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1.
Food Res Int ; 194: 114907, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232532

RESUMO

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.


Assuntos
Frutas , Doenças Metabólicas , Phyllanthus emblica , Extratos Vegetais , Aldeído Pirúvico , Phyllanthus emblica/química , Aldeído Pirúvico/metabolismo , Humanos , Extratos Vegetais/farmacologia , Doenças Metabólicas/prevenção & controle , Frutas/química , Produtos Finais de Glicação Avançada/metabolismo , Animais
2.
Arch Microbiol ; 206(10): 401, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261350

RESUMO

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions.


Assuntos
Proteínas de Bactérias , Infecções Estafilocócicas , Staphylococcus aureus , Testosterona , Masculino , Testosterona/farmacologia , Testosterona/metabolismo , Animais , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Virulência , Infecções Estafilocócicas/microbiologia , Transativadores/genética , Transativadores/metabolismo , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum , Simulação de Acoplamento Molecular , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Abscesso/microbiologia , Hemólise , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/genética
3.
J Telemed Telecare ; : 1357633X241273032, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39295471

RESUMO

BACKGROUND: Mobile applications for mental health have the potential to aid people with mental health disorders, especially depression, by providing them with tools and coping mechanisms. Adolescents and young adults, being at risk of depressive symptoms and leading mobile users, are among the main targets of using mobile applications to alleviate symptoms. OBJECTIVE: This study aimed to evaluate the impact of mobile application-based psychological interventions in reducing depression symptoms in adolescents and young adults compared to those not exposed to the intervention. METHODS: We conducted a meta-analysis focusing on mobile applications for reducing depressive symptoms. We searched two databases: MEDLINE and EMBASE and included randomized controlled trials conducted in English among participants aged 18-35 years old who were assessed for depressive symptoms using a validated screening measure and used mobile applications-based psychological interventions. Two of six independent reviewers conducted study selection, data extraction, and bias assessment. A pooled mean standardized difference (Cohen's d) and 95% CI were calculated using random-effects meta-analysis. Risk of bias was assessed using I2 statistics and forest plot. Egger's test was used for assessing publication bias. RESULTS: After screening 740 references, we identified 12 trials with 1869 participants, with a mean age of participants ranging from 14.70 to 25.1 years. The interventions ranged from cognitive behavioral therapy (CBT)-based mobile apps to interactive story-telling apps and apps delivering a mix of CBT, interpersonal psychotherapy for adolescents, and dialectical behavior therapy elements. Control groups included information-only, waitlist, no intervention, and treatment as usual. Seven studies used Patient Health Questionnaire-9 (PHQ-9) to assess the severity of depressive symptoms, while the other five used different scales. There was no evidence of publication bias (p = 0.325). The mobile applications reduced depression score by 0.08 units of standardized difference more than the control, with a 95% CI of -0.19 to 0.03 (p = 0.294, I2 = 15.4%) using standardized mean difference (SMD) as the effect estimate. In a sensitivity analysis including only studies that used PHQ-9, we found a similar trend, SMD -0.72 (95%CI -1.48 to 0.03). However, both findings were not significant. CONCLUSIONS: Current evidence is insufficient to support mobile applications to relieve depression symptoms in adolescents and young adults. Further trials with larger sample size are needed to confirm our findings of a positive trend. With emerging technologies and the high exposure of apps in this population, mobile applications for depression hold promise for the future of treatment and awareness of mental health disorders in this population.

4.
iScience ; 27(8): 110543, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39175779

RESUMO

This study investigated whether lower extremity stiffness plays a role in the enhancement of change of direction speed (CODS) and the duration of this enhancement after dynamic loaded warm-up (DLWU). Fifteen badminton athletes underwent DLWU, and CODS, individual muscle and tendon stiffness, and vertical stiffness were measured before DLWU and 6, 12, and 18 min after DLWU. The data were analyzed using ANOVA and covariance analysis. Significant improvements in CODS were found at 6, 12, and 18 min post-DLWU compared to pre-DLWU (p < 0.05). The Achilles tendon stiffness of the dominant leg increased at 6 min (p = 0.039) and 18 min (p = 0.024) post-DLWU compared to pre-DLWU. Achilles tendon stiffness of the dominant leg had a significant effect on improving CODS (p > 0.05). CODS improvement lasted up to 18 min after DLWU in badminton athletes, potentially related to increased Achilles tendon stiffness of the dominant leg.

