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1.
Food Sci Biotechnol ; 33(7): 1615-1621, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623421

RESUMO

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.

2.
Int Immunopharmacol ; 132: 111937, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569427

RESUMO

Tuberculosis (TB) treatment requires a long therapeutic duration and induces adverse effects such as hepatotoxicity, causing discontinuation of treatment. Reduced adherence to TB medications elevates the risk of recurrence and the development of drug resistance. Additionally, severe cavitary TB with a high burden of Mycobacterium tuberculosis (Mtb) and inflammation-mediated tissue damage may need an extended treatment duration, resulting in a higher tendency of drug-induced toxicity. We previously reported that the administration of Lactobacillus sakei CVL-001 (L. sakei CVL-001) regulates inflammation and improves mucosal barrier function in a murine colitis model. Since accumulating evidence has reported the functional roles of probiotics in drug-induced liver injury and pulmonary inflammation, we employed a parabiotic form of the L. sakei CVL-001 to investigate whether this supplement may provide beneficial effects on the reduction in drug-induced liver damage and pulmonary inflammation during chemotherapy. Intriguingly, L. sakei CVL-001 administration slightly reduced Mtb burden without affecting lung inflammation and weight loss in both Mtb-resistant and -susceptible mice. Moreover, L. sakei CVL-001 decreased T cell-mediated inflammatory responses and increased regulatory T cells along with an elevated antigen-specific IL-10 production, suggesting that this parabiotic may restrain excessive inflammation during antibiotic treatment. Furthermore, the parabiotic intervention significantly reduced levels of alanine aminotransferase, an indicator of hepatotoxicity, and cell death in liver tissues. Collectively, our data suggest that L. sakei CVL-001 administration has the potential to be an adjunctive therapy by reducing pulmonary inflammation and liver damage during anti-TB drug treatment and may benefit adherence to TB medication in lengthy treatment.

3.
Small ; : e2400046, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441356

RESUMO

The development of cost-effective and high-performance oxygen evolution reaction (OER) catalysts is a significant challenge. This study presents the synthesis of binder-free NiFe@NiFe layered double hydroxide (NNF) via one-pot electrodeposition on carbon paper and Ni foam at high current densities. The presence of Ni sulfate residues on the prepared NNF is also investigated. The findings indicate that Ni sulfate significantly improves OER performance and durability. The sulfate content can be controlled by varying the method and duration of washing. NNF prepared through dipping (NNF-D) exhibits outstanding OER activity with a low overpotential of 241 mV, which is 25 mV lower than that of NNF washed for 60 s (NNF-W-60 s) at 10 mA cm-2 in 1 m KOH. Furthermore, density functional theory analyses indicate that the Ni sulfate residue helps modify the electronic structure, thereby optimizing the binding strength of *OOH. This synthetic strategy is expected to inspire the development of next-generation catalysts utilizing various adsorbates.

4.
J Clin Invest ; 134(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426494

RESUMO

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.


Assuntos
Artrite , Proteína Amiloide A Sérica , Animais , Camundongos , Artrite/metabolismo , Inflamação/patologia , Fígado/metabolismo , Ativação de Macrófagos , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fatores de Transcrição/metabolismo
5.
Sci Rep ; 14(1): 7309, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538678

