RESUMO
BACKGROUND: Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. METHODS: In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay. RESULTS: A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 µmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 µmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 µmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups. CONCLUSIONS: We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).
Assuntos
Injúria Renal Aguda/prevenção & controle , Estado Terminal/terapia , Solução Salina/uso terapêutico , Injúria Renal Aguda/etiologia , Adulto , Idoso , Cuidados Críticos/métodos , Estado Terminal/mortalidade , Método Duplo-Cego , Feminino , Hidratação , Gluconatos/efeitos adversos , Gluconatos/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Cloreto de Magnésio/efeitos adversos , Cloreto de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cloreto de Potássio/efeitos adversos , Cloreto de Potássio/uso terapêutico , Solução Salina/efeitos adversos , Acetato de Sódio/efeitos adversos , Acetato de Sódio/uso terapêutico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/uso terapêutico , Resultado do TratamentoRESUMO
Intravenous (i.v.) fluid therapy is critically important in pediatric kidney transplantation. Because of the high volumes given perioperatively, transplant recipients can develop significant electrolyte abnormalities depending on the types of fluids used. Current practices in pediatric transplantation aim to balance risks of hyponatremia from traditionally used hypotonic fluids, such as 0.45% sodium chloride, against hyperchloremia and acidosis associated with isotonic 0.9% sodium chloride. Using the balanced solution Plasma-Lyte 148 as an alternative might mitigate these risks.
Assuntos
Hiponatremia , Transplante de Rim , Desequilíbrio Hidroeletrolítico , Humanos , Criança , Transplante de Rim/efeitos adversos , Cloreto de Sódio/efeitos adversos , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/prevenção & controle , Hiponatremia/etiologia , Hiponatremia/prevenção & controle , EletrólitosRESUMO
Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.
Assuntos
Acidose , Hiponatremia , Transplante de Rim , Desequilíbrio Hidroeletrolítico , Humanos , Criança , Cloreto de Sódio/efeitos adversos , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Eletrólitos/efeitos adversos , Acidose/etiologia , Acidose/induzido quimicamente , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/induzido quimicamente , Hidratação/efeitos adversos , Soluções Isotônicas/efeitos adversos , Gluconatos , Cloreto de Potássio , Cloreto de Magnésio , Acetato de SódioRESUMO
Salinity poses significant challenges to agricultural productivity, impacting crops' growth, morphology and biochemical parameters. A pot experiment of three months was conducted between February to April 2023 in the Department of Botany, The Islamia University of Bahawalpur. Four brinjal (eggplant) varieties: ICS-BR-1351, HBR-313-D, HBR-314-E, and HBR-334-D were selected and assessed for the effects of salinity on various growth and biochemical attributes. The experiment was completely randomized in design with three replicates each. This study revealed that increased salinity significantly reduced the shoot length, root length, and leaf number across all varieties, with maximum adverse effects observed at a 300mM NaCl concentration. Among the tested varieties, ICS-BR-1351 demonstrated superior performance in most growth parameters, suggesting potential salt tolerance. Biochemically, salinity decreased chlorophyll content across all varieties, with the sharpest decline observed at the highest salt concentration. V4 (HBR-334-D) showed a 57% decrease in chlorophyll followed by V3 (HBR-314-E) at 56%, V2 (HBR-313-D) at 54%, and V1 (ICS-BR-1351) at 33% decrease at maximum salt levels as compared to control. Conversely, carotenoid content increased up to -42.11% in V3 followed by V2 at -81.48%, V4 at -94.11%, and - 233% in V1 at 300mM NaCl stress as compared to respective controls. V3 (HBR-314-E) has the maximum value for carotenoids while V1 has the lowest value for carotenoids as compared to the other three brinjal varieties. In