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1.
Trends Genet ; 39(6): 451-461, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36872184

RESUMEN

A large number of studies have established a causal relationship between the gut microbiota and human disease. In addition, the composition of the microbiota is substantially influenced by the human genome. Modern medical research has confirmed that the pathogenesis of various diseases is closely related to evolutionary events in the human genome. Specific regions of the human genome known as human accelerated regions (HARs) have evolved rapidly over several million years since humans diverged from a common ancestor with chimpanzees, and HARs have been found to be involved in some human-specific diseases. Furthermore, the HAR-regulated gut microbiota has undergone rapid changes during human evolution. We propose that the gut microbiota may serve as an important mediator linking diseases to human genome evolution.


Asunto(s)
Microbioma Gastrointestinal , Hominidae , Microbiota , Animales , Humanos , Microbioma Gastrointestinal/genética , Genoma Humano/genética , Hominidae/genética , Pan troglodytes/genética , Evolución Molecular
2.
PLoS Genet ; 19(6): e1010814, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37384781

RESUMEN

Meta-diamides (e.g. broflanilide) and isoxazolines (e.g. fluralaner) are novel insecticides that target the resistant to dieldrin (RDL) subunit of insect γ-aminobutyric acid receptors (GABARs). In this study, we used in silico analysis to identify residues that are critical for the interaction between RDL and these insecticides. Substitution of glycine at the third position (G3') in the third transmembrane domain (TMD3) with methionine (G3'M TMD3), which is present in vertebrate GABARs, had the strongest effect on fluralaner binding. This was confirmed by expression of RDL from the rice stem borer, Chilo suppressalis (CsRDL) in oocytes of the African clawed frog, Xenopus laevis, where the G3'MTMD3 mutation almost abolished the antagonistic action of fluralaner. Subsequently, G3'MTMD3 was introduced into the Rdl gene of the fruit fly, Drosophila melanogaster, using the CRISPR/Cas9 system. Larvae of heterozygous lines bearing G3'MTMD3 did not show significant resistance to avermectin, fipronil, broflanilide, and fluralaner. However, larvae homozygous for G3'MTMD3 were highly resistant to broflanilide and fluralaner whilst still being sensitive to fipronil and avermectin. Also, homozygous lines showed severely impaired locomotivity and did not survive to the pupal stage, indicating a significant fitness cost associated with G3'MTMD3. Moreover, the M3'GTMD3 mutation in the mouse Mus musculus α1ß2 GABAR increased sensitivity to fluralaner. Taken together, these results provide convincing in vitro and in vivo evidence for both broflanilide and fluralaner acting on the same amino acid site, as well as insights into potential mechanisms leading to target-site resistance to these insecticides. In addition, our findings could guide further modification of isoxazolines to achieve higher selectivity for the control of insect pests with minimal effects on mammals.


Asunto(s)
Insecticidas , Receptores de GABA , Animales , Ratones , Receptores de GABA/genética , Receptores de GABA/metabolismo , Dieldrín , Insecticidas/farmacología , Insecticidas/química , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Larva/metabolismo , Mamíferos/metabolismo
3.
Proc Natl Acad Sci U S A ; 120(51): e2312714120, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38079548

RESUMEN

Hydrofluoroolefins are being adopted as sustainable alternatives to long-lived fluorine- and chlorine-containing gases and are finding current or potential mass-market applications as refrigerants, among a myriad of other uses. Their olefinic bond affords relatively rapid reaction with hydroxyl radicals present in the atmosphere, leading to short lifetimes and proportionally small global warming potentials. However, this type of functionality also allows reaction with ozone, and whilst these reactions are slow, we show that the products of these reactions can be extremely long-lived. Our chamber measurements show that several industrially important hydrofluoroolefins produce CHF3 (fluoroform, HFC-23), a potent, long-lived greenhouse gas. When this process is accounted for in atmospheric chemical and transport modeling simulations, we find that the total radiative effect of certain compounds can be several times that of the direct radiative effect currently recommended by the World Meteorological Organization. Our supporting quantum chemical calculations indicate that a large range of exothermicity is exhibited in the initial stages of ozonolysis, which has a powerful influence on the CHF3 yield. Furthermore, we identify certain molecular configurations that preclude the formation of long-lived greenhouse gases. This demonstrates the importance of product quantification and ozonolysis kinetics in determining the overall environmental impact of hydrofluoroolefin emissions.

