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1.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38549133

RESUMEN

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Asunto(s)
Propofol , Sepsis , Ratones , Humanos , Animales , Propofol/farmacología , Propofol/uso terapéutico , Propofol/metabolismo , Receptor Toll-Like 4/metabolismo , Modelos Animales de Enfermedad , Macrófagos/metabolismo , Sepsis/complicaciones , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo
2.
Plant Physiol ; 192(2): 1483-1497, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-36810650

RESUMEN

Glandular secretory trichomes (GSTs) can secrete and store a variety of specific metabolites. By increasing GST density, valuable metabolites can be enhanced in terms of productivity. However, the comprehensive and detailed regulatory network of GST initiation still needs further investigation. By screening a complementary DNA library derived from young leaves of Artemisia annua, we identified a MADS-box transcription factor, AaSEPALLATA1 (AaSEP1), that positively regulates GST initiation. Overexpression of AaSEP1 in A. annua substantially increased GST density and artemisinin content. The HOMEODOMAIN PROTEIN 1 (AaHD1)-AaMYB16 regulatory network regulates GST initiation via the jasmonate (JA) signaling pathway. In this study, AaSEP1 enhanced the function of AaHD1 activation on downstream GST initiation gene GLANDULAR TRICHOME-SPECIFIC WRKY 2 (AaGSW2) through interaction with AaMYB16. Moreover, AaSEP1 interacted with the JA ZIM-domain 8 (AaJAZ8) and served as an important factor in JA-mediated GST initiation. We also found that AaSEP1 interacted with CONSTITUTIVE PHOTOMORPHOGENIC 1 (AaCOP1), a major repressor of light signaling. In this study, we identified a MADS-box transcription factor that is induced by JA and light signaling and that promotes the initiation of GST in A. annua.


Asunto(s)
Artemisia annua , Tricomas , Tricomas/genética , Tricomas/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ciclopentanos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Br J Anaesth ; 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38527923

RESUMEN

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.

4.
BMC Womens Health ; 24(1): 341, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877419

RESUMEN

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Menopausia , Selenio , Humanos , Femenino , Selenio/sangre , Estudios Transversales , Persona de Mediana Edad , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Menopausia/sangre , Resistencia a la Insulina/fisiología , Ayuno/sangre , Prevalencia , Posmenopausia/sangre , Premenopausia/sangre
5.
BMC Public Health ; 24(1): 743, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459526

RESUMEN

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.


Asunto(s)
Diabetes Mellitus Tipo 2 , Selenio , Masculino , Femenino , Humanos , Persona de Mediana Edad , Preescolar , Diabetes Mellitus Tipo 2/epidemiología , Glándula Tiroides , Encuestas Nutricionales , Autoinmunidad , Estudios Prospectivos , Estudios Transversales
6.
Gut ; 73(1): 78-91, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-37553229

RESUMEN

OBJECTIVE: The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. Akkermansia muciniphila (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development. DESIGN: Relative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis. RESULTS: We first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model. CONCLUSION: We revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice.


Asunto(s)
Sepsis , Receptor Toll-Like 4 , Porcinos , Humanos , Ratones , Animales , Receptor Toll-Like 4/metabolismo , Sepsis/prevención & control , Transducción de Señal , Verrucomicrobia
7.
Eur Respir J ; 61(2)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36229053

RESUMEN

INTRODUCTION: Acute lung injury (ALI) is a major cause of morbidity and mortality after intestinal ischaemia/reperfusion (I/R). The gut microbiota and its metabolic byproducts act as important modulators of the gut-lung axis. This study aimed to define the role of succinate, a key microbiota metabolite, in intestinal I/R-induced ALI progression. METHODS: Gut and lung microbiota of mice subjected to intestinal I/R were analysed using 16S rRNA gene sequencing. Succinate level alterations were measured in germ-free mice or conventional mice treated with antibiotics. Succinate-induced alveolar macrophage polarisation and its effects on alveolar epithelial apoptosis were evaluated in succinate receptor 1 (Sucnr1)-deficient mice and in murine alveolar macrophages transfected with Sucnr1-short interfering RNA. Succinate levels were measured in patients undergoing cardiopulmonary bypass, including intestinal I/R. RESULTS: Succinate accumulated in lungs after intestinal I/R, and this was associated with an imbalance of succinate-producing and succinate-consuming bacteria in the gut, but not the lungs. Succinate accumulation was absent in germ-free mice and was reversed by gut microbiota depletion with antibiotics, indicating that the gut microbiota is a source of lung succinate. Moreover, succinate promoted alveolar macrophage polarisation, alveolar epithelial apoptosis and lung injury during intestinal I/R. Conversely, knockdown of Sucnr1 or blockage of SUCNR1 in vitro and in vivo reversed the effects of succinate by modulating the phosphoinositide 3-kinase-AKT/hypoxia-inducible factor-1α pathway. Plasma succinate levels significantly correlated with intestinal I/R-related lung injury after cardiopulmonary bypass. CONCLUSION: Gut microbiota-derived succinate exacerbates intestinal I/R-induced ALI through SUCNR1-dependent alveolar macrophage polarisation, identifying succinate as a novel target for gut-derived ALI in critically ill patients.