5.
Gut Microbes ; 16(1): 2389320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39150987

RESUMO

The intestinal barrier, an indispensable guardian of gastrointestinal health, mediates the intricate exchange between internal and external environments. Anchored by evolutionarily conserved junctional complexes, this barrier meticulously regulates paracellular permeability in essentially all living organisms. Disruptions in intestinal junctional complexes, prevalent in inflammatory bowel diseases and irritable bowel syndrome, compromise barrier integrity and often lead to the notorious "leaky gut" syndrome. Critical to the maintenance of the intestinal barrier is a finely orchestrated network of intrinsic and extrinsic factors that modulate the expression, composition, and functionality of junctional complexes. This review navigates through the composition of key junctional complex components and the common methods used to assess intestinal permeability. It also explores the critical intracellular signaling pathways that modulate these junctional components. Lastly, we delve into the complex dynamics between the junctional complexes, microbial communities, and environmental chemicals in shaping the intestinal barrier function. Comprehending this intricate interplay holds paramount importance in unraveling the pathophysiology of gastrointestinal disorders. Furthermore, it lays the foundation for the development of precise therapeutic interventions targeting barrier dysfunction.


Assuntos
Microbioma Gastrointestinal , Mucosa Intestinal , Permeabilidade , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Animais , Junções Íntimas/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Transdução de Sinais , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia
6.
Opt Lett ; 49(15): 4154-4157, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090882

RESUMO

Due to their ultrahigh Q-factor and small mode volume, bound states in the continuum (BICs) are intriguing for the fundamental study of the strong coupling regime. However, the strong coupling generated by BICs in one metasurface is not always strong enough, which highly limits its efficiency in applications. In this work, we realize a giant strong coupling of at most 60 meV in a quasi-BICs' (Q-BICs) tetramer metasurface composed of four Si cylinders with two different sets of diagonal lengths. The Q-BICs are induced from two types of electric quadrupole (EQ), for which detuning can be flexibly controlled by manipulating the C4v symmetry breaking Δd. The giant Rabi splitting in our proposed metasurface performs more than 15 times of the previous works, which provides more possibilities for important nonlinear and quantum applications, such as nanolaser and quantum optics.

7.
Acad Pediatr ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39181503

RESUMO

OBJECTIVE: To assess whether child food allergy is associated with family food insecurity, overall, and across different income levels. METHODS: We used the 2011-2018 National Health Interview Survey, a nationally representative cross-sectional survey. The exposure was child food allergy, and our main outcome was odds of family food insecurity, which was calculated using multivariable logistic regression models adjusted for child demographics, family characteristics and survey year. We examined for effect modification by the ratio of family income to the poverty threshold using stratification and tests for statistical interaction. RESULTS: Among 83,287 children 6% had food allergy and 22% experienced family food insecurity. Child food allergy was associated with a 1.39-fold (95% confidence interval [CI]: 1.26, 1.53) increased odds of family food insecurity overall. Child food allergy was associated with a 1.46-fold (95% CI: 1.29, 1.66) increased odds of family food insecurity among children whose families lived below 200% of the federal poverty level, and a 1.26-fold (95% CI: 1.05, 1.51) increased odds of family food insecurity among children whose families lived at 200 to 399% of the federal poverty level, with no association among children whose families lived at or above 400% of the federal poverty level (P =.04 for interaction). CONCLUSION: There is an association between child food allergy and family food insecurity, and this association is modified by the ratio of family income to the poverty threshold. Improved availability and subsidy of allergen-free foods in nutrition assistance programs and food pantries are urgently needed.

8.
Opt Lett ; 49(17): 4767-4770, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39207959

RESUMO

Bound states in the continuum (BICs) on metasurfaces have garnered significant interest for their ultrahigh Q-factor potential in sensing applications. Reconfigurability and multi-band resonance are highly desirable for sensing systems. In this work, we introduce a metasurface comprising four nanocubes with different permittivity asymmetries, which can be dynamically adjusted using Ge2Sb2Te5 (GST225), a phase-change material, in the near-infrared (NIR) region. Additionally, a simulation for a liquid molecule sensor based on the metasurface shows a sensitivity of 1017 nm/RIU. This research introduces a novel, to the best of our knowledge, approach for designing multi-band, dynamically tunable quasi-BIC metasurfaces, which are good candidates for tunable, high-sensitivity biochemical sensing and nonlinear optics applications.