4.
Hum Genet ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850429

RESUMEN

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

5.
Anal Chem ; 96(24): 10092-10101, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38833634

RESUMEN

Tumor patients-derived organoids, as a promising preclinical prediction model, have been utilized to evaluate ex vivo drug responses for formulating optimal therapeutic strategies. Detecting adenosine triphosphate (ATP) has been widely used in existing organoid-based drug response tests. However, all commercial ATP detection kits containing the cell lysis procedure can only be applied for single time point ATP detection, resulting in the neglect of dynamic ATP variations in living cells. Meanwhile, due to the limited number of viable organoids from a single patient, it is impractical to exhaustively test all potential time points in search of optimal ones. In this work, a multifunctional microfluidic chip was developed to perform all procedures of organoid-based drug response tests, including establishment, culturing, drug treatment, and ATP monitoring of organoids. An ATP sensor was developed to facilitate the first successful attempt on whole-course monitoring the growth status of fragile organoids. To realize a clinically applicable automatic system for the drug testing of lung cancer, a microfluidic chip based automated system was developed to perform entire organoid-based drug response test, bridging the gap between laboratorial manipulation and clinical practices, as it outperformed previous methods by improving data repeatability, eliminating human error/sample loss, and more importantly, providing a more accurate and comprehensive evaluation of drug effects.


Asunto(s)
Adenosina Trifosfato , Dispositivos Laboratorio en un Chip , Organoides , Humanos , Organoides/citología , Organoides/efectos de los fármacos , Organoides/metabolismo , Adenosina Trifosfato/análisis , Adenosina Trifosfato/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Técnicas Analíticas Microfluídicas/instrumentación , Automatización
6.
Biochem Biophys Res Commun ; 694: 149468, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38183876

RESUMEN

Heart diseases are a major cause of morbidity and mortality worldwide. Understanding the molecular mechanisms underlying these diseases is essential for the development of effective diagnostic and therapeutic strategies. The FHL family consists of five members: FHL1, FHL2, FHL3, FHL4, and FHL5/Act. These members exhibit different expression patterns in various tissues including the heart. FHL family proteins are implicated in cardiac remodeling, regulation of metabolic enzymes, and cardiac biomechanical stress perception. A large number of studies have explored the link between FHL family proteins and cardiac disease, skeletal muscle disease, and ovarian metabolism, but a comprehensive and in-depth understanding of the specific molecular mechanisms targeting FHL on cardiac disease is lacking. The aim of this review is to explore the structure and function of FHL family members, to comprehensively elucidate the mechanisms by which they regulate the heart, and to explore in depth the changes in FHL family members observed in different cardiac disorders, as well as the effects of mutations in FHL proteins on heart health.


Asunto(s)
Cardiopatías , Enfermedades Musculares , Humanos , Proteínas Musculares/metabolismo , Enfermedades Musculares/genética , Cardiopatías/genética , Mutación , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas con Dominio LIM/genética
7.
Artículo en Inglés | MEDLINE | ID: mdl-38615974