addition to pigments, the study indicated a salinity-induced decrease in total proteins and total soluble sugar, whereas total amino acids and flavonoids increased. Total proteins showed a decrease in V2 (49.46%) followed by V3 (36.44%), V4 (53.42%), and V1 (53.79%) at maximum salt concentration as compared to plants treated with tap water only. Whereas, total soluble sugars showed a decrease of 52.07% in V3, 41.53% in V2, 19.49% in V1, and 18.99% in V4 at the highest salt level. While discussing total amino acid, plants showed a -9.64% increase in V1 as compared to V4 (-31.10%), V2 (-36.62%), and V3 (-22.61%) with high salt levels in comparison with controls. Plant flavonoid content increased in V3 (-15.61%), V2 (-19.03%), V4 (-18.27%) and V1 (-27.85%) at 300mM salt concentration. Notably, salinity elevated the content of anthocyanin, lycopene, malondialdehyde (MDA), and hydrogen peroxide (H2O2) across all varieties. Antioxidant enzymes like peroxidase, catalase, and superoxide dismutase also increased under salt stress, suggesting an adaptive response to combat oxidative damage. However, V3 (HBR-314-E) has shown an increase in anthocyanin at -80.00%, lycopene at -24.81%, MDA at -168.04%, hydrogen peroxide at -24.22%, POD at -10.71%, CAT as-36.63 and SOD as -99.14% at 300mM NaCl stress as compared to control and other varieties. The enhanced accumulation of antioxidants and other protective compounds suggests an adaptive mechanism in brinjal to combat salt-induced oxidative stress. The salt tolerance of different brinjal varieties was assessed by principal component analysis (PCA), and the order of salt tolerance was V1 (ICS-BR-1351) > V4 (HBR-334-D), > V2 (HBR-313-D) > V3 (HBR-314-E). Among the varieties studied, ICS-BR-1351 demonstrated resilience against saline conditions, potentially offering a promising candidate for saline-prone agricultural areas.
Assuntos
Antioxidantes , Solanum melongena , Antocianinas , Antioxidantes/metabolismo , Carotenoides , Clorofila/metabolismo , Peróxido de Hidrogênio/metabolismo , Licopeno , Salinidade , Tolerância ao Sal , Cloreto de Sódio/efeitos adversos , Solanum melongena/metabolismoRESUMO
Objectives: The high-salt diet (HSD) has been associated with cognitive dysfunction by attacking the cerebral microvasculature, through an adaptive response, initiated in the intestine and mediated by Th17 cells. In the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), it has been described that NaCl causes an increase in T cell infiltration in the central nervous system. NaCl also promotes macrophage response and Th17 cell differentiation, worsening the course of the disease. HSD may trigger an activation of the immune system and enhance inflammation. However, certain studies not only do not support this possibility, but support the opposite, as the effect of salt on immune cells may not necessarily be pathogenic. Therefore, this study aimed to evaluate the effect of an over intake of salt in rats with EAE, based on the clinical course, oxidative stress, markers of inflammation and the gut dysbiosis.Methods: 15 Dark Agouti rats were used, which were divided into control group, EAE group and EAE + NaCl group. Daily 0.027â g of NaCl dissolved in 300â µl of H2O was administered through a nasogastric tube for 51 days.Results: NaCl administration produced an improvement in clinical status and a decrease in biomarkers of oxidative stress, inflammation, and dysbiosis.Conclusion: The underlying mechanism by which NaCl causes these effects could involve the renin-angiotensin-aldosterone system (RAAS), which is blocked by high doses of salt.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Ratos , Animais , Camundongos , Esclerose Múltipla/complicações , Cloreto de Sódio/efeitos adversos , Disbiose , Inflamação/complicações , Estresse Oxidativo , Cloreto de Sódio na Dieta/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-ß1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-ß1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-ß1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-ß1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-ß1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.