RESUMO

Phase angle (PhA) is an indicator of cellular health and is positively associated with overall physical activity (PA). However, varied associations between different intensities of PA and PhA by body segment in older populations remain unexplored. We investigated the associations between overall and different intensities of PA and upper-, lower-, and whole-body PhA in older adults. Overall exposure to light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity physical activity (VPA) was assessed using a triaxial accelerometer (GT3X + , ActiGraph). The outcome variables were upper-, lower-, and whole-body PhA measured using bioelectrical impedance analysis (MC-780MA, TANITA). Multiple linear regression helped examine the associations between the exposure and outcome variables after adjusting for age, gender, body mass index, and accelerometer wear time. A cross-sectional analysis involved 166 community-dwelling older participants (mean age = 72.1 ± 5.5 years; 78.3% women). Overall PA was associated with larger upper- (B: 0.057, 95% confidence interval [CI] 0.018-0.095) and whole-body PhA (B: 0.044, 95% CI 0.006-0.081). LPA was associated with larger upper-body PhA (B: 0.059, 95% CI 0.017-0.101), and MPA was associated with larger lower- (B: 0.273, 95% CI 0.128-0.419) and whole-body PhA (B: 0.141, 95% CI 0.002-0.280). VPA and PhA were not associated. Future interventions targeting PhA in older adults should consider the differential impact of PA intensity on various body segments of the PhA.


Assuntos
Acelerometria , Exercício Físico , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Índice de Massa Corporal , Análise Multivariada
6.
World J Clin Cases ; 12(3): 517-524, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322465

RESUMO

BACKGROUND: Studies on varicose veins have focused its effects on physical function; however, whether nonsurgical treatments alter muscle oxygenation or physical function remains unclear. Moreover, the differences in such functions between individuals with varicose veins and healthy individuals remain unclear. AIM: To investigate changes in physical function and the quality of life (QOL) following nonsurgical treatment of patients with varicose veins and determine the changes in their muscle oxygenation during activity. METHODS: We enrolled 37 participants (those with varicose veins, n = 17; healthy individuals, n = 20). We performed the following measurements pre- and post-nonsurgical treatment in the varicose vein patients and healthy individuals: Calf muscle oxygenation during the two-minute step test, open eyes one-leg stance, 30 s sit-to-stand test, visual analog scale (VAS) for pain, Pittsburgh sleep quality index, physical activity assessment, and QOL assessment. RESULTS: Varicose veins patients and healthy individuals differ in most variables (physical function, sleep quality, and QOL). Varicose veins patients showed significant differences between pre- and post-nonsurgical treatment- results in the 30 sit-to-stand test [14.41 (2.45) to 16.35 (4.11), P = 0.018), two-minute step test [162.29 (25.98) to 170.65 (23.80), P = 0.037], VAS for pain [5.35 (1.90) to 3.88 (1.73), P = 0.004], and QOL [39.34 (19.98) to 26.69 (17.02), P = 0.005]; however, no significant difference was observed for muscle oxygenation. CONCLUSION: Nonsurgical treatment improved lower extremity function and QOL in varicose veins patients, bringing their condition close to that of healthy individuals. Future studies should include patients with severe varicose veins requiring surgery to confirm our findings.

7.
Nat Commun ; 15(1): 46, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167804

RESUMO

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.


Assuntos
Longevidade , Receptor 5 Toll-Like , Animais , Camundongos , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidade/genética , Pulmão/metabolismo
8.
Microorganisms ; 12(1)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38258014

RESUMO

Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of Lactobacillus kunkeei culture supernatant (CSK), isolated from Apis mellifera Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control H2O2-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove H2O2-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.

9.
J Environ Sci (China) ; 138: 350-372, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135402

RESUMO

Petroleum contamination is considered as a major risk to the health of humans and environment. Biochars as low-cost and eco-friendly carbon materials, have been widely used for the removal of petroleum hydrocarbon in the environment. The purpose of this paper is to review the performance, mechanisms, and potential environmental toxicity of biochar, modified biochar and its integration use with other materials in petroleum contaminated soil and water. Specifically, the use of biochar in oil-contaminated water and soil as well as the factors that could influence the removal ability of biochar were systematically evaluated. In addition, the modification and integrated use of biochar for improving the removal efficiency were summarized from the aspects of sorption, biodegradation, chemical degradation, and reusability. Moreover, the functional impacts and associated ecotoxicity of pristine and modified biochars in various environments were demonstrated. Finally, some shortcoming of current approaches, and future research needs were provided for the future direction and challenges of modified biochar research. Overall, this paper gain insight into biochar application in petroleum remediation from the perspectives of performance enhancement and environmental sustainability.