Asunto(s)
Lesión Pulmonar Aguda , Microbioma Gastrointestinal , Daño por Reperfusión , Ratones , Animales , Ácido Succínico/metabolismo , Fosfatidilinositol 3-Quinasas , ARN Ribosómico 16S/genética , Lesión Pulmonar Aguda/complicaciones , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Reperfusión , Isquemia/complicaciones , Ratones Endogámicos C57BL
8.
J Transl Med ; 21(1): 264, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37072757

RESUMEN

BACKGROUND: Lactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus (L. murinus)-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus-derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism. METHODS: Liquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids. RESULTS: By comparing the fecal contents of three L. murinus-derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury. CONCLUSIONS: The content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.


Asunto(s)
Microbiota , Daño por Reperfusión , Ratones , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Triptófano/farmacología , Triptófano/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Estrés Oxidativo , Isquemia
9.
J Med Virol ; 95(1): e28267, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319439

RESUMEN

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.


Asunto(s)
Bacteriófagos , Cardiomiopatías , Microbioma Gastrointestinal , Sepsis , Humanos , Estudios de Casos y Controles , Disbiosis/complicaciones , Cardiomiopatías/etiología , Bacterias/genética , Sepsis/complicaciones
10.
J Surg Res ; 287: 72-81, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36870304

RESUMEN

INTRODUCTION: The clinical importance of postoperative acute kidney injury (AKI) in patients undergoing general thoracic surgery is unclear. We aimed to systematically review the incidence, risk factors, and prognostic implications of AKI as a complication after general thoracic surgery. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from January 2004 to September 2021. Observational or interventional studies that enrolled ≥50 patients undergoing general thoracic surgery and reported postoperative AKI defined using contemporary consensus criteria were included for meta-analysis. RESULTS: Thirty-seven articles reporting 35 unique cohorts were eligible. In 29 studies that enrolled 58,140 consecutive patients, the pooled incidence of postoperative AKI was 8.0% (95% confidence interval [CI]: 6.2-10.0). The incidence was 3.8 (2.0-6.2) % after sublobar resection, 6.7 (4.1-9.9) % after lobectomy, 12.1 (8.1-16.6) % after bilobectomy/pneumonectomy, and 10.5 (5.6-16.7) % after esophagectomy. Considerable heterogeneity in reported incidences of AKI was observed across studies. Short-term mortality was higher (unadjusted risk ratio: 5.07, 95% CI: 2.99-8.60) and length of hospital stay was longer (weighted mean difference: 3.53, 95% CI: 2.56-4.49, d) in patients with postoperative AKI (11 studies, 28,480 patients). Several risk factors for AKI after thoracic surgery were identified. CONCLUSIONS: AKI occurs frequently after general thoracic surgery and is associated with increased short-term mortality and length of hospital stay. For patients undergoing general thoracic surgery, AKI may be an important postoperative complication that needs early risk evaluation and mitigation.


Asunto(s)
Lesión Renal Aguda , Cirugía Torácica , Procedimientos Quirúrgicos Torácicos , Humanos , Procedimientos Quirúrgicos Torácicos/efectos adversos , Neumonectomía , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
11.
Environ Res ; 216(Pt 2): 114442, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36202245

