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1.
J Pers Med ; 10(4)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066497

RESUMO

miR-22 is one of the most abundant miRNAs in the liver and alterations of its hepatic expression have been associated with the development of hepatic steatosis and insulin resistance, as well as cancer. However, the pathophysiological roles of miR-22-3p in the deregulated hepatic metabolism with obesity and cancer remains poorly characterized. Herein, we observed that alterations of hepatic miR-22-3p expression with non-alcoholic fatty liver disease (NAFLD) in the context of obesity are not consistent in various human cohorts and animal models in contrast to the well-characterized miR-22-3p downregulation observed in hepatic cancers. To unravel the role of miR-22 in obesity-associated NAFLD, we generated constitutive Mir22 knockout (miR-22KO) mice, which were subsequently rendered obese by feeding with fat-enriched diet. Functional NAFLD- and obesity-associated metabolic parameters were then analyzed. Insights about the role of miR-22 in NAFLD associated with obesity were further obtained through an unbiased proteomic analysis of miR-22KO livers from obese mice. Metabolic processes governed by miR-22 were finally investigated in hepatic transformed cancer cells. Deletion of Mir22 was asymptomatic when mice were bred under standard conditions, except for an onset of glucose intolerance. However, when challenged with a high fat-containing diet, Mir22 deficiency dramatically exacerbated fat mass gain, hepatomegaly, and liver steatosis in mice. Analyses of explanted white adipose tissue revealed increased lipid synthesis, whereas mass spectrometry analysis of the liver proteome indicated that Mir22 deletion promotes hepatic upregulation of key enzymes in glycolysis and lipid uptake. Surprisingly, expression of miR-22-3p in Huh7 hepatic cancer cells triggers, in contrast to our in vivo observations, a clear induction of a Warburg effect with an increased glycolysis and an inhibited mitochondrial respiration. Together, our study indicates that miR-22-3p is a master regulator of the lipid and glucose metabolism with differential effects in specific organs and in transformed hepatic cancer cells, as compared to non-tumoral tissue.

2.
Front Immunol ; 11: 566535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101287

RESUMO

The macrophage-to-myofibroblast transition (MMT) process is an important pathway that contributing to renal interstitial fibrosis (RIF). Fatty acid-binding protein 4 (FABP4) deteriorated RIF via promoting inflammation in obstructive nephropathy. However, the clinical significance of FABP4 in fibrotic kidney disease remains to be determined and little is known of the FABP4 signaling in MMT. Biopsy specimens of chronic kidney disease patients and kidneys subjected to unilateral ureteral obstruction (UUO) of FABP4-deficient mice or FABP4 inhibitor-treated mice were collected for the investigation of FABP4 mediating MMT of RIF. We conducted kidney RNA-seq transcriptomes and TGF-ß1-induced bone marrow-derived macrophage (BMDM) assays to determine the mechanisms of FABP4. We found that FABP4 expression correlated with RIF in biopsy specimens and the injured kidneys of UUO mice where FABP4 was co-expressed with MMT cells. In UUO mice, FABP4 deficiency and a highly selective FABP4 inhibitor BMS309403 treatment both suppressed RIF. FABP4 ablation also attenuated the UUO-induced number of MMT cells and serum amyloid A1 (Saa1) expression. The siRNA-mediated Saa1 knockdown decreased the number of MMT cells in vitro. In conclusion, FABP4 is an important factor contributing to RIF by mediating MMT, and genetic/pharmacological inhibition of FABP4 provides a novel approach for the treatment of kidney fibrosis.

3.
Curr Med Chem ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081669

RESUMO

Mitochondria are potent source of cellular reactive oxygen species (ROS) and are vulnerable to oxidative damage. Mitochondria dysfunction could result in adenosine triphosphate (ATP) decrease and cell death. The kidney is an ATPconsuming organ, and the relationship between mitochondrial dysfunction and renal disease has been long noted. Mitochondrial targeting is a novel strategy for kidney diseases. At present, there are several ways to target mitochondria such as the addition of a triphenylphosphonium cation, mitochondria-targeted peptides, and nanocarrier. There are also a variety of choices for the payload, such as nitroxides, quinone derivates, vitamins and so on. This review summarized chemical and also clinical characteristics of various mitochondria-targeted antioxidants and focused on their application and perspectives in kidney diseases.