Assuntos
Petróleo , Poluentes do Solo , Humanos , Petróleo/metabolismo , Água , Poluentes do Solo/análise , Hidrocarbonetos , Biodegradação Ambiental , Solo , Carvão Vegetal , Microbiologia do Solo
10.
Nutrients ; 15(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068826

RESUMO

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.


Assuntos
Doenças Ósseas Metabólicas , Reabsorção Óssea , Osteoporose , Feminino , Animais , Camundongos , Osteoclastos , Reabsorção Óssea/tratamento farmacológico , Doenças Ósseas Metabólicas/metabolismo , Osteoporose/tratamento farmacológico , Ligante RANK/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Diferenciação Celular , Osteogênese
11.
JMIR Ment Health ; 10: e48912, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878378

RESUMO

BACKGROUND: Given the increasing incidence of early-onset Alzheimer disease, strategies for early diagnosis and swift treatment interventions are crucial for mitigating cognitive problems in women and middle-aged individuals who face a high risk of cognitive impairment. OBJECTIVE: This study aimed to assess the effectiveness of individual cognitive training programs based on virtual reality (VR), a nonpharmacological intervention, on cognitive function and depression in middle-aged women at risk of cognitive impairment. It used VR technology, which has recently been recognized as a promising tool. METHODS: We administered a VR-based cognitive training program for 30 minutes daily, twice a week, for 12 weeks (24 sessions). This study included middle-aged women residing in older adults' welfare facilities in G-gu, Busan, from May to August 2021. A total of 60 participants were randomly divided into the training (n=30) and control (n=30) groups. Cognitive and depressive functions were assessed using the Korean versions of the Montreal Cognitive Assessment (K-MoCA), Digit Span Test (DST), Korean-Color Word Stroop Test (K-CWST), and Short Form of the Geriatric Depression Scale (SGDS-K) before the intervention. The training group underwent a VR-based cognitive training program, whereas the control group was educated to maintain regular daily activities. The same assessments were performed 12 weeks after treatment. RESULTS: A comparison of the mean scores before and after K-MoCA in the training group revealed a significant increase from 24.87 (SD 2.62) to 27.50 (SD 1.70; P<.01), indicating substantial cognitive improvement. Similarly, the mean DST forward scores increased significantly from 6.97 (SD 1.10) to 7.90 (SD 1.18; P<.01), suggesting enhanced short-term auditory memory and attention. The mean DST backward scores also showed a significant improvement from 4.10 (SD 0.71) to 4.77 (SD 1.2; P=.01). Notably, the mean SGDS-K scores decreased significantly from 3.97 (SD 2.51) to 2.13 (SD 1.87; P<.01), indicating a reduction in depression within the training group. CONCLUSIONS: The VR-based cognitive training programs significantly enhanced cognitive function and reduced depression in middle-aged women. Consequently, these programs are considered beneficial nonpharmacological cognitive training interventions for middle-aged women at high risk of cognitive impairment. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000049752; https://tinyurl.com/z5du989z.