RESUMEN

The utilization of solid waste for resource recovery and production of value-added products is the theme of green chemistry. Currently, how to using solid wastes to prepare environmentally-functional materials with high performance and strength is one of the hot topics. In this research, electrolytic manganese residue (EMR) was thermally activated with calcite to prepare a silicon-based functionalized adsorbent (C-EMR) for the removal of cadmium (Cd2+, 467.14 mg/g) and lead (Pb2+, 972 mg/g). The thermodynamic results indicated that the removal process of Cd2+ and Pb2+ by C-EMR were endothermic and spontaneous. HNO3 can effectively strip the two adsorbed metals from C-EMR with the stripping efficiency of nearly 80% for Cd2+ and 99.92% for Pb2+, indicating that adsorption and ion exchange may be the main reason for the removal of the metals on C-EMR. Besides, surface precipitation was also responsible for removing some Pb2+ from the aquatic environment according to the X-ray photoelectron spectrometry (XPS) analysis. Results indicate that -SiO3- has stronger affinity with Pb2+ and Cd2+ than other groups ((-MnO2), -OH) by theoretical calculation (VASP, GGA-PBE). This study shows that this novel adsorbent (C-EMR) can be adopted as an environmentally-friendly, inexpensive and efficient adsorbent for removal of Cd2+ and Pb2+ from aquatic solution. This technique not only provides potential adsorbent for the elimination of heavy metals but also proposes an alternative route for the treatment and utilization of waste solid.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Adsorción , Cadmio/análisis , Compuestos de Manganeso/química , Plomo , Contaminantes Químicos del Agua/análisis , Óxidos/química , Metales Pesados/química , Cinética , Concentración de Iones de Hidrógeno
12.
Anesth Analg ; 137(5): 1019-1028, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37713328

RESUMEN

BACKGROUND: Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. METHODS: This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. RESULTS: We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women ( P = .539) or men ( P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex ( Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. CONCLUSIONS: Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

13.
Ren Fail ; 45(2): 2287130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38031451

RESUMEN

BACKGROUND: Bispectral index (BIS) is a processed electroencephalography monitoring tool and is widely used in anesthetic depth monitoring. Deep anesthesia exposure may be associated with multiple adverse outcomes. However, the relationship between anesthetic depth and postoperative acute kidney injury (AKI) remains unclear. We sought to determine the effect of BIS-based deep anesthesia duration on postoperative AKI following noncardiac surgery. METHODS: This retrospective study used data from the Vital Signs DataBase, including patients undergoing noncardiac surgeries with BIS monitoring. The BIS values were collected every second during anesthesia. Restricted cubic splines and logistic regression were used to assess the association between the cumulative duration of deep anesthesia and postoperative AKI. RESULTS: 4774 patients were eligible, and 129 (2.7%) experienced postoperative AKI. Restricted cubic splines showed that a cumulative duration of BIS < 45 was nonlinearly associated with postoperative AKI (P-overall = 0.033 and P-non-linear = 0.023). Using the group with the duration of BIS < 45 less than 15 min as the reference, ORs of postoperative AKI were 2.59 (95% confidence interval [CI]:0.60 to 11.09, p = 0.200) in the 15-100 min group, and 4.04 (95%CI:0.92 to 17.76, p = 0.064) in the ≥ 100 min group after adjusting for preoperative and intraoperative covariates in multivariable logistic regression. CONCLUSIONS: The cumulative duration of BIS < 45 was independently and nonlinearly associated with the risk of postoperative AKI in patients undergoing noncardiac surgery.


Asunto(s)
Lesión Renal Aguda , Anestesia , Anestésicos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
14.
Dig Dis Sci ; 67(5): 1794-1805, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-33839982

RESUMEN

BACKGROUND: Emerging evidence has suggested that miRNAs are important regulators of intestinal I/R injury, but their function in this context remains elusive. AIMS: To evaluate the role of miR-26b-5p in intestinal I/R injury. METHODS: We utilized in vivo murine models of intestinal I/R and in vitro Mode-K cell-based models of oxygen and glucose deprivation/reperfusion (OGD/R) to examine the function of miR-26b-5p in intestinal I/R injury. The expression of miR-26b-5p in intestinal mucosa and Mode-K cell was detected by RT-PCR. HE staining and Chiu's score were used to evaluate intestinal mucosa injury severity. Apoptosis was detected by TUNEL stain, flow cytometry, and western blot. TargetScan and StarBase prediction algorithms were applied to predict putative target genes of miR-26b-5p and validated by luciferase reporter analyses. RESULTS: We found that the expression of miR-26b-5p in intestinal mucosa was markedly decreased during I/R injury. We additionally found miR-26b-5p overexpression to markedly disrupt intestinal I/R- or OGD/R-induced injury in vivo and in vitro, whereas inhibiting this miRNA had an adverse impact and resulted in increased intestinal tissue injury and Mode-K cell damage. From a mechanistic perspective, miR-26b-5p was predicted to target DAPK1, which was related to cellular apoptosis. Luciferase reporter assay results confirmed that miR-26b-5p directly targets DAPK1 in Mode-K cells, thereby suppressing OGD/R-induced cell apoptosis. CONCLUSION: Our findings show that miR-26b-5p may prevent intestinal I/R injury via targeting DAPK1 and inhibiting intestinal mucosal cell apoptosis, suggesting that this miRNA may be a viable target for the treatment of intestinal I/R injury.