9.
Int J Biol Macromol ; 276(Pt 2): 133898, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019369

RESUMO

Patients may find it challenging to accept several FDA-approved drugs for Alzheimer's disease (AD) treatment due to their unaffordable prices and side effects. Despite the known antioxidant, anti-inflammatory, and microbiota-regulating effects of common buckwheat (Fagopyrum esculentum) polysaccharides (FEP), their specific role in preventing AD has not been determined. Here, this study investigated the preventive effects of FEP on AD development in AlCl3-treated rats. The physical properties of FEP were evaluated using X-ray diffraction, FTIR, TGA, DSC, monosaccharide composition, molecular weight, and scanning electron microscopy. The results demonstrated that FEP administration improved memory and learning ability in AlCl3-treated rats. Additionally, AD pathological biomarkers (APP, BACE1, Aß1-42, and p-TauSer404), inflammatory-associated proteins (IL-1ß, IL-6, TNF-α, and Iba1), and MDA and the RAGE/p38/NF-κB pathway were elevated in AlCl3-treated rats. Moreover, these effects were reversed by the upregulation of LRP1, anti-inflammatory cytokines (IL-4 and IL-10), antioxidant enzymes (SOD and catalase), and autophagy proteins (Atg5, Beclin-1, and LC3B). Furthermore, FEP treatment increased the levels of short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing microbes ([Eubacterium]_xylanophilum_group, Lachnospiraceae_NK4A136_group, Lactobacillus). Overall, FEP mitigated oxidative stress, RAGE/p38/NF-κB-mediated neuroinflammation, and AD-associated proteins by upregulating autophagy and SCFA levels, which led to the amelioration of cognitive impairment through microbiota-gut-brain communication in AlCl3-treated rats.


Assuntos
Cloreto de Alumínio , Disfunção Cognitiva , Disbiose , Fagopyrum , NF-kappa B , Polissacarídeos , Transdução de Sinais , Animais , Ratos , Disbiose/induzido quimicamente , Fagopyrum/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Masculino , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Ratos Sprague-Dawley , Modelos Animais de Doenças
10.
Support Care Cancer ; 32(8): 501, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985345

RESUMO

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.


Assuntos
Suplementos Nutricionais , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Autoeficácia , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Inquéritos e Questionários , Idoso , Adulto , Neoplasias do Sistema Digestório/cirurgia , Neoplasias do Sistema Digestório/psicologia , Apoio Social , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/psicologia , Período Pós-Operatório
11.
Front Neurol ; 15: 1371827, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011361

RESUMO

Aim: This study aimed to investigate the associations of serum lactate level [within and after 24 h of the intensive care unit (ICU) admission] and lactate clearance rate with delirium and assess associations of lactate and lactate clearance rate with 30-day mortality in delirium patients. Methods: Data in this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database in 2012-2019. The associations of lactate and lactate clearance rate with delirium were explored through univariable and multivariable logistic regression analyses, whereas the associations of lactate and lactate clearance rate with 30-day mortality in delirium patients were investigated using univariable and multivariable Cox regression analyses. Subgroup analysis was performed for age, gender, sepsis, hypertension, sedative drug, ventilation, antibiotic drug, vasopressors, and the Sequential Organ Failure Assessment (SOFA) score. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). Results: Among 7,812 (14.58%) eligible participants, 4,338 (8.19%) had delirium and 1,903 (24.36%) died within 30 days. After adjusting for covariates, patients with lactic acidosis (lactate level > 5 mmol/L and PH < 7.35) at T0 (within 24 h of the ICU admission) had higher odds of delirium (OR = 1.235, 95%CI: 1.105-1.382). Hyperlactatemia (lactate level 2-5 mmol/L and PH > 7.35) at T1 (after 24 h of the ICU admission) was also associated with higher odds of delirium (OR = 1.277, 95%CI: 1.126-1.447). Lactate clearance rate > 50% was linked to lower odds of delirium (OR = 0.705, 95%CI: 0.613-0.811), and this relationship was also observed in ≥65 years old, female, male, non-sepsis, sepsis, non-hypertension, non-sedative drug use, sedative drug use, ventilation, antibiotic drug use, use of vasopressors, and different SOFA score subgroups (all p < 0.05). Additionally, hyperlactatemia and lactic acidosis (whether at T0 or T1) may be potential risk factors for 30-day mortality in delirium patients, whereas lactate clearance rate ≥ 0 had a potential protective effect on 30-day mortality (all p < 0.05). Conclusion: Higher serum lactate levels in the early stage of the ICU were associated with a higher risk of delirium and subsequent mortality. Measures taken to increase the lactate clearance rate are necessary to reduce potential delirium or mortality risk in clinical settings. However, more evidence from prospective studies is needed to verify these findings.

12.
Arch Microbiol ; 206(7): 289, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847838

RESUMO

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.