12.
Emerg Med Int ; 2023: 5162050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881258

RESUMO

The base deficit (B), international normalized ratio (I), and Glasgow coma scale (GCS) (BIG) score is useful in predicting mortality in pediatric trauma patients; however, studies on the use of BIG score in adult patients with trauma are sparse. In addition, studies on the correlation between the BIG score and massive transfusion (MT) have not yet been conducted. This study aimed to evaluate the predictive value of BIG score for mortality and the need for MT in adult trauma patients. This retrospective study used data collected between 2016 and 2020 at our hospital's trauma center and registry. The predictive value of BIG score was compared with that of the Injury Severity Score (ISS) and Revised Trauma Score (RTS). Logistic regression analysis was carried out to assess whether BIG score was an independent risk factor. Receiver operating characteristic (ROC) curve analysis was performed, and predictive values were evaluated by measuring the area under the ROC curve (AUROC). In total, 5,605 patients were included in this study. In logistic regression analysis, BIG score was independently associated with in-hospital mortality (odds ratio (OR): 1.1859; 95% confidence interval (CI): 1.1636-1.2086) and MT (OR: 1.0802; 95% CI: 1.0609-1.0999). The AUROCs of BIG score for in-hospital mortality and MT were 0.852 (0.842-0.861) and 0.848 (0.838-0.857), respectively. Contrastingly, the AUROCs of ISS and RTS for in-hospital mortality were 0.795 (0.784-0.805) and 0.859 (0.850-0.868), respectively. Moreover, AUROCs of ISS and RTS for MT were 0.812 (0.802-0.822) and 0.838 (0.828-0.848), respectively. The predictive value of BIG score for mortality and MT was significantly higher than that of the ISS. The BIG score also showed a better AUROC for predicting in-hospital mortality compared with RTS. In conclusion, the BIG score is a useful indicator for predicting mortality and the need for MT in adult trauma patients.

13.
Environ Sci Pollut Res Int ; 30(55): 117143-117164, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37863853

RESUMO

Safe drinking water sources are crucial for human health. Consequently, water quality management, including continuous monitoring of water quality and algae at sources, is critical to ensure the availability of safe water for local residents. This study aimed to construct statistical prediction models considering probability distributions relevant to cyanophyte cell counts and compare their prediction performance. In this study, water quality parameters at Juam Lake and Tamjin Lake, representative water sources in the Yeongsan and Seomjin rivers, South Korea, were investigated. We used a water quality monitoring network, algae alert system, and hydraulic and hydrological data measured every 7 days from January 2017 to December 2022 from the Water Environment Information System of the National Institute of Environmental Research. Using data for 2017-2021 as a training set and data for 2022 as a test set, the performances of seven models were compared for predicting cyanophyte cell counts. Environmental factors associated with algae in water sources were observed based on the monitoring data, and a prediction model appropriate for the cyanophyte distribution was generated, which also included the risk of toxicity. The extreme gradient boosting with the random forest model had the best predictive performance for cyanophyte cell counts. The study results are expected to facilitate water quality management in various water systems, including water sources.


Assuntos
Rios , Qualidade da Água , Humanos , República da Coreia , Modelos Estatísticos , Lagos , Monitoramento Ambiental/métodos
14.
J Med Chem ; 66(20): 14263-14277, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37796116

RESUMO

Thiopeptides exhibit potent antimicrobial activity against Gram-positive pathogens by inhibiting bacterial protein synthesis. Micrococcins are among the structurally simpler thiopeptides, but they have not been exploited in detail. This research involved a computational simulation of micrococcin P2 (MP2) docking in parallel with the structure-activity relationship (SAR) studied. The incorporation of particular nitrogen heterocycles in the side chain of MP2 enhances the antimicrobial activity. Micrococcin analogues 6c and 6d thus proved to be more effective against impetigo and C. difficile infection (CDI), respectively, as compared to current first-line treatments. Compound 6c also showed a shorter treatment period than that of a first-line treatment for impetigo. This may be attributed to its ability to downregulate pro-inflammatory cytokines. Compound 6d had no observed recurrence for C. difficile and exerted a minimal impact on the beneficial gut microbiome. Their pharmacokinetic properties and low toxicity profile make these compounds ideal candidates for the treatment of impetigo and CDI and validate their involvement in preclinical development.