Asunto(s)
MicroARNs , Daño por Reperfusión , Animales , Apoptosis/genética , Proteínas Quinasas Asociadas a Muerte Celular/genética , Glucosa , Humanos , Mucosa Intestinal/metabolismo , Isquemia , Ratones , MicroARNs/metabolismo , Oxígeno , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control
15.
Anesth Analg ; 134(4): 699-709, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34403381

RESUMEN

BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors. METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed. RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord. CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Microbioma Gastrointestinal , Animales , Neoplasias de la Mama/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Hiperalgesia , Ratones , Modelos Estadísticos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Receptores Activados del Proliferador del Peroxisoma , Pronóstico , ARN Ribosómico 16S/genética
16.
Mar Drugs ; 20(3)2022 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-35323464

RESUMEN

Chitooligosaccharides (COSs) have been widely used in agriculture, medicine, cosmetics, and foods, which are commonly prepared from chitin with chitinases. So far, while most COSs are prepared from colloidal chitin, chitinases used in preparing COSs directly from natural crystalline chitin are less reported. Here, we characterize three chitinases, which were identified from the marine bacterium Pseudoalteromonas flavipulchra DSM 14401T, with an ability to degrade crystalline chitin into (GlcNAc)2 (N,N'-diacetylchitobiose). Strain DSM 14401 can degrade the crystalline α-chitin in the medium to provide nutrients for growth. Genome and secretome analyses indicate that this strain secretes six chitinolytic enzymes, among which chitinases Chia4287, Chib0431, and Chib0434 have higher abundance than the others, suggesting their importance in crystalline α-chitin degradation. These three chitinases were heterologously expressed, purified, and characterized. They are all active on crystalline α-chitin, with temperature optima of 45-50 °C and pH optima of 7.0-7.5. They are all stable at 40 °C and in the pH range of 5.0-11.0. Moreover, they all have excellent salt tolerance, retaining more than 92% activity after incubation in 5 M NaCl for 10 h at 4 °C. When acting on crystalline α-chitin, the main products of the three chitinases are all (GlcNAc)2, which suggests that chitinases Chia4287, Chib0431, and Chib0434 likely have potential in direct conversion of crystalline chitin into (GlcNAc)2.


Asunto(s)
Proteínas Bacterianas/química , Quitina/química , Quitinasas/química , Disacáridos/química , Pseudoalteromonas/enzimología , Proteínas Bacterianas/aislamiento & purificación , Quitinasas/aislamiento & purificación , Genoma Bacteriano , Pseudoalteromonas/genética , Cloruro de Sodio/química
17.
Plant Biotechnol J ; 19(7): 1412-1428, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33539631

RESUMEN

Artemisinin, a sesquiterpene lactone widely used in malaria treatment, was discovered in the medicinal plant Artemisia annua. The biosynthesis of artemisinin is efficiently regulated by jasmonate (JA) and abscisic acid (ABA) via regulatory factors. However, the mechanisms linking JA and ABA signalling with artemisinin biosynthesis through an associated regulatory network of downstream transcription factors (TFs) remain enigmatic. Here we report AaTCP15, a JA and ABA dual-responsive teosinte branched1/cycloidea/proliferating (TCP) TF, which is essential for JA and ABA-induced artemisinin biosynthesis by directly binding to and activating the promoters of DBR2 and ALDH1, two genes encoding enzymes for artemisinin biosynthesis. Furthermore, AaORA, another positive regulator of artemisinin biosynthesis responds to JA and ABA, interacts with and enhances the transactivation activity of AaTCP15 and simultaneously activates AaTCP15 transcripts. Hence, they form an AaORA-AaTCP15 module to synergistically activate DBR2, a crucial gene for artemisinin biosynthesis. More importantly, AaTCP15 expression is activated by the multiple reported JA and ABA-responsive TFs that promote artemisinin biosynthesis. Among them, AaGSW1 acts at the nexus of JA and ABA signalling to activate the artemisinin biosynthetic pathway and directly binds to and activates the AaTCP15 promoter apart from the AaORA promoter, which further facilitates formation of the AaGSW1-AaTCP15/AaORA regulatory module to integrate JA and ABA-mediated artemisinin biosynthesis. Our results establish a multilayer regulatory network of the AaGSW1-AaTCP15/AaORA module to regulate artemisinin biosynthesis through JA and ABA signalling, and provide an interesting avenue for future research exploring the special transcriptional regulation module of TCP genes associated with specialized metabolites in plants.