Assuntos
Óxidos N-Cíclicos , Insuficiência Renal Crônica , Marcadores de Spin , Fator de Crescimento Transformador beta1 , Animais , Ratos , Albuminas/química , Albuminas/metabolismo , Peso Corporal , Colágeno/metabolismo , Creatinina , Dieta , Fibrose , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Nefrectomia , NF-kappa B/metabolismo , Estresse Oxidativo , Insuficiência Renal Crônica/tratamento farmacológico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Biomarcadores , Sódio na Dieta/efeitos adversosRESUMO
Dr Irvine Page proposed the Mosaic Theory of Hypertension in the 1940s advocating that hypertension is the result of many factors that interact to raise blood pressure and cause end-organ damage. Over the years, Dr Page modified his paradigm, and new concepts regarding oxidative stress, inflammation, genetics, sodium homeostasis, and the microbiome have arisen that allow further refinements of the Mosaic Theory. A constant feature of this approach to understanding hypertension is that the various nodes are interdependent and that these almost certainly vary between experimental models and between individuals with hypertension. This review discusses these new concepts and provides an introduction to other reviews in this compendium of Circulation Research.
Assuntos
Hipertensão/fisiopatologia , Aldosterona/fisiologia , Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Vasos Sanguíneos/fisiologia , Líquidos Corporais/fisiologia , Sistema Nervoso Central/fisiologia , Humanos , Hipertensão/etiologia , Inflamação/complicações , Rim/fisiologia , Microbiota/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Risco , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/efeitos adversos , Vasoconstritores/farmacologiaRESUMO
BACKGROUND: Anthocyanin plays a protective role in cardiovascular disease through antioxidant effect. Whether anthocyanin can reduce salt-induced hypertension and the related mechanisms remain unclear. METHODS: Chronic infusion of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL/h) or anthocyanin (10 mg/kg, 0.4 µL/h) into bilateral paraventricular nucleus (PVN) of Sprague-Dawley rats was performed. Then, the rats were fed a high salt diet (8% NaCl, HS) or normal salt diet (0.9%, NaCl, NS) for 4 weeks. RESULTS: High salt diet induced an increase in blood pressure and peripheral sympathetic nerve activity (increased LF/HF and decreased SDNN and RMSSD), which was accompanied by increased reactive oxygen species (ROS) production and angiotensin II type-1 receptor (AT1R) expression and function in the PVN. Moreover, the NOD-like receptor protein 3 (NLRP3) and related inflammatory proteins (caspase-1) expression, the pro-inflammatory cytokine levels including IL-1ß and TNF-α were higher in PVN of rats with a high salt diet. Bilateral PVN infusion of anthocyanin attenuated NLRP3-dependent inflammation (NLRP3, caspase-1, IL-1ß and TNF-α) and ROS production, reduced AT1R expression and function in PVN and lowered peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension. CONCLUSIONS: Excessive salt intake activates NLRP3-dependent inflammation and oxidative stress and increased AT1R expression and function in the PVN. Bilateral PVN infusion of anthocyanin lowers peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension by improvement of expression and function of AT1R in the PVN through inhibiting NLRP3 related inflammatory and oxidative stress.
Assuntos
Antocianinas , Hipertensão , Ratos , Animais , Antocianinas/efeitos adversos , Antocianinas/metabolismo , Cloreto de Sódio na Dieta/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Sistema Nervoso Simpático , Inflamação/metabolismo , Caspases/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismoRESUMO
Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type â collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type â ¢ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen â , collagen â ¢, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type â collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) µg/mg vs. (0.974±0.060) µg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type â collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) µg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type â collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type â ¢ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type â collagen, type â ¢ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type â ¢ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type â collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type â ¢ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type â ¢ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type â ¢ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.