4.
Int J Artif Organs ; : 391398820962112, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016167

RESUMO

OBJECTIVES: Examine the impacts of age, diabetes, gender, and access type on vascular access (VA) associated costs among Chinese hemodialysis (HD) patients. METHODS: We retrospectively included patients whose first permanent VA was created at the West China Hospital. Clinical characteristics, maturation, intervention, utilization, and exchange of every VA, as well as VA-related infection were collected. The study period for each patient was from HD initiation to the last follow-up. VA-related costs, including those for placement and intervention procedures, were calculated according to the standards set in 2019 for Chinese tertiary hospitals. Mann-Whitney U and Chi-square tests were conducted for comparisons between groups. RESULTS: A total of 358 Chinese HD patients experienced functionally 143 arteriovenous fistula (AVF), 22 arteriovenous graft (AVG), and 439 tunneled cuffed central venous catheter (tcCVC) during a median study period of 26 (IQR 13-44) months, of which 42.5% used more than one permanent VA. The median annual VA-related cost in the groups of age >75 years and ⩽75 years, diabetes and non-diabetes, male and female, was $525 and $397 (p = 0.016), $459 and $462 (p = 0.64), $476 and $445 (p = 0.94), respectively. The median monthly costs for AVF ($18), AVG ($289), and tcCVC ($37) were significantly different. CONCLUSION: HD patients aged >75 years had significantly higher annual VA-related costs. However, the annual VA-related costs did not differ across the diabetes groups or the gender groups. AVF was the most cost-effective permanent VA type in China, partly due to the inexpensive materials used compared to AVG or tcCVC.

5.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(6): 850-855, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895208

RESUMO

OBJECTIVE: To investigate the effects of Shoutai pills (a traditional Chinese medicinal preparation) on immune functions and oxidative stress in pregnant rats exposed to di(2-ethylhexyl) phthalate (DEHP). METHODS: Thirty-six mature female SD rats were randomly divided into 3 groups (n=12). After pregnancy was confirmed, the rats were given 10 mL/kg corn oil +10 mL/kg saline (control group), 500 mg/kg DEHP+10 mL/kg saline (model group), and 500 mg/kg DEHP+10 mL/kg Shoutai pills (treatment group). At 19 days of gestation, the rats were sacrificed and the fetal rats were weighed and the numbers of live and stillborn fetal rats were recorded. Serum levels of interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor-ɑ (TNF-ɑ), estradiol (E2) and progesterone (P) levels were detected. The appearance, color and quality of the placenta in each group were recorded, and the placental tissues were examined pathologically. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH- Px), catalase (CAT), reactive oxygen species (ROS) and malondialdehyde (MDA) in the placental tissues were measured. RESULTS: Compared with the control group, the rats with DEHP exposure showed slow weight gain in the middle and late gestation period and significantly lower fetal weight (P < 0.05) with lowered serum levels of IL-2, IL-6 and TNF-ɑ, increased estradiol level (P < 0.05), decreased placental T-AOC, GSH-Px, SOD and CAT levels, and increased ROS and MDA levels (P < 0.01). Compared with the model group, the rats treated with Shoutai pills had significantly increased weight gain in mid and late pregnancy and greater fetal weight (P < 0.05) with significantly increased serum IL-2 and IL-6 levels, decreased estradiol level (P < 0.05), slightly increased TNF-ɑ expression (P> 0.05), increased placenta T-AOC, GSH- Px and CAT levels, decreased MDA level (P < 0.05), and slightly increased SOD and decreased ROS levels (P>0.05). No significant difference was found in progesterone levels among the groups (P>0.05). HE staining showed that the trophoblast in the placental tissue sponge in the model group was loose and irregular with numerous vacuoles. In the treatment group, the structure of the placenta remained intact with clearly visible labyrinth zone, sponge trophoblast and giant cell trophoblast, and the cell distribution in each layer was better than that in the model group. CONCLUSIONS: Shoutai pills can regulate the immune function of DEHP-exposed pregnant rats possibly by antagonizing the estrogenlike effect of DEHP and regulating serum immune factors; Shoutai pills can also reduce placental tissue damage and improve pregnancy outcome by correcting DEHP-induced imbalance of oxidative stress in the placental tissues.