RESUMEN

OBJECTIVE: Assess the efficacy of an 8-week virtual, physiotherapist (PT)-guided knee health program (Stop OsteoARthritis (SOAR)) to improve knee extensor strength in individuals at risk of post-traumatic knee osteoarthritis (PTOA). METHOD: In this superiority, randomized delayed-control trial, persons aged 16-35 years, 1-4 years after a self-reported knee joint injury were randomly assigned (1:1) to receive the SOAR program immediately (experimental group) or after a 9-week delay (control group). SOAR includes 1) one-time Knee Camp (virtual PT-guided group education, knee assessment, 1:1 exercise and physical activity (PA) goal-setting); 2) Weekly personalized home-based exercise and PA program with tracking; 3) Weekly 1:1 PT counseling (virtual). The primary outcome was a change in isokinetic knee extensor strength (baseline to 9-weeks). Additional outcomes included change in self-reported knee-related quality-of-life (QOL), self-efficacy, self-management and kinesiophobia, and PA (accelerometer) at 9 and 18-weeks. Linear regression models estimated the effect of the 8-week intervention at the primary endpoint (9-week). RESULTS: 49 of 54 randomized participants completed the study (91%). Participants were a mean ± standard deviation age of 27 ± 5.0 years, and 2.4 ± 0.9 years post-injury. No mean between group differences for the primary (0.05; 95% confidence interval (CI): -0.10, 0.19) or other outcomes were seen at 9 weeks except for greater improvements in perceived self-management (Partner in Health Scale; 11.3/96, 95%CI: 5.5, 17.1) and kinesiophobia (Tampa Scale of Kinesiophobia; -4.4/33, 95%CI: -7.0, -1.8). CONCLUSION: For active persons with elevated risk of PTOA, an 8-week SOAR program did not change knee-related strength, QOL, self-efficacy, or PA, on average, but may benefit the ability to self-manage knee health and kinesiophobia.

8.
Diabetes Metab Res Rev ; 40(4): e3814, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38769695

RESUMEN

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.


Asunto(s)
Diabetes Gestacional , Ácido Fólico , Metilenotetrahidrofolato Reductasa (NADPH2) , Humanos , Femenino , Diabetes Gestacional/sangre , Diabetes Gestacional/metabolismo , Embarazo , Ácido Fólico/sangre , Estudios Prospectivos , Adulto , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Biomarcadores/sangre , Estudios de Seguimiento , Ferredoxina-NADP Reductasa/genética , Genotipo , China/epidemiología , Pronóstico , Segundo Trimestre del Embarazo/sangre , Homocisteína/sangre , Homocisteína/metabolismo
9.
Microb Cell Fact ; 23(1): 89, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528536

RESUMEN

BACKGROUND: Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. RESULTS: In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. CONCLUSIONS: Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.


Asunto(s)
Endopeptidasas , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Animales , Ratones , Staphylococcus , Staphylococcus aureus , Fagos de Staphylococcus , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Biopelículas
10.
Environ Sci Technol ; 58(22): 9896-9907, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38669322

RESUMEN

Efficient use of humic acid (HA) for eco-friendly farming and environmental remediation requires further understanding of how targeted modification of HA affects the chemical structure of HA and thereby its effectiveness in enhancing soil quality. We developed novel selective modifiers (SMs) for extracting HA by codoping sodium and copper elements into the birnessite lattice. The structure of SMs was thoroughly examined, and the HAs extracted using SMs, referred to as SMHs, were subjected to a detailed evaluation of their functional groups, molecular weight, carbon composition, flocculation limits, and effectiveness in saline soil remediation. The results showed that replacing manganese with sodium and copper in SMs alters the valence state and reactive oxygen species. In contrast, SMHs exhibited increased acidic functional groups, a lower molecular weight, and transformed aliphatic carbon. Furthermore, the saline soil was improved through increased salt leaching and an optimized soil aggregate structure by SMHs. This research highlights the importance of targeted modification of HA and demonstrates the potential of these modifiers in improving soil quality for eco-friendly farming and environmental remediation.