Assuntos
Canabinoides , Fibrose Pulmonar , Camundongos , Masculino , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Agonistas de Receptores de Canabinoides/efeitos adversos , Agonistas de Receptores de Canabinoides/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , Colágeno Tipo III/metabolismo , Colágeno Tipo III/farmacologia , Hidroxiprolina/análise , Hidroxiprolina/metabolismo , Hidroxiprolina/farmacologia , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/patologia , Canabinoides/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/metabolismo , Colágeno/efeitos adversos , Colágeno/metabolismo , Inflamação/patologia , RNA Mensageiro/metabolismoRESUMO
A high salt (HS) diet is associated with an increased risk for cardiovascular diseases (CVDs) and fibrosis is a key contributor to the organ dysfunction involved in CVDs. The activation of the renin angiotensin type 2 receptor (AT2R) has been considered as organ protective in many CVDs. However, there are limited AT2R-selective agonists available. Our first reported ß-substituted angiotensin III peptide, ß-Pro7-AngIII, showed high selectivity for the AT2R. In the current study, we examine the potential anti-fibrotic and anti-inflammatory effects of this novel AT2R-selective peptide on HS-induced organ damage. FVB/N mice fed with a 5% HS diet for 8 weeks developed cardiac and renal fibrosis and inflammation, which were associated with increased TGF-ß1 levels in heart, kidney and plasma. Four weeks' treatment (from weeks 5-8) with ß-Pro7-AngIII inhibited the HS-induced cardiac and renal fibrosis and inflammation. These protective effects were accompanied by reduced local and systemic TGF-ß1 as well as reduced cardiac myofibroblast differentiation. Importantly, the anti-fibrotic and anti-inflammatory effects caused by ß-Pro7-AngIII were attenuated by the AT2R antagonist PD123319. These results demonstrate, for the first time, the cardio- and reno-protective roles of the AT2R-selective ß-Pro7-AngIII, highlighting it as an important therapeutic that can target the AT2R to treat end-organ damage.
Assuntos
Nefropatias , Fator de Crescimento Transformador beta1 , Animais , Camundongos , Fator de Crescimento Transformador beta1/efeitos adversos , Fibrose , Nefropatias/etiologia , Nefropatias/induzido quimicamente , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio/efeitos adversos , Inflamação , Anti-Inflamatórios/efeitos adversosRESUMO
BACKGROUND: Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients. METHODS: This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups. RESULTS: In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries. CONCLUSIONS: Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.
Assuntos
Arritmias Cardíacas/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Soluções Cardioplégicas/uso terapêutico , Ponte Cardiopulmonar/efeitos adversos , Eletrólitos/uso terapêutico , Parada Cardíaca Induzida , Lidocaína/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Manitol/uso terapêutico , Cloreto de Potássio/uso terapêutico , Bicarbonato de Sódio/uso terapêutico , Soluções/uso terapêutico , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Bicarbonatos/efeitos adversos , Bicarbonatos/uso terapêutico , Cloreto de Cálcio/efeitos adversos , Cloreto de Cálcio/uso terapêutico , Soluções Cardioplégicas/efeitos adversos , China/epidemiologia , Eletrólitos/efeitos adversos , Feminino , Parada Cardíaca Induzida/efeitos adversos , Humanos , Incidência , Unidades de Terapia Intensiva , Tempo de Internação , Lidocaína/efeitos adversos , Magnésio/efeitos adversos , Magnésio/uso terapêutico , Sulfato de Magnésio/efeitos adversos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Cloreto de Potássio/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Bicarbonato de Sódio/efeitos adversos , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/uso terapêutico , Soluções/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.
Assuntos
Diterpenos/uso terapêutico , Ventrículos do Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Cloreto de Sódio/efeitos adversos , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Ecocardiografia , Hipertensão/induzido quimicamente , Hipertensão/imunologia , Hipertensão/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Fenótipo , Células RAW 264.7 , Remodelação Ventricular/imunologiaRESUMO
Moderation in the use of salt (sodium chloride) in food and food preparations prevents the tendency of blood pressure to increase with age, and this is documented by many studies in current literature [...].