Assuntos
Antibacterianos , Biofilmes , Diclofenaco , Staphylococcus epidermidis , Biofilmes/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/fisiologia , Diclofenaco/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Anti-Inflamatórios não Esteroides/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Humanos , Polissacarídeos Bacterianos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
13.
mSphere ; 9(6): e0031724, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38837389

RESUMO

The emerging prevalence of drug-resistant Staphylococcus aureus isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in S. aureus, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against S. aureus. Isorhapontigenin effectively inhibits the hemolytic activity of S. aureus in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of S. aureus and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating hla and upregulating the MgrA-regulated gene spa. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the hla promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The in vivo experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating S. aureus infections. IMPORTANCE: The emergence of antibiotic-resistant Staphylococcus aureus strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of S. aureus virulence represents a significant advance in anti-virulence therapy.


Assuntos
Antibacterianos , Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Infecções Estafilocócicas , Staphylococcus aureus , Fatores de Virulência , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/genética , Fatores de Virulência/genética , Antibacterianos/farmacologia , Virulência/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Animais , Camundongos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Estilbenos/farmacologia , Humanos , Macrófagos/microbiologia , Macrófagos/efeitos dos fármacos , Feminino , Camundongos Endogâmicos BALB C , Células RAW 264.7
14.
J Pharm Biomed Anal ; 248: 116259, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38870837

RESUMO

BACKGROUND: The investigation of drug disposition in tissues is critical to improving dosing strategy and maximizing treatment effectiveness, yet developing a multi-tissue bioanalytical method could be challenging due to the differences among various matrices. Herein, we developed an LC-MS/MS method tailored for the quantitation of piperacillin (PIP), cefazolin (CFZ), and cefoxitin (CFX) in rat plasma and 12 tissues, accompanied by validation data for each matrix according to the FDA and EMA guidelines. RESULTS: The method required only a small sample volume (5 µL plasma or 50-100 µL tissue homogenates) and a relatively simple protocol for simultaneous quantitation of PIP, CFZ, and CFX within different biological matrices. Mobile phase A was composed of 5 mM ammonium formate and 0.1 % formic acid in water, while mobile phase B contained 0.1 % formic acid in acetonitrile. The mobile phase was pumped through a Synergi Fusion-RP column equipped with a guard column with a gradient elution program at a 0.3 mL/min flow rate. The mass spectrometer was operated in positive ionization mode (ESI+) using multiple reaction monitoring. SIGNIFICANCE: The validated method has been successfully applied to quantify PIP, CFZ, and CFX from the plasma and tissue samples collected in a pilot rat study and will further be used in a large pharmacokinetic study. To our knowledge, this is also the first report presenting long-term, freeze-thaw, and autosampler stability data for PIP, CFZ, and CFX in rat plasma and multiple tissues.


Assuntos
Cefazolina , Cefoxitina , Piperacilina , Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Ratos , Cefazolina/sangue , Cefazolina/farmacocinética , Cefazolina/análise , Piperacilina/sangue , Piperacilina/farmacocinética , Piperacilina/análise , Cefoxitina/farmacocinética , Cefoxitina/sangue , Cefoxitina/química , Cefoxitina/análise , Cromatografia Líquida/métodos , Reprodutibilidade dos Testes , Distribuição Tecidual , Ratos Sprague-Dawley , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/análise , Masculino , Espectrometria de Massa com Cromatografia Líquida
15.
BMC Pulm Med ; 24(1): 273, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844914

RESUMO

BACKGROUND: Serum lactate dehydrogenase (LDH) is a nonspecific inflammatory biomarker and has been reported to be associated with pneumonia prognosis. This study aimed to evaluate the relationship between LDH levels and ventilator-associated pneumonia (VAP) risk in intensive care unit (ICU) patients. METHODS: This retrospective cohort study used data from the Multiparameter Intelligent Monitoring in Intensive Care database from 2001 to 2019. ICU patients aged ≥ 18 years and receiving mechanical ventilation were included. LDH levels were analyzed as continuous and categorical variables (< 210, 210-279, 279-390, > 390 IU/L), respectively. Restricted cubic spline (RCS) curves and quartiles were used to categorize LDH levels. Logistic regression and linear regression were utilized to assess the relationship of LDH levels with VAP risk and duration of mechanical ventilation, respectively. RESULTS: A total of 9,164 patients were enrolled, of which 646 (7.05%) patients developed VAP. High levels of LDH increased the risk of VAP [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.06-1.24] and LDH levels were positively correlated with the duration of mechanical ventilation [ß = 4.49, 95%CI: (3.42, 5.56)]. Moreover, patients with LDH levels of 279-390 IU/L (OR = 1.38, 95%CI: 1.08-1.76) and > 390 IU/L (OR = 1.50, 95%CI: 1.18-1.90) had a higher risk of VAP than patients with LDH levels < 210 IU/L. Patients with LDH levels of 279-390 IU/L [ß = 3.84, 95%CI: (0.86, 6.82)] and > 390 IU/L [ß = 11.22, 95%CI: (8.21, 14.22)] (vs. <210 IU/L) had a longer duration of mechanical ventilation. CONCLUSION: Elevated serum LDH levels were related to a higher risk of VAP and longer duration of mechanical ventilation and may be useful for monitoring VAP risk.