Asunto(s)
Sustancias Húmicas , Suelo , Suelo/química , Restauración y Remediación Ambiental/métodos , Contaminantes del Suelo
11.
Colorectal Dis ; 26(3): 534-544, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38229235

RESUMEN

AIM: Prehabilitation for colorectal cancer has focused on exercise-based interventions that are typically designed by clinicians; however, no research has yet been patient-oriented. The aim of this feasibility study was to test a web-based multimodal prehabilitation intervention (known as PREP prehab) consisting of four components (physical activity, diet, smoking cessation, psychological support) co-designed with five patient partners. METHOD: A longitudinal, two-armed (website without or with coaching support) feasibility study of 33 patients scheduled for colorectal surgery 2 weeks or more from consent (January-September 2021) in the province of British Columbia, Canada. Descriptive statistics analysed a health-related quality of life questionnaire (EQ5D-5L) at baseline (n = 25) and 3 months postsurgery (n = 21), and a follow-up patient satisfaction survey to determine the acceptability, practicality, demand for and potential efficacy in improving overall health. RESULTS: Patients had a mean age of 52 years (SD 14 years), 52% were female and they had a mean body mass index of 25 kg m-2 (SD 3.8 kg m-2). Only six patients received a Subjective Global Assessment for being at risk for malnutrition, with three classified as 'severely/moderately' malnourished. The majority (86%) of patients intended to use the prehabilitation website, and nearly three-quarters (71%) visited the website while waiting for surgery. The majority (76%) reported that information, tools and resources provided appropriate support, and 76% indicated they would recommend the PREP prehab programme. About three-quarters (76%) reported setting goals for lifestyle modification: 86% set healthy eating goals, 81% aimed to stay active and 57% sought to reduce stress once a week or more. No patients contacted the team to obtain health coaching, despite broad interest (71%) in receiving active support and 14% reporting they received 'active support'. CONCLUSION: This web-based multimodal prehabilitation programme was acceptable, practical and well-received by all colorectal surgery patients who viewed the patient-oriented multimodal website. The feasibility of providing active health coaching support requires further investigation.


Asunto(s)
Neoplasias Colorrectales , Cirugía Colorrectal , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias Colorrectales/cirugía , Estudios de Factibilidad , Ejercicio Preoperatorio , Calidad de Vida , Cuidados Preoperatorios , Canadá , Internet
12.
Environ Res ; 248: 118213, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38280526

RESUMEN

Global ocean salinity is changing under rapid climate change and intensified anthropogenic activity. Increased differences in salinity threaten marine biodiversity, organismal survival, and evolution, particularly sessile invertebrates dwelling in highly fluctuating intertidal and estuarine environments. Comparing the responses of closely related species to salinity changes can provide insights into the adaptive mechanisms underlying inter- and intraspecific divergence in salinity tolerance, but are poorly understood in marine bivalves. We collected wild individuals of four Crassostrea species, in addition to two populations of the same species from their native habitats and determined the dynamics of hydrolyzed amino acids (HAAs) and transcriptional responses to hypersaline stress. In response to hypersaline stress, species/populations inhabiting natural high-salinity sea environments showed higher survival and less decline in HAAs than that of congeners inhabiting low-salinity estuaries. Thus, native environmental salinity shapes oyster tolerance. Notably, a strong negative correlation between the decline in HAAs and survival indicated that the HAAs pool could predict tolerance to hypersaline challenge. Four HAAs, including glutamine (Glu), aspartic acid (Asp), alanine (Ala) and glycine (Gly), were identified as key amino acids that contributed substantially to the emergency response to hypersaline stress. High-salinity-adapted oyster species only induced substantial decreases in Glu and Asp, whereas low-salinity-adapted congeners further incresaed Ala and Gly metabolism under hypersaline stress. The dynamics of the content and gene expression responsible for key amino acids pathways revealed the importance of maintaining the balance between energy production and ammonia detoxification in divergent hypersaline responses among oyster species/populations. High constructive or plastic expression of evolutionarily expanded gene copies in high-salinity-adapted species may contribute to their greater hypersaline tolerance. Our findings reveal the adaptive mechanism of key amino acids in salinity adaptation in marine bivalves and provide new avenues for the prediction of adaptive potential and aquaculture with high-salinity tolerant germplasms.