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Dieta Hipossódica/tendências , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio/efeitos adversos , Pressão Sanguínea/fisiologia , Dieta/métodos , Dieta/tendências , Dieta Hipossódica/métodos , Humanos , Hipertensão/fisiopatologia , Cloreto de Sódio/metabolismoRESUMO
Salt stress negatively affects maize growth and yield. Application of plant growth regulator is an effective way to improve crop salt tolerance, therefore reducing yield loss by salt stress. Here, we used a novel plant growth regulator B2, which is a functional analogue of ABA. With the aim to determine whether B2 alleviates salt stress on maize, we studied its function under hydroponic conditions. When the second leaf was fully developed, it was pretreated with 100 µM ABA, 0.01 µM B2, 0.1 µM B2, and 1 µM B2, independently. After 5 days treatment, NaCl was added into the nutrient solution for salt stress. Our results showed that B2 could enhance salt tolerance in maize, especially when the concentration was 1.0 µMol·L-1. Exogenous application of B2 significantly enhanced root growth, and the root/shoot ratio increased by 7.6% after 6 days treatment under salt stress. Compared with control, the ABA level also decreased by 31% after 6 days, which might have resulted in the root development. What is more, B2 maintained higher photosynthetic capacity in maize leaves under salt stress conditions and increased the activity of antioxidant enzymes and decreased the generation rate of reactive oxygen species by 16.48%. On the other hand, B2 can enhance its water absorption ability by increasing the expression of aquaporin genes ZmPIP1-1 and ZmPIP1-5. In conclusion, the novel plant growth regulator B2 can effectively improve the salt tolerance in maize.
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Ácido Abscísico/análogos & derivados , Ácido Abscísico/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/crescimento & desenvolvimento , Tolerância ao Sal/fisiologia , Zea mays/crescimento & desenvolvimento , Aquaporinas/biossíntese , Aquaporinas/genética , Raízes de Plantas/metabolismo , Salinidade , Estresse Salino/efeitos dos fármacos , Plântula/metabolismo , Cloreto de Sódio/efeitos adversos , Zea mays/metabolismoRESUMO
Their high adaptability to difficult coastal conditions makes mangrove trees a valuable resource and an interesting model system for understanding the molecular mechanisms underlying stress tolerance and adaptation of plants to the stressful environmental conditions. In this study, we used RNA sequencing (RNA-Seq) for de novo assembling and characterizing the Bruguiera gymnorhiza (L.) Lamk leaf transcriptome. B. gymnorhiza is one of the most widely distributed mangrove species from the biggest family of mangroves; Rhizophoraceae. The de novo assembly was followed by functional annotations and identification of individual transcripts and gene families that are involved in abiotic stress response. We then compared the genome-wide expression profiles between two populations of B. gymnorhiza, growing under different levels of stress, in their natural habitats. One population living in high salinity environment, in the shore of the Pacific Ocean- Japan, and the other population living about one kilometre farther from the ocean, and next to the estuary of a river; in less saline and more brackish condition. Many genes involved in response to salt and osmotic stress, showed elevated expression levels in trees growing next to the ocean in high salinity condition. Validation of these genes may contribute to future salt-resistance research in mangroves and other woody plants. Furthermore, the sequences and transcriptome data provided in this study are valuable scientific resources for future comparative transcriptome research in plants growing under stressful conditions.
Assuntos
Pressão Osmótica/efeitos dos fármacos , Rhizophoraceae/genética , Estresse Fisiológico/genética , Transcriptoma/genética , Adaptação Fisiológica/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Anotação de Sequência Molecular , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Rhizophoraceae/crescimento & desenvolvimento , Salinidade , Tolerância ao Sal/genética , Cloreto de Sódio/efeitos adversos , ÁrvoresRESUMO
Seed-borne endophyte Epichloë gansuensis enhance NaCl tolerance in Achnatherum inebrians and increase its biomass. However, the molecular mechanism by which E. gansuensis increases the tolerance of host grasses to NaCl stress is unclear. Hence, we firstly explored the full-length transcriptome information of A. inebrians by PacBio RS II. In this work, we obtained 738,588 full-length non-chimeric reads, 36,105 transcript sequences and 27,202 complete CDSs from A. inebrians. We identified 3558 transcription factors (TFs), 15,945 simple sequence repeats and 963 long non-coding RNAs of A. inebrians. The present results show that 2464 and 1817 genes were differentially expressed by E. gansuensis in the leaves of E+ and E- plants at 0 mM and 200 mM NaCl concentrations, respectively. In addition, NaCl stress significantly regulated 4919 DEGs and 502 DEGs in the leaves of E+ and E- plants, respectively. Transcripts associated with photosynthesis, plant hormone signal transduction, amino acids metabolism, flavonoid biosynthetic process and WRKY TFs were differentially expressed by E. gansuensis; importantly, E. gansuensis up-regulated biology processes (brassinosteroid biosynthesis, oxidation-reduction, cellular calcium ion homeostasis, carotene biosynthesis, positive regulation of proteasomal ubiquitin-dependent protein catabolism and proanthocyanidin biosynthesis) of host grass under NaCl stress, which indicated an increase in the ability of host grasses' adaptation to NaCl stress. In conclusion, our study demonstrates the molecular mechanism for E. gansuensis to increase the tolerance to salt stress in the host, which provides a theoretical basis for the molecular breed to create salt-tolerant forage with endophytes.