Assuntos
Estresse Oxidativo , Animais , Dietilexilftalato , Feminino , Ácidos Ftálicos , Gravidez , Ratos , Ratos Sprague-Dawley
6.
J Ovarian Res ; 13(1): 106, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32921318

RESUMO

The exact pathogenesis of polycystic ovary syndrome (PCOS), the most common neuroendocrine disorder in women of reproductive age, has not been fully elucidated. Recent studies suggested that chronic inflammation and neurotransmitter disorder involved in the progress of PCOS. Troxerutin, a natural flavonoid, was reported to possess neuroprotective effect in several disease models by inhibiting inflammation or enhancing neurotrophic factor. In this study, we investigated the possible protective effect and mechanism of troxerutin in a dihydrotestosterone (DHT)-induced rat model of PCOS. The PCOS rat models were treated with troxerutin at a dose of 150 mg/kg or 300 mg/kg for up to 4 weeks. Results showed that 300 mg/kg troxerutin significantly decreased the body weight gain and improved the pathological changes of ovary induced by DHT. Meanwhile, the elevated gonadotrophin-releasing hormone (GnRH), gonadotrophin and testosterone in the serum of PCOS rats were reduced with the treatment of troxerutin. The expression of kisspeptin and NKB in arcuate nucleus and their receptors kiss1r and NK3r in GnRH positive neurons of median eminence were markedly decreased in troxerutin-treated rats. Of note, the GnRH inhibitory regulator GABA and stimulatory regulator glutamate were also restored to the normal level by troxerutin. The present study indicated that troxerutin may exhibit a protective effect in PCOS rat model via regulating neurotransmitter release.

7.
Acta Pharmacol Sin ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948825

RESUMO

Diabetic nephropathy (DN) is one of the most common causes of end-stage renal disease worldwide. ω3-Fatty acids (ω3FAs) were found to attenuate kidney inflammation, glomerulosclerosis, and albuminuria in experimental and clinical studies of DN. As G protein-coupled receptor 120 (GPR120) was firstly identified as the receptor of ω3FAs, we here investigated the function of GPR120 in DN. We first examined the renal biopsies of DN patients, and found that GPR120 expression was negatively correlated with the progression of DN. Immunofluorescence staining analysis revealed that GPR120 protein was mainly located in the podocytes of the glomerulus. A potent and selective GPR120 agonist TUG-891 (35 mg · kg-1 · d-1, ig) was administered to db/db mice for 4 weeks. We showed that TUG-891 administration significantly improved urinary albumin excretion, protected against podocyte injury, and reduced collagen deposition in the glomerulus. In db/db mice, TUG-891 administration significantly inhibited the mRNA and protein expression of fibronectin, collagen IV, α-SMA, TGF-ß1, and IL-6, and downregulated the phosphorylation of Smad3 and STAT3 to alleviate glomerulosclerosis. Similar results were observed in high-glucose-treated MPC5 podocytes in the presence of TUG-891 (10 µM). Furthermore, we showed that TUG-891 effectively upregulated GPR120 expression, and suppressed TAK1-binding protein-1 expression as well as the phosphorylation of TAK1, IKKß, NF-κB p65, JNK, and p38 MAPK in db/db mice and high-glucose-treated MPC5 podocytes. Knockdown of GPR120 in MPC5 podocytes caused the opposite effects of TUG-891. In summary, our results highlight that activation of GPR120 in podocytes ameliorates renal inflammation and fibrosis to protect against DN.