Asunto(s)
Crassostrea , Humanos , Animales , Crassostrea/genética , Amoníaco , Aminoácidos , Ambiente , Ecosistema , Salinidad
13.
Nutr Metab Cardiovasc Dis ; 34(7): 1631-1638, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38653673

RESUMEN

BACKGROUND AND AIMS: It has been reported that maresin 1 (MaR1) is able to protect against the development of atherogenesis in cellular and animal models. This study was performed to investigate whether plasma MaR1 is associated with the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. METHODS AND RESULTS: The study included 2822 non-ASCVD participants from a community-based cohort who were followed for about 8 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for ASCVD events according to baseline MaR1 quartiles were calculated using the Cox proportional hazards model. During follow-up, a total of 290 new ASCVD cases were identified. The restricted cubic spline analysis indicated a linear dose-response association between plasma MaR1 and incident ASCVD. In addition, the adjusted-HR (95% CI) for ASCVD events associated with one standard deviation increase in MaR1 was 0.79 (0.68-0.91). Moreover, the adjusted-HRs (95% CIs) for ASCVD events associated with the second, third and fourth quartiles versus the first quartile of plasma MaR1 were 1.00, 1.04 (0.76, 1.42), 0.88 (0.64, 1.22) and 0.58 (0.41, 0.84), respectively. Mediation analyses showed that the association between MaR1 and incident ASCVD was partially mediated by small dense low-density lipoprotein cholesterol, with a mediation proportion of 9.23%. Further, the net reclassification improvement and integrated discrimination improvement of ASCVD risk were significantly improved when MaR1 was added to basic model established by conventional risk factors (all p < 0.01). CONCLUSIONS: Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development.


Asunto(s)
Aterosclerosis , Biomarcadores , Ácidos Docosahexaenoicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Medición de Riesgo , Incidencia , China/epidemiología , Biomarcadores/sangre , Anciano , Factores de Tiempo , Ácidos Docosahexaenoicos/sangre , Adulto , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores Protectores , Pueblos del Este de Asia
14.
Clin Exp Nephrol ; 28(2): 125-135, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37847437

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy. This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns. CONCLUSION: Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperpotasemia , Insuficiencia Renal Crónica , Animales , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Hiperpotasemia/inducido químicamente , Hiperpotasemia/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/inducido químicamente , Naftiridinas/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones
15.
Biol Res ; 57(1): 28, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750549

RESUMEN

BACKGROUND: The activated microglia have been reported as pillar factors in neuropathic pain (NP) pathology, but the molecules driving pain-inducible microglial activation require further exploration. In this study, we investigated the effect of dorsal root ganglion (DRG)-derived exosomes (Exo) on microglial activation and the related mechanism. METHODS: A mouse model of NP was generated by spinal nerve ligation (SNL), and DRG-derived Exo were extracted. The effects of DRG-Exo on NP and microglial activation in SNL mice were evaluated using behavioral tests, HE staining, immunofluorescence, and western blot. Next, the differentially enriched microRNAs (miRNAs) in DRG-Exo-treated microglia were analyzed using microarrays. RT-qPCR, RNA pull-down, dual-luciferase reporter assay, and immunofluorescence were conducted to verify the binding relation between miR-16-5p and HECTD1. Finally, the effects of ubiquitination modification of HSP90 by HECTD1 on NP progression and microglial activation were investigated by Co-IP, western blot, immunofluorescence assays, and rescue experiments. RESULTS: DRG-Exo aggravated NP resulting from SNL in mice, promoted the activation of microglia in DRG, and increased neuroinflammation. miR-16-5p knockdown in DRG-Exo alleviated the stimulating effects of DRG-Exo on NP and microglial activation. DRG-Exo regulated the ubiquitination of HSP90 through the interaction between miR-16-5p and HECTD1. Ubiquitination alteration of HSP90 was involved in microglial activation during NP. CONCLUSIONS: miR-16-5p shuttled by DRG-Exo regulated the ubiquitination of HSP90 by interacting with HECTD1, thereby contributing to the microglial activation in NP.