Assuntos
Bases de Dados Factuais , Unidades de Terapia Intensiva , L-Lactato Desidrogenase , Pneumonia Associada à Ventilação Mecânica , Respiração Artificial , Humanos , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/sangue , Masculino , Feminino , Pessoa de Meia-Idade , L-Lactato Desidrogenase/sangue , Estudos Retrospectivos , Respiração Artificial/estatística & dados numéricos , Respiração Artificial/efeitos adversos , Idoso , Adulto , Fatores de Risco , Biomarcadores/sangue , Modelos Logísticos
16.
Redox Biol ; 73: 103176, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38705094

RESUMO

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.


Assuntos
Ferroptose , NADP , Humanos , NADP/metabolismo , Animais , Aciltransferases/metabolismo , Aciltransferases/genética , Camundongos , Processamento de Proteína Pós-Traducional
17.
Opt Lett ; 49(10): 2641-2644, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748125

RESUMO

Mid-infrared (MIR) Si-based optoelectronics has wide potential applications, and its design requires simultaneous consideration of device performance optimization and the feasibility of heterogeneous integration. The emerging interest in all-dielectric metasurfaces for optoelectronic applications stems from their exceptional ability to manipulate light. In this Letter, we present our research on an InSb all-dielectric metasurface designed to achieve ultrahigh absorptivity within the 5-5.5 µm wavelength range. By integrating an InSb nanodisk array layer on a Si platform using wafer bonding and heteroepitaxial growth, we demonstrate three kinds of metasurface with high absorptivity of 98.36%, 99.28%, and 99.18%. The enhanced absorption is mainly contributed by the Kerker effect and the anapole state and the peak, with the added flexibility of tuning both the peak and bandwidth of absorption by altering the metasurface parameters. Our findings provide an alternative scheme to develop high-performance detectors and absorbers for MIR silicon photonics.

18.
Chem Soc Rev ; 53(11): 5366-5393, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38712843

RESUMO

Transition metal-containing materials with aggregation-induced emission (AIE) have brought new opportunities for the development of biological probes, optoelectronic materials, stimuli-responsive materials, sensors, and detectors. Coordination compounds containing the platinum metal have emerged as a promising option for constructing effective AIE platinum complexes. In this review, we classified AIE platinum complexes based on the number of ligands. We focused on the development and performance of AIE platinum complexes with different numbers of ligands and discussed the impact of platinum ion coordination and ligand structure variation on the optoelectronic properties. Furthermore, this review analyzes and summarizes the influence of molecular geometries, stacking models, and aggregation environments on the optoelectronic performance of these complexes. We provided a comprehensive overview of the AIE mechanisms exhibited by various AIE platinum complexes. Based on the unique properties of AIE platinum complexes with different numbers of ligands, we systematically summarized their applications in electronics, biological fields, etc. Finally, we illustrated the challenges and opportunities for future research on AIE platinum complexes, aiming at giving a comprehensive summary and outlook on the latest developments of functional AIE platinum complexes and also encouraging more researchers to contribute to this promising field.

19.
Psychiatry Res ; 337: 115970, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810537

RESUMO

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.


Assuntos
COVID-19 , Transtornos do Olfato , Transtornos Relacionados ao Uso de Substâncias , Distúrbios do Paladar , Humanos , Feminino , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade , Adulto , Distúrbios do Paladar/etiologia , Distúrbios do Paladar/epidemiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Idoso , Anosmia/etiologia , Anosmia/fisiopatologia , Anosmia/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Estados Unidos/epidemiologia , Adulto Jovem
20.
Neurophotonics ; 11(2): 024207, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577628

RESUMO

Significance: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+ concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+ concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities for in vitro and in vivo fluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy. Aim: We describe the development and applications of T-GECO1-a high-performance blue-shifted GECI based on the Clavularia sp.-derived mTFP1. Approach: We use protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performance in vitro using one-photon excitation in cultured rat hippocampal neurons, in vivo using one-photon excitation fiber photometry in mice, and ex vivo using two-photon Ca2+ imaging in hippocampal slices. Results: The Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1 cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold, and the apparent Kd for Ca2+ is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled the detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant. Conclusions: T-GECO1 is a high-performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.

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