8.
Phlebology ; : 268355520955090, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928071

RESUMO

The objective is to compare Multi-detector CT angiography (MDCTA) and digital subtraction angiography (DSA) in diagnosing hemodialysis catheter related-central venous stenosis (CVS). During a period of 6 years, hemodialysis patients with suspected catheter related-CVS who received both MDCTA and DSA were retrospectively enrolled. We analyzed the sensitivity, specificity, accuracy, Cohen's kappa coefficient (κ) and other diagnostic parameters for MDCTA compared to DSA. A total of 1533 vascular segments in 219 patients were analyzed. Among the 280 lesions identified by DSA, 156 were correctly identified by MDCTA. There were 124 false negative and 41 false positive diagnoses. MDCTA had a high specificity (96.73%) but a low sensitivity (55.71%), with a moderate inter-test agreement (κ = 0.5930). In stratified analyses of vascular segments, the specificities of MDCTA were 89.93% (superior vena cava), 98.95% (left brachiocephalic vein), 95.33% (right brachiocephalic vein), 99.53% (left subclavian vein), 97.61% (right subclavian vein), 97.13% (left internal jugular vein), and 95.86% (right internal jugular vein), while the sensitivities were 90.00%, 65.52%, 66.67%, 87.50%, 40.00%, 20.00% and 8.11%, respectively. Good to excellent inter-test agreement was observed for the superior vena cava (κ = 0.7870), left brachiocephalic vein (κ = 0.7300), right brachiocephalic vein (κ = 0.6610), and left subclavian vein (κ = 0.8700) compared with poor to low agreement for the right subclavian vein (κ = 0.3950), left internal jugular vein (κ = 0.1890), and right internal jugular vein (κ = 0.0500). MDCTA had a high specificity in diagnosing hemodialysis catheter related-CVS. Its sensitivity varied by central venous segments, with better performance in superior vena cava and brachiocephalic veins.

9.
Eur J Pharmacol ; 887: 173570, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32949603

RESUMO

Hyperuricemia is an independent risk factor for chronic kidney disease (CKD). Excessive uric acid (UA) level in the blood leads to hyperuricemic nephropathy (HN), which is characterized by glomerular hypertension, arteriolosclerosis and tubulointerstitial fibrosis. Fatty acid binding protein 4 (FABP4) is a potential mediator of inflammatory responses which contributes to renal interstitial fibrosis. However, the roles of FABP4 in HN remains unknown. In the study, a mouse model of HN induced by feeding a mixture of adenine and potassium oxonate, severe kidney injury and interstitial fibrosis, as well as the increased kidney-expressed FABP4 protein level were evident, accompanied by the activation of inflammatory responses. Oral administration of BMS309403, a highly selective FABP4 inhibitor, improved renal dysfunction, inhibited the mRNA level of KIM-1 and NGAL, as well as reduced the expression of proinflammatory cytokines and fibrotic proteins in the injured kidneys. BMS309403 treatment also inhibited the FABP4 activity and further suppressed the activation of JAK2-STAT3 and NF-kB P65 signaling pathways in the hyperuricemia-injured kidneys and UA-stimulated human tubular epithelial (HK-2) cells, respectively. In summary, our study for the first time demonstrated that FABP4 played a crucial role in kidney inflammation and fibrosis via the regulation of JAK2-STAT3 and NF-kB P65 pathways in HN mice. The results suggested that FABP4 inhibition might be a promising therapeutic strategy for HN.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32805894

RESUMO

In order to improve the thermoelectric properties of single-walled carbon nanotubes (SWCNTs), bilayer-like structures of graphene quantum dots (GQDs) and SWCNTs films (b-GQDs/SWCNTs) were prepared by directly coating GQDs on the surface of SWCNTs films. Compared to pristine SWCNT films (p-SWCNTs), the electrical conductivity of b-GQDs/SWCNTs increased while their Seebeck coefficient decreased. The special interface structure of GQDs and SWCNTs can not only improve carrier transport to increase electrical conductivity but also scatter phonons to reduce thermal conductivity. A maximum power factor (PF) of 51.2 µW·m-1·K-2 is obtained at 298 K for the b-GQDs/SWCNTs (2:100), which is higher than the PF of 40.9 µW·m-1·K-2 by p-SWCNTs. Incorporation of GQDs shows an obvious improvement in power factor and a significant reduction in the thermal conductivity for SWCNTs, and thus, preparation of b-GQDs/SWCNTs provides a new strategy to enhance the thermoelectric properties of SWCNTs-based materials.