Asunto(s)
Artemisia annua , Artemisininas , Ácido Abscísico , Artemisia annua/genética , Artemisininas/metabolismo , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
18.
Rev Cardiovasc Med ; 22(4): 1535-1539, 2021 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-34957792

RESUMEN

Treatment for acute coronary syndrome (ACS) in women during pregnancy is challenging. Current standard treatment for ACS includes coronary angioplasty with guideline-directed medical therapy including aspirin, P2Y12 inhibitors, beta-blockers, angiotensin converting enzyme inhibitors, which may portend adverse effects to the fetus. ACS increases ischemic and obstetric complications during pregnancy and the postpartum period. Management of these patients necessitates balancing the potential risks and benefits to both maternal and fetal health. We present a case of a 37-year-old female with a background of hypertension and hyperlipidemia who presented with Non-ST segment elevation myocardial infarction (NSTEMI). The urine pregnancy test that was performed turned positive with an estimated gestational age of four weeks. After counselling on the potential risks and benefits, a diagnostic angiogram was performed which revealed triple vessel disease with critical stenosis in all three vessels. Percutaneous coronary intervention (PCI) was performed successfully with precautions taken to minimize radiation exposure to the fetus. In such cases, there is a fundamental trade-off between maternal and fetal health in the treatment of NSTEMI. Medications used for the treatment of acute coronary syndrome will need to be balanced against the potential risks to the fetus. Invasive coronary angiogram results in exposure to potentially teratogenic ionizing radiation and hence all efforts must be made to minimize exposure. Thus, risks and benefits of treatment ought to be discussed with patients and measures need to be taken to minimize potential harm to both the mother and fetus.


Asunto(s)
Síndrome Coronario Agudo , Angioplastia Coronaria con Balón , Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Síndrome Coronario Agudo/diagnóstico , Adulto , Angioplastia Coronaria con Balón/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Intervención Coronaria Percutánea/efectos adversos , Embarazo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia
19.
J Surg Res ; 258: 389-404, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33109405

RESUMEN

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. METHODS: The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. RESULTS: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. CONCLUSIONS: Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.


Asunto(s)
Mucosa Intestinal/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Daño por Reperfusión/metabolismo , Animales , Células Cultivadas , Mucosa Intestinal/irrigación sanguínea , Masculino , Ratones Endogámicos C57BL , Análisis por Micromatrices , Daño por Reperfusión/etiología
20.
Br J Anaesth ; 126(4): 799-807, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33342539

RESUMEN

BACKGROUND: Oliguria is often viewed as a sign of renal hypoperfusion and an indicator for volume expansion during surgery. However, the prognostic association and the predictive utility of intraoperative oliguria for postoperative acute kidney injury (AKI) are unclear. METHODS: We conducted a retrospective cohort study on patients undergoing major thoracic surgery in an academic hospital to assess the association of intraoperative oliguria with postoperative AKI and its predictive value. To contextualise our findings, we included our results in a meta-analysis of observational studies on the importance of oliguria during noncardiac surgery. RESULTS: In our cohort study, 3862 patients were included; 205 (5.3%) developed AKI after surgery. Intraoperative urine output of 0.3 ml kg-1 h-1 was the optimal threshold for oliguria in multivariable analysis. Patients with oliguria had an increased risk of AKI (adjusted odds ratio: 2.60; 95% confidence interval: 1.24-5.05). However, intraoperative oliguria had a sensitivity of 5.9%, specificity of 98%, positive likelihood ratio of 2.74, and negative likelihood ratio of 0.96, suggesting poor predictive ability. Moreover, it did not improve upon the predictive performance of a multivariable model, based on discrimination and reclassification indices. Our findings were generally consistent with the results of a systematic review and meta-analysis, including six additional studies. CONCLUSIONS: Intraoperative oliguria has moderate association with, but poor predictive ability for, postoperative AKI. It remains of clinical interest as a risk factor potentially modifiable to interventions.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Monitoreo Intraoperatorio/métodos , Oliguria/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Lesión Renal Aguda/epidemiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oliguria/epidemiología , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos
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