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Epichloe/fisiologia , Perfilação da Expressão Gênica/métodos , Poaceae/crescimento & desenvolvimento , RNA Longo não Codificante/genética , Estresse Salino , Fatores de Transcrição/genética , Endófitos/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Fotossíntese , Filogenia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/microbiologia , Proteínas de Plantas/genética , Poaceae/genética , Poaceae/microbiologia , RNA de Plantas/genética , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/microbiologia , Cloreto de Sódio/efeitos adversos , Sequenciamento do ExomaRESUMO
Thompson Seedless, a commonly grown table grape variety, is sensitive to salinity when grown on its own roots, and therefore, it is frequently grafted onto salinity-tolerant wild grapevine rootstocks. Rising soil salinity is a growing concern in irrigated agricultural systems. The accumulation of salts near the root zone severely hampers plant growth, leading to a decrease in the productive lifespan of grapevine and causing heavy yield losses to the farmer. In the present study, we investigated the differences in response to salinity between own-rooted Thompson Seedless (TSOR) and 110R-grafted Thompson Seedless (TS110R) grapevines, wherein 110R is reported to be a salt-tolerant rootstock. The grapevines were subjected to salt stress by treating them with a 150 mM NaCl solution. The stress-induced changes in protein abundance were investigated using a label-free shotgun proteomics approach at three time-points viz. 6 h, 48 h, and 7 days of salt treatment. A total of 2793 proteins were identified, of which 246 were differentially abundant at various time-points in TSOR and TS110R vines. The abundance of proteins involved in several biological processes such as photosynthesis, amino acid metabolism, translation, chlorophyll biosynthesis, and generation of precursor metabolites was significantly affected by salt stress in both the vines but at different stages of stress. The results revealed that TSOR vines responded fervently to salt stress, while TS110R vines adopted a preventive approach. The findings of this study add to the knowledge of salinity response in woody and grafted plants and hence open the scope for further studies on salt stress-specific differences induced by grafting.
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Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Estresse Salino , Vitis/metabolismo , Cromatografia Líquida/métodos , Regulação da Expressão Gênica de Plantas/fisiologia , Ontologia Genética , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Raízes de Plantas/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Salinidade , Estresse Salino/fisiologia , Cloreto de Sódio/efeitos adversos , Espectrometria de Massas em Tandem/métodos , Vitis/efeitos adversos , Vitis/fisiologiaRESUMO
This review will highlight recent studies that have investigated the relationship between Na+, renal macrophage polarization, and renal damage. A hyperosmotic environment drives the macrophage toward a proinflammatory phenotype and away from an anti-inflammatory phenotype. Animal models of salt-sensitive hypertension demonstrate a characteristic infiltration of macrophages into the kidney that is greatly reduced when blood pressure is lowered. Because general immunosuppression or macrophage depletion leads to a host of adverse side effects, more recent studies have modulated the interaction of specific signaling molecules, including NOD-like receptor family pyrin domain-containing 3, chemokine (C-X-C motif) ligand 16, and VEGF, to prevent the end-organ renal damage that accumulates in salt-sensitive disease.