11.
J Ethnopharmacol ; 264: 113278, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32841699

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liriodendron chinense (Hemsl.) Sarg, known as the Chinese tulip tree, has a long history of cultivation and utilization in many Asia countries, especially in China to use in traditional Chinese medicine for expelling "wind and dampness", a term corresponding to rheumatic fever and rheumatoid arthritis. Interestingly, the barks of Liriodendron chinense (Hemsl.) Sarg was also found in folk to treat gout. However, further experimental studies remained to confirm its uric acid-lowering effects. AIM OF THE STUDY: The aim of the study was to evaluate the protective effect of ethanol extract of the barks of Liriodendron chinense (Hemsl.) Sarg (EELC) in a mouse model of hyperuricemic nephropathy (HN) and the involved mechanisms. MATERIALS AND METHODS: EELC at a respective dose of 250 mg/kg/d or 500 mg/kg/d were orally administered to HN mice induced by a mixture of adenine (160 mg/kg/d)/potassium oxonate (2.4 g/kg/d) for 21 days. At the end of the treatment, serum uric acid, kidney functions (serum creatinine, blood urea nitrogen and urine microalbumin), 24-h urine uric acid excretion, as well as kidney pathological changes were investigated by biochemical assay, histopathological score, immunofluorescence and histochemistry, RT-qPCR, and western blotting analysis. RESULTS AND DISCUSSION: Oral administration of EELC significantly lowered serum uric acid level at 500 mg/kg (185.75 ± 15.49 µmol/L of EELC vs. 238.28 ± 20.97 µmol/L of HN model, p < 0.01) in HN mice. EELC at 500 mg/kg also remarkably reduced the levels of serum creatinine (82.92 ± 7.86 µmol/L of EELC vs. 92.08 ± 6.13 µmol/L of HN model, p < 0.0001), blood urea nitrogen (21.50 ± 1.87 mmol/L of EELC vs. 29.40 ± 3.95 mmol/L of HN model, p < 0.001) and urine microalbumin (4.25 ± 0.40 mg/L of EELC vs. 5.95 ± 0.33 mg/L of HN model, p < 0.001) to improve renal function. It also attenuated renal fibrosis, especially the high-dose of EELC. Furthermore, EELC could inhibit the activation of NF-κB, ASK1/JNK/c-Jun, JAK2/STAT3 signaling pathways and reduce the release of pro-inflammatory cytokine TNF-α in the kidneys of HN mice. Additionally, EELC remarkably increased urine uric acid excretion of HN mice, which may be achieved by the upregulation of organic anion transporter 1 (OAT1), OAT3 and ATP-binding cassette subfamily G member 2 (ABCG2) proteins. CONCLUSIONS: EELC alleviated the progression of HN by suppressing the activation of NF-κB, ASK1/JNK/c-Jun and JAK2/STAT3 signaling pathway, reducing the infiltration of inflammatory factors and uric acid accumulation in the kidney.

12.
Infect Drug Resist ; 13: 2509-2520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801789

RESUMO

Background: Candida albicans is associated with high mortality among immunocompromised patients. Resistance to and toxic side effects of antifungal drugs require the development of alternative antifungal agents. AMP-17 is a novel antimicrobial peptide derived from Musca domestica that exerts excellent antifungal effects against the Candida species. In this article, we discuss the potential mechanism of AMP-17 against C. albicans from the perspective of affecting the latter's cell external structure. Methods: Recombinant AMP-17 was prepared by prokaryotic expression system, and its anti-C. albicans activity was detected by microdilution method. Microscopy and scanning electron microscopy were used to examine morphological changes in C. albicans. Cell wall-specific staining method was used to detect the change of cell wall integrity of C. albicans after AMP-17 treatment. AMP-17-induced damage to the C. albicans cell membrane was analyzed by fluorescent probes and glycerol assay kit. The expression of genes related to fungal cell wall and cell-membrane synthesis was detected by qRT-PCR. Results: Morphological observations showed that the growth of C. albicans was significantly inhibited in AMP-17-treated cells; the cells appeared aggregated and dissolved, with severe irregularities in shape. Furthermore, AMP-17 damaged the integrity of C. albicans cell walls. The cell wall integrity rate of AMP-17-treated cells was only 21.7% compared to untreated cells. Moreover, the change of membrane dynamics and permeability suggested that the cell membrane was disrupted by AMP-17 treatment. Genetic analysis showed that after AMP-17 treatment, the cell wall synthesis-related gene FKS2 of C. albicans was up-regulated 3.46-fold, while the cell membrane ergosterol synthesis-related genes ERG1, ERG5, ERG6, and MET6 were down-regulated 5.88-, 17.54-, 13.33-, and 7.14-fold, respectively. Conclusion: AMP-17 treatment disrupted the cell wall integrity and membrane structure of C. albicans and is likely a novel therapeutic option for prevention and control of C. albicans infections.