Assuntos
Clostridioides difficile , Impetigo , Humanos , Antibacterianos/farmacologia , Antibacterianos/química
15.
Front Public Health ; 11: 1241170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808987

RESUMO

Objective: Regarding the circadian rhythm regulating an individual's response to external stimulation, it remains unclear whether older adults engaged in physical activity at different times of day may be differently related to depression symptoms. Thus, this study aimed to investigate the association between overall and timing-specific physical activity and depressive symptoms in older Taiwanese adults. Methods: This cross-sectional study was conducted at a medical center in Taipei City, Taiwan, between September 2020 and December 2021. The participants were community-dwelling older adults aged ≥65 who could walk independently and were not at high risk of cognitive dysfunction. Physical activity was measured using a triaxial accelerometer (GT3X+, ActiGraph) and categorized into timing-specific periods (morning: 06:01-12:00; afternoon: 12:01-18:00; evening: 18:01-24:00) as well as overall physical activity, which included both light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). A 15-item Geriatric Depression Scale was utilized to assess and measure depressive symptoms. Multivariate linear regression models were estimated for data analysis. Results: A total of 180 older adults (55.0% female; 80.5 ± 7.1 years old; 18.3% at risk of depression) were included. On average, the participants spent 237.3 (± 85.7) minutes in LPA per day and 12.8 (± 17.0) minutes in MVPA per day. The results showed that overall MVPA engagement was associated with lower depressive-symptom scores [B = -1.357, 95% CI (-2.561, -0.153)] in older adults. However, no significant associations were observed between overall LPA, timing-specific MVPA and LPA, and depression in older adults. Conclusion: To prevent depression in older adults, it is advisable to accumulate a higher amount of MVPA throughout the entire day rather than engage in LPA. Further studies employing a prospective design are necessary to validate and strengthen our findings.


Assuntos
Disfunção Cognitiva , Depressão , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Transversais , Depressão/epidemiologia , Depressão/diagnóstico , Exercício Físico/fisiologia , Modelos Lineares
16.
Front Immunol ; 14: 1207121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457695

RESUMO

Introduction: Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a clinically significant global pathogen in the last decade. However, the host immune responses of the macrophages during hvKp infection are largely unknown. In the present study, we aimed to compare the cytotoxic effects of hvKp and classical K. pneumoniae (cKp) in murine macrophages. Results: We found that the activation of caspase-1 -dependent pyroptosis was higher in cKp-infected macrophages compared with that in hvKp-infected macrophages. In Caspase-1 deficiency macrophages, pyroptosis diminished during infection. Both hvKp and cKp strains led to nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome formation and lysosomal cathepsin B activation, thus resulting in pyroptosis. Compared with the cKp strain, the hvKp strain inhibited these phenomena in murine macrophages. Conclusion: HvKp infection resulted in different levels of pyroptosis via the activation of cathepsin B-NLRP3-caspase-1 in murine macrophages. Therefore, the manipulation of pyroptotic cell death is a potential target for host response during hvKp infection in macrophages.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Animais , Camundongos , Virulência , Piroptose , Catepsina B/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Macrófagos , Caspases
17.
Microorganisms ; 11(5)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37317332

RESUMO

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

18.
Diabetes Metab Syndr Obes ; 16: 1357-1366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37193576

RESUMO

Purpose: Research on whether wearable device interventions can effectively prevent metabolic syndrome remains insufficient. This study aimed to evaluate the effect of feedback on clinical indicators in patients with metabolic syndrome on activities measured using wearable devices, such as smartphone apps. Methods: Patients with metabolic syndrome were recruited and prescribed to live for 12 weeks using a wrist-wearable device (B.BAND, B Life Inc., Korea). A block randomization method was used to distribute participants between the intervention (n=35) and control groups (n=32). In the intervention group, an experienced study coordinator provided feedback on physical activity to individuals through telephonic counseling every other week. Results: The mean number of steps in the control group was 8892.86 (4473.53), and those in the intervention group was 10,129.31 (4224.11). After 12 weeks, metabolic syndrome was resolved. Notably, there were statistically significant differences in the metabolic composition among the participants who completed the intervention. The mean number of metabolic disorder components per person remained at 3 in the control group, and decreased from 4 to 3 in the intervention group. Additionally, waist circumference, systolic and diastolic blood pressure, and triglyceride levels were significantly reduced, while HDL-cholesterol levels were significantly increased in the intervention group. Conclusion: Overall, 12 weeks of telephonic counseling intervention using wearable device-based physical activity confirmation improved the damaged metabolic components of patients with metabolic syndrome. Telephonic intervention can help increase physical activity and reduce waist circumference, which is a typical clinical indicator of metabolic syndrome.