Asunto(s)
Modelos Animales de Enfermedad , Exosomas , Ganglios Espinales , Proteínas HSP90 de Choque Térmico , MicroARNs , Microglía , Neuralgia , Animales , MicroARNs/metabolismo , MicroARNs/genética , Microglía/metabolismo , Exosomas/metabolismo , Neuralgia/metabolismo , Neuralgia/genética , Ganglios Espinales/metabolismo , Ratones , Proteínas HSP90 de Choque Térmico/metabolismo , Masculino , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ratones Endogámicos C57BL
16.
BMC Geriatr ; 24(1): 19, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178005

RESUMEN

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.


Asunto(s)
Pacientes Internos , Desnutrición , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Actividades Cotidianas , Evaluación Geriátrica , Estudios Retrospectivos , Desnutrición/diagnóstico , Desnutrición/epidemiología , Estado Nutricional , Evaluación Nutricional , Inflamación/diagnóstico , Inflamación/epidemiología
17.
J Ultrasound Med ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700113

RESUMEN

OBJECTIVES: The aim of this study is to determine the optimum and fine values of the number and transmission angles of tilted plane waves for coherent plane-wave compounding (CPWC)-based high local pulse wave velocity (LPWV) estimation. METHODS: A Verasonics system incorporating a linear array probe L14-5/38 with 128 elements and a pulsatile pump, CompuFlow1000, were used to acquire radio frequency data of 3, 5, 7, and 9 tilted plane wave sequences with angle intervals from 0° to 12° with a coarse interval increment step of 1°, and the angle intervals from 0° to 2° with a fine interval increment step of 0.25° from a carotid vessel phantom with the LPWV of 13.42 ± 0.90 m/s. The mean value, standard deviation, and coefficients of variation (CV) of the estimated LPWVs were calculated to quantitatively assess the performance of different configurations for CPWC-based LPWV estimation. Ten healthy human subjects of two age groups were recruited to assess the in vivo feasibility of the optimum parameter values. RESULTS: The CPWC technique with three plane waves (PRF of 12 kHz corresponding to a frame rate of 4000 Hz) with an interval of 0.75° had LPWVs of 13.52 ± 0.08 m/s with the lowest CV of 1.84% on the phantom, and 5.49 ± 1.46 m/s with the lowest CV of 12.35% on 10 subjects. CONCLUSIONS: The optimum parameters determined in this study show the best repeatability of the LPWV measurements with a vessel phantom and 10 healthy subjects, which support further studies on larger datasets for potential applications.

18.
Ecotoxicol Environ Saf ; 270: 115845, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38134638

RESUMEN

Aspirin is a widely used multi-efficiency pharmaceutical, and its environmental residues are frequently detected. However, limited information is available on its effects on the development of the public health pest and saprophytic insect Musca domestica. In this study, it was demonstrated that aspirin inhibits the larval growth of house flies in a concentration-dependent manner. Microbiome analysis indicated that the composition of larval intestinal bacteria was influenced by aspirin but not greatly. The dominant bacterial genus in the aspirin group was still Klebsiella, as in the control group. Transcriptome sequencing and gene set enrichment analysis showed that retinol metabolism was activated after aspirin treatment. High performance liquid chromatography indicated that the content of retinol in larvae was decreased and that of retinoic acid was increased. The addition of ß-carotene, a precursor substance of retinol, in feeding promotes larval development and alleviates the inhibitory effect caused by aspirin. In contrast, retinoic acid delayed the larval development of house flies as well as aspirin. Gene expression analysis after aspirin exposure demonstrated that genes involved in the transformation from retinol to retinoic acid were upregulated. Overall, aspirin exposure impairs larval development by activating retinol metabolism in house flies and can be utilized as an effective pesticide. This work uncovers the mechanism underlying the larval development inhibition induced by aspirin in terms of metabolism and genetics, and provides novel functional exploration of a traditional drug for pest management.