13.
Am J Physiol Endocrinol Metab ; 319(3): E494-E508, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32691632

RESUMO

Hydroxysteroid 17ß dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males, 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity, specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.

14.
Medicine (Baltimore) ; 99(28): e19632, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664051

RESUMO

RATIONALE: Septic shock leads to multiple organ failure and increases mortality rate. We reported a critical patient with abdominal septic shock, which was the first case successfully treated with continuous renal replacement therapy (CRRT) and a newly designed endotoxin removal device oXiris in mainland China. PATIENT CONCERNS: A 51-year-old man developed gastric ulcer perforation after resection of a benign peritoneal tumor and had a second abdominal surgery. His blood pressure decreased to 70/40 mm Hg with oliguria, requiring large doses of noradrenaline and intravenous fluid for resuscitation. The abdominal cavity was not sutured after the second open surgery due to severe abdominal infection and distention. His leukocyte count was over 30109/L, while the blood lactic acid was 12.5 mmol/L and procalcitonin (PCT) was >100 ng/mL. DIAGNOSIS: Since the bacterial culture of peritoneal exudate showed positive with Enterobacter aerogenes and Pseudomonas aeruginosa after the second surgery, and the patient had severe low blood pressure, hyoxemia and oliguria, combined with the laboratory tests results, he was diagnosed with Gram-negative related septic shock, acute kidney injury, and multiple organ dysfunction. INTERVENTIONS: CRRT with oXiris membrane was performed for 80hours and followed by AN69 ST membranes during the subsequent 27 days. Antibiotics together with other medical treatment were applied to the patient in the meantime. OUTCOMES: At the end of 80 hours treatment with oXiris, PCT of the patient had decreased to 14.52 ng/mL and lactic acid decreased to 4.2 mmol/L. The total sequential organ failure assessment (SOFA) score decreased from 15 to 11. Urine output steadily increased to 250 mL/h, and vital signs and blood pressure were stable without noradrenaline. At the end of the 27 days of conventional CRRT, his kidney function had completely recovered with a total sequential organ failure assessment score (SOFA score) of 6. LESSONS: oXiris, with its enhanced endotoxin adsorption, appeared to accelerate improvement in organ dysfunction and ultimate survival in our patient. In critical patients with abdominal septic shock, oXiris is an important adjunctive consideration to supplement definitive source control and antimicrobial therapy.


Assuntos
Hemodiafiltração/instrumentação , Complicações Pós-Operatórias/terapia , Choque Séptico/terapia , Desintoxicação por Sorção/instrumentação , Anastomose Cirúrgica , Endotoxinas/isolamento & purificação , Gastrectomia , Humanos , Intestinos/cirurgia , Laparotomia , Masculino , Membranas Artificiais , Pessoa de Meia-Idade
16.
Huan Jing Ke Xue ; 41(5): 2398-2405, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608859

RESUMO

Tri-and hexavalent chromium have different chemical properties, and their levels of toxicity to plants are different. However, there is no limit set by the soil environmental quality risk control standard for Cr(Ⅲ) or Cr(Ⅵ). Therefore, studying the ecological toxicity of Cr has important implications for protecting the environment. Based on the dynamics of the Cr(Ⅲ) and Cr(Ⅵ) levels in soil solution collected from eight soils, the toxicity thresholds of the two Cr forms to barley roots were investigated through model calculation and correlation analysis under different soil properties. The results showed that both Cr forms and the soil properties had significant effects on the root length of barley. The effective concentrations of Cr(Ⅲ) added to the soils that led to 10% inhibition (EC10), 50% inhibition (EC50), and no-observed-effect concentrations (NOEC) were significantly higher than those of Cr(Ⅵ). The EC50 of Cr(Ⅲ) ranged from 298.8 to 2014.1 mg·kg-1 (6.7-fold variation); the EC50 of Cr(Ⅵ) ranged from 8.0 to 126.6 mg·kg-1 (15.8-fold variation). Under the same soil conditions, the EC50 of Cr(Ⅲ) was 2.8 to 101.7 times higher than that of Cr(Ⅵ), suggesting the higher phytotoxicity of Cr(Ⅵ) than Cr(Ⅲ). Correlation analysis showed that the pH and soil organic matter were the main factors that influenced the Cr toxicity thresholds, as indicated by the root length of barley. The concentration of chromium in the soil solution was below the detection limit of the TAS-990 when Cr(Ⅲ) was applied at 1280 mg·kg-1 (or less) to soils, whereas for Cr(Ⅵ), the level was 40 mg·kg-1 (or less). Cr(Ⅲ) adsorption to the soil was significantly stronger than that of Cr(Ⅵ). The toxicity of Cr(Ⅵ) was significantly higher than that of Cr(Ⅲ), which was also influenced by soil properties.