19.
Psychiatry Investig ; 20(5): 445-451, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37253470

RESUMO

OBJECTIVE: It is necessary to identify the mental health types of young women considering the importance of the mental health during the peripartum period. This study aimed to classify the mental health types in a community sample of young women with pre-pregnancy, pregnancy, or the postpartum period. METHODS: A total of 293 young women during pre-pregnancy, pregnancy, or the postpartum period were included in this study. The clinical characteristics of depression, anxiety, perceived stress, and quality of life were assessed. The clinical characteristics of the subject were classified by cluster analysis and compared by analysis of variance. RESULTS: From the cluster analysis, the subjects were classified into three groups. Cluster 1 showed significantly lower depression and anxiety and higher quality of life than those of cluster 2 and 3. Cluster 2 demonstrated significantly higher depression and anxiety and lower quality of life than those of cluster 3 and 1. Cluster 3 represented the intermediate levels between cluster 2 and 1. CONCLUSION: This study suggested that young women during pre-pregnancy, pregnancy, or the postpartum period might be in a good mental health group, a high-risk group requiring active monitoring, or a group in need of treatment. By monitoring mental health, the groups with high risk or requiring treatment could be discovered and proper management for prevention or improvement of mental health and quality of life can be provided.

20.
Mol Biol Rep ; 50(7): 5807-5816, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37219665

RESUMO

BACKGROUND: Eukaryotic initiation factor 5A hypusine (eIF5AHyp) stimulates the translation of proline repeat motifs. Salt inducible kinase 2 (SIK2) containing a proline repeat motif is overexpressed in ovarian cancers, in which it promotes cell proliferation, migration, and invasion. METHODS AND RESULTS: Western blotting and dual luciferase analyses showed that depletion of eIF5AHyp by GC7 or eIF5A-targeting siRNA downregulated SIK2 level and decreased luciferase activity in cells transfected with a luciferase-based reporter construct containing consecutive proline residues, whereas the activity of the mutant control reporter construct (replacing P825L, P828H, and P831Q) did not change. According to the MTT assay, GC7, which has a potential antiproliferative effect, reduced the viability of several ovarian cancer cell lines by 20-35% at high concentrations (ES2 > CAOV-3 > OVCAR-3 > TOV-112D) but not at low concentrations. In a pull-down assay, we identified eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP1 (p4E-BP1) phosphorylated at Ser 65 as downstream binding partners of SIK2, and we validated that the level of p4E-BP1(Ser 65) was downregulated by SIK2-targeting siRNA. Conversely, in ES2 cells overexpressing SIK2, the p4E-BP1(Ser 65) level was increased but decreased in the presence of GC7 or eIF5A-targeting siRNA. Finally, the migration, clonogenicity, and viability of ES2 ovarian cancer cells were reduced by GC7 treatment as well as by siRNA for eIF5A gene silencing and siRNA for SIK2 and 4E-BP1 gene silencing. Conversely, those activities were increased in cells overexpressing SIK2 or 4E-BP1 and decreased again in the presence of GC7. CONCLUSION: The depletion of eIF5AHyp by GC7 or eIF5A-targeting siRNA attenuated activation of the SIK2-p4EBP1 pathway. In that way, eIF5AHyp depletion reduces the migration, clonogenicity, and viability of ES2 ovarian cancer cells.


Assuntos
Apoptose , Neoplasias Ovarianas , Feminino , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Ovarianas/genética , Fatores de Iniciação de Peptídeos/genética , RNA Interferente Pequeno/genética
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