Asunto(s)
Dípteros , Moscas Domésticas , Animales , Moscas Domésticas/genética , Moscas Domésticas/microbiología , Larva , Vitamina A , Tretinoina
19.
Ecotoxicol Environ Saf ; 272: 116077, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38335578

RESUMEN

Vermicomposting via housefly larvae can be used to efficiently treat manure and regenerate biofertilizer; however, the uptake of heavy metals could negatively influence the growth and development of larvae. Intestinal bacteria play an important role in the development of houseflies, but their effects on resistance to heavy metal damage in houseflies are still poorly understood. In this study, the life history traits and gut microbiota of housefly larvae were evaluated after exposure to an environment with Cu2+ -Enterobacter hormaechei. The data showed that exposure to 300 µg/mL Cu2+ significantly inhibited larval development and locomotor activity and reduced immune capacity. However, dietary supplementation with a Cu2+ -Enterobacter hormaechei mixture resulted in increased body weight and length, and the immune capacity of the larvae returned to normal levels. The abundances of Providencia and Klebsiella increased when larvae were fed Cu2+ -contaminated diets, while the abundances of Enterobacter and Bacillus increased when larvae were exposed to a Cu2+ -Enterobacter hormaechei mixture-contaminated environment. In vitro scanning electron microscopy analysis revealed that Enterobacter hormaechei exhibited obvious adsorption of Cu2+ when cultured in the presence of Cu2+, which reduced the damage caused by Cu2+ to other bacteria in the intestine and protected the larvae from Cu2+ injury. Overall, our results showed that Enterobacter hormaechei can absorb Cu2+ and increase the abundance of beneficial bacteria, thus protecting housefly larvae from damage caused by Cu2+. These results may fill the gaps in our understanding of the interactions between heavy metals and beneficial intestinal bacteria, offering valuable insights into the interplay between housefly larvae and metal contaminants in the environment. This approach could enhance the efficiency of converting manure contaminated with heavy metals to resources using houseflies.


Asunto(s)
Moscas Domésticas , Metales Pesados , Animales , Moscas Domésticas/microbiología , Larva , Estiércol/microbiología , Metales Pesados/toxicidad , Enterobacter
20.
J Adv Nurs ; 80(1): 339-349, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37449572

RESUMEN

BACKGROUND: Providing a favourable practice environment has been regarded as an essential to improve the job outcomes of newly graduated nurses (NGNs). However, little is known about how and when NGNs can best utilize their practice environment to produce optimal job outcomes. AIM: The aim of this study, which is based on the Conservation of Resources Theory and the Social Cognitive Model of Career Self-Management, is to investigate whether NGNs who have a higher level of personal growth initiative are more likely to benefit from their practice environment and achieve better job outcomes by increasing their occupational self-efficacy. DESIGN: A cross-sectional study. METHODS: From 1 September 2022, to 30 September 2022, 279 NGNs from five Chinese state-owned hospitals were recruited for this study. The participants completed measures of practice environment, personal growth initiative, occupational self-efficacy, job stress, job satisfaction, turnover intention and quality of care. A descriptive analysis and a moderated mediation model were computed. Reporting adhered to the STROBE statement. RESULTS: The influence of the practice environment on job outcomes was significantly mediated by occupational self-efficacy, with personal growth initiative acting as a moderator of this mediation effect. CONCLUSIONS: NGNs who exhibited a higher degree of personal growth initiative were more likely to derive benefits from their practice environment and attain positive job outcomes by enhancing their occupational self-efficacy. To boost NGNs' occupational self-efficacy and achieve optimal job outcomes, hospital administrators may not only provide a supportive practice environment for them but also conduct interventions that promote their personal growth initiative. NO PATIENT OR PUBLIC CONTRIBUTION: This study was designed to examine the psychosocial factors associated with NGNs' job outcomes. The study was not conducted using suggestions from the patient groups or the public. IMPACTS: Our findings indicate that favourable practise contexts may not always benefit the nursing job outcome if NGNs do not exhibit a high level of personal growth initiative and produce increased occupational self-efficacy. Therefore, hospital administrators should consider implementing an intervention to improve the personal growth initiative of NGNs so that they can take full advantage of the practice environment and gain resources at work to create optimal job outcomes.


Asunto(s)
Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Estrés Laboral , Humanos , Estudios Transversales , Autoeficacia , Satisfacción en el Trabajo , Reorganización del Personal , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología
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