Assuntos
Poluentes do Solo/análise , Solo , Cromo , Hordeum , Raízes de Plantas/química
17.
Int Immunopharmacol ; 87: 106457, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32682254

RESUMO

BACKGROUNDS: Contrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. It has been demonstrated that microRNA-30c (miR-30c) was upregulated in the CIAKI. However, the underlying mechanism remain unclear. METHODS: The CIAKI was induced in miniature pig. The expression profile of miR-30c in the kidney was evaluated by qPCR. The pathways regulated by miR-30c was identified by qPCR and western blot on renal tubular epithelial cells isolated from miniature pig. Finally, the potential therapeutic application of targeting miR-30c was assessed in the pig model of CIAKI. RESULTS: The miR-30c was up-regulated in miniature pig with CIAKI. The miR-30c suppressed cell apoptosis, expression of NLRP3, the secretion of IL-1ß and caspase-1 p10 on renal cells stimulated by iohexol in vitro. In the pig model, miR-30c inhibited the CIAKI development. CONCLUSION: Our data demonstrated that the miR-30c induced by CIAKI could suppress cell apoptosis and kidney injury via targeting NLRP3. Therefore, targeting miR-30c might be a novel therapeutic candidate for CIAKI treatment and prevention.

18.
Am J Physiol Renal Physiol ; 319(4): F664-F673, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32715764

RESUMO

Tubular changes contribute to the development of renal pathologies in diabetic kidney disease (DKD), including interstitial fibrosis. It is unclear how tubular cells relay signals to interstitial fibroblasts. Recently, exosomes have been recognized as crucial mediators of intercellular communication. We hypothesized that exosomes secreted from tubular cells may stimulate fibroblasts for interstitial fibrosis in DKD. In this study, we isolated and purified exosomes from the renal cortex of DKD mice and high glucose-treated mouse proximal tubular cells. Compared with nondiabetic mice, exosome secretion in kidney tissues decreased in DKD mice. Likewise, high glucose incubation reduced exosome secretion in mouse kidney proximal tubular BUMPT cells. To study the effect of tubular cell exosomes on fibroblasts, exosomes from BUMPT cells were added to renal fibroblast NRK-49F cell cultures. Notably, exosomes from high glucose conditioned BUMPT cells induced higher proliferation, significant morphological change, and substantial production of fibronectin, α-smooth muscle actin, and collagen type Ι in NRK-49F fibroblasts. Proteomics analysis was further performed to profile the proteins within tubular cell exosomes. Interestingly, 22 proteins were found to be differentially expressed between tubular exosomes derived from high glucose conditioned cells and those from normal glucose conditioned cells. Cytoscape analysis suggested the existence of two protein-protein interaction networks in these exosomal differentially expressed proteins. While one of the protein-protein interaction networks comprised enolase 1 (Eno1), heat shock protein family A member 8 (Hspa8), thioredoxin 1 (Txn1), peptidylprolyl isomerase A (Ppia), phosphoglycerate kinase 1 (Pgk1), DNA topoisomerase II-ß (Top2b), and ß-actin (Actb), the other had the family proteins of human leucocyte antigen F (Ywhag), a component of the ND10 nuclear body (Ywhae), interferon regulatory factor-8 (Ywhaq), and human leucocyte antigen A (Ywhaz). Gene expression analysis via Nephroseq showed a correlation of Eno1 expression with DKD clinical manifestation. In conclusion, DKD is associated with a decrease in exosome secretion in renal tubular cells. Exosomes from high glucose conditioned tubular cells may regulate the proliferation and activation of fibroblasts, contributing to the paracrine signaling mechanism responsible for the pathological onset of renal interstitial fibrosis in DKD.