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Hipertensão/patologia , Inflamação/metabolismo , Nefropatias/patologia , Rim/metabolismo , Macrófagos/metabolismo , Cloreto de Sódio/efeitos adversos , Animais , HumanosRESUMO
MAIN CONCLUSION: To compensate for the lack of capacity for external salt storage in the epidermal bladder cells, quinoa plants employ tissue-tolerance traits, to confer salinity stress tolerance. Our previous studies indicated that sequestration of toxic Na+ and Cl- ions into epidermal bladder cells (EBCs) is an efficient mechanism conferring salinity tolerance in quinoa. However, some halophytes do not develop EBCs but still possess superior salinity tolerance. To elucidate the possible compensation mechanism(s) underlying superior salinity tolerance in the absence of the external salt storage capacity, we have selected four quinoa accessions with contrasting patterns of EBC development. Whole-plant physiological and electrophysiological characteristics were assessed after 2 days and 3 weeks of 400 mM NaCl stress. Both accessions with low EBC volume utilised Na+ exclusion at the root level and could maintain low Na+ concentration in leaves to compensate for the inability to sequester Na+ load in EBC. These conclusions were further confirmed by electrophysiological experiments showing higher Na+ efflux from roots of these varieties (measured by a non-invasive microelectrode MIFE technique) as compared to accessions with high EBC volume. Furthermore, accessions with low EBC volume had significantly higher K+ concentration in their leaves upon long-term salinity exposures compared to plants with high EBC sequestration ability, suggesting that the ability to maintain high K+ content in the leaf mesophyll was as another important compensation mechanism.
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Chenopodium quinoa/fisiologia , Cloreto de Sódio/efeitos adversos , Chenopodium quinoa/crescimento & desenvolvimento , Íons/metabolismo , Fenótipo , Desenvolvimento Vegetal , Epiderme Vegetal/crescimento & desenvolvimento , Epiderme Vegetal/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Salinidade , Tolerância ao Sal , Plantas Tolerantes a Sal , Estresse FisiológicoRESUMO
Listeria monocytogenes causes the severe foodborne illness listeriosis and survives in food-associated environments due to its high stress tolerance. A data assembly and analysis protocol for microbial growth experiments was compiled to elucidate the strain variability of L. monocytogenes stress tolerance. The protocol includes measurement of growth ability under stress (step 1), selection of a suitable method for growth parameter calculation (step 2), comparison of growth patterns between strains (step 3), and biological interpretation of the discovered differences (step 4). In step 1, L. monocytogenes strains (n = 388) of various serovars and origins grown on media with 9.0% NaCl were measured using a Bioscreen C microbiology reader. Technical variability of the growth measurements was assessed and eliminated. In step 2, the growth parameters determined by Gompertz, modified-Gompertz, logistic, and Richards models and model-free splines were compared, illustrating differences in the suitability of these methods to describe the experimental data. In step 3, hierarchical clustering was used to describe the NaCl tolerance of L. monocytogenes measured by strain-specific variation in growth ability; tolerant strains had higher growth rates and maximum optical densities and shorter lag phases than susceptible strains. The spline parameter area under the curve best classified "poor," "average," and "good" growers. In step 4, the tested L. monocytogenes lineage I strains (serovars 4b and 1/2b) proved to be significantly more tolerant toward 9.0% NaCl than lineage II strains (serovars 1/2a, 1/2c, and 3a). Our protocol provides systematic tools to gain comparable data for investigating strain-specific variation of bacterial growth under stress.IMPORTANCE The pathogen Listeria monocytogenes causes the foodborne disease listeriosis, which can be fatal in immunocompromised individuals. L. monocytogenes tolerates several environmental stressors and can persist in food-processing environments and grow in foodstuffs despite traditional control measures such as high salt content. Nonetheless, L. monocytogenes strains differ in their ability to withstand stressors. Elucidating the intraspecies strain variability of L. monocytogenes stress tolerance is crucial for the identification of particularly tolerant strains. To enhance reliable identification of variability in bacterial stress tolerance phenotypes, we compiled a large-scale protocol for the entire data assembly and analysis of microbial growth experiments, providing a systematic approach and checklist for experiments on strain-specific growth ability. Our study illustrated the diversity and strain-specific variation of L. monocytogenes stress tolerance with an unprecedented scope and discovered biologically relevant serovar- and lineage-dependent phenotypes of NaCl tolerance.