known as Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (>4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens for inducing both neutralizing antibody (NAb)- and T cell-mediated immunity and, thereby, protection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present DBV Gn head region (GnH) for enhanced immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection.

18.
Bioorg Med Chem Lett ; 92: 129408, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37429500

RESUMEN

A series of thalidomide analogues, where the fused benzene ring in the phthalimide moiety was converted into two separated diphenyl rings in maleimide moiety and N-aminoglutarimide moiety was replaced by substituted phenyl moiety, were synthesized and evaluated for their NO inhibitory activities on BV2 cells stimulated with lipopolysaccharide (LPS). Among the synthesized compounds, the dimethylaminophenyl analogue 1s (IC50 = 7.1 µM) showed significantly higher inhibitory activity than the glutarimide analogue 1a (IC50 > 50 µM) and suppressed NO production dose-dependently without cytotoxicity. In addition, 1s inhibited the production of pro-inflammatory cytokines and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by blocking nuclear factor-kappa B (NF-κB) and p38 MAPK pathways. These results demonstrated that 1s showed good anti-inflammatory activity and could become a leading compound for the treatment of neuroinflammatory diseases.


Asunto(s)
Lipopolisacáridos , Pirroles , Lipopolisacáridos/farmacología , Pirroles/metabolismo , Antiinflamatorios , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Microglía/metabolismo , Ciclooxigenasa 2/metabolismo
19.
Healthcare (Basel) ; 11(11)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37297736

RESUMEN

(1) Background: This study aimed to identify factors associated with hypertension control among older adults with hypertension based on their socio-demographic and health characteristics. (2) Methods: The sample consisted of a total of 1824 with hypertension and was obtained from the Eighth Korean National Health and Nutrition Examination Survey (VIII-1, VIII-2). (3) Results: As the factors associated with hypertension control among older men, 65-74 years old (OR = 1.76, CI = 1.04-2.96), a lower education level (OR = 2.23, CI = 1.17-4.28), with obesity (OR = 2.05, CI = 1.13-2.05), and under-treatment of hypertension (OR = 22.07, CI = 6.54-7.45) increased the likelihood of rating hypertension control. As the factors associated with hypertension control among older women, trying to weight maintain (OR = 1.70, CI = 1.01-2.85) and under-treatment of hypertension (OR = 12.16, CI = 3.65-40.46) increased the likelihood of rating hypertension control. (4) Conclusion: The factor affecting the control of hypertension differed between the two genders. To improve the control of hypertension, the guidelines for treatment interventions should be gender-specific for the early elderly. There is a need to increase control of hypertension by having health-related behavioral modifications such as reducing obesity for older men and trying weight maintenance for older women.

20.
Anticancer Res ; 43(7): 3047-3056, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37351981

RESUMEN

BACKGROUND/AIM: The toxic side effects of therapies against breast cancer can affect the quality of life of patients, necessitating the use of naturally-derived therapeutics. Here, we investigated the effects of Dendropanax morbiferus H. Lév. leaf (DPL) extract on breast cancer cells in vitro and in vivo to assess its anticancer potential. MATERIALS AND METHODS: MDA-MB-231 breast cancer cells were treated with DPL, and the in vitro effect of DPL on the cells was evaluated through an MTT assay, DAPI staining, annexin V/propidium iodide double staining, and western blotting. The in vivo effects of DPL were measured through the MDA-MB-231 tumor xenograft mouse model. A TUNEL assay and immunohistochemistry were used to determine the extent of apoptosis and p-p38 expression in tumor tissues, respectively. RESULTS: DPL treatment significantly suppressed cell viability in a concentration-dependent manner. Furthermore, DPL treatment resulted in increased apoptotic body formation, apoptosis rate, cleaved poly (ADP-ribose) polymerase and B-cell lymphoma 2 (Bcl-2)-associated X protein levels, phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins, and decreased Bcl-2 levels. In addition, the antitumor effect in vivo was confirmed through the xenograft model, where decreased tumor volume and weight following DPL administration were observed. Further, apoptosis and increased p-p38 levels in tumor tissues were observed, and no pathological abnormalities were found in the liver or kidney. CONCLUSION: DPL inhibits proliferation through MAPK-mediated apoptosis in breast cancer cells and tumors, suggesting the potential of DPL as a natural therapeutic agent for breast cancer.


Asunto(s)
Neoplasias de la Mama , Proteínas Quinasas Activadas por Mitógenos , Humanos , Animales , Ratones , Femenino , Calidad de Vida , Proliferación Celular , Neoplasias de la Mama/patología , Apoptosis , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2 , Línea Celular Tumoral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...