19.
Ren Fail ; 42(1): 629-637, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32660366

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a clinical and pathological syndrome with heterogenous manifestation and progression. Complement activation is involved in the disease. However, the clinical significance of C4 deposition in IgAN is obscure. METHODS: A multicenter retrospective study was conducted in biopsy-proven IgAN patients. Based on mesangial C4 deposition, patients were divided into two groups. The baseline clinical data and immunopathological phenotypes were compared. The composite endpoint was defined as eGFR decline greater than 50%, doubling of baseline serum creatinine, the occurrence of end-stage renal disease (ESRD). RESULTS: A total of 642 IgAN patients were recruited, with 41 patients showing mesangial C4 deposition. The mesangial C4 positive group showed lower serum albumin, higher proteinuria, and a higher rate of IgG, IgM, and C1q mesangial deposition. After a median follow-up of 43.18 months, 81 (12.62%) patients achieved the composite endpoint. The multivariate Cox regression models identified glomerular C4 deposition (hazard ratios [HR] = 3.22, 95% confidence intervals [CI] = 1.51-6.87, p < 0.01), global sclerosis (G1 vs. G0, HR = 1.90, 95%CI = 1.02-3.52, p = 0.04; G2 vs. G0, HR = 3.72, 95%CI = 1.98-7.00, p < 0.01), male (HR = 1.80, 95%CI = 1.10-2.97, p = 0.02), serum creatinine (HR = 1.01, 95%CI = 1.00-1.01, p < 0.01), triglyceride (HR = 1.17, 95%CI = 1.01-1.35, p = 0.04), proteinuria (HR = 1.07, 95%CI = 1.01-1.13, p = 0.02), serum C3 level (HR = 0.05, 95%CI = 0.01-0.25, p < 0.01), and serum C4 level (HR = 99.59, 95%CI = 8.69-1140.89, p < 0.01) as independent risk factors for poor renal outcomes. CONCLUSIONS: Glomerular mesangial C4 deposition and global sclerosis are independent predictors for poor prognosis in IgAN patients.

20.
Huan Jing Ke Xue ; 41(2): 962-969, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608758

RESUMO

Cadmium (Cd) is a highly toxic heavy metal. Brassica rapa (pak choi) is a vastly common vegetable, which readily accumulates Cd. Given the current conditions of Cd contamination in domestic soil, it is important to reduce Cd accumulation in the edible part of pak choi. Research has shown that selenium (Se) can regulate Cd uptake by plants. Cd accumulation (three cultivars) and Cd uptake kinetics in pak choi were investigated under hydroponic conditions. Results showed that the three levels of selenite significantly reduced Cd content in the Hangzhouyoudonger shoot by 50%, while the levels in Suzhouqinggen and Shanghaiqing shoots were not significantly decreased with elevated levels of selenite. Selenite reduces the Cd translocation factors, and higher levels had more obvious effects; 50 µmol·L-1 of selenite significantly decreased the factors by 50% in Hangzhouyoudonger and Suzhouqinggen shoots. Selenite also increased iron (Fe) and manganese (Mn) contents in pak choi, especially in the Hangzhouyoudonger shoot, where 50 µmol·L-1 increased the Fe content by approximately 50%. In the uptake kinetics of Cd, both selenite and selenate significantly increased Cd uptake rates and Vmax by over 100%. Therefore, Se could reduce Cd accumulation in pak choi. This also depended on the tested cultivar. Therefore, reduction effects of Se on the Cd content mainly stemmed from the alteration of Cd translocation in pak choi instead of the uptake competition between Cd and Se.


Assuntos
Brassica rapa/metabolismo , Cádmio/metabolismo , Brotos de Planta/metabolismo , Selênio/metabolismo , Poluentes do Solo/metabolismo , Ácido Selênico , Ácido Selenioso
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