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1.
J Am Soc Nephrol ; 34(1): 73-87, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36719147

RESUMO

BACKGROUND: Hypoxia and hypoxia-inducible factors (HIFs) play essential and multiple roles in renal ischemia-reperfusion injury (IRI). Dendritic cells (DCs) comprise a major subpopulation of the immunocytes in the kidney and are key initiators and effectors of the innate immune responses after IRI. The role of HIF-2α in DCs remains unclear in the context of renal IRI. METHODS: To investigate the importance of HIF-2α in DCs upon renal IRI, we examined the effects of DC-specific HIF-2α ablation in a murine model. Bone marrow-derived DCs (BMDCs) from DC-specific HIF-2α-ablated mice and wild-type mice were used for functional studies and transcriptional profiling. RESULTS: DC-specific ablation of HIF-2α led to hyperactivation of natural killer T (NKT) cells, ultimately exacerbating murine renal IRI. HIF-2α deficiency in DCs triggered IFN-γ and IL-4 production in NKT cells, along with upregulation of type I IFN and chemokine responses that were critical for NKT cell activation. Mechanistically, loss of HIF-2α in DCs promoted their expression of CD36, a scavenger receptor for lipid uptake, increasing cellular lipid accumulation. Furthermore, HIF-2α bound directly to a reverse hypoxia-responsive element (rHRE) in the CD36 promoter. Importantly, CD36 blockade by sulfo-N-succinimidyl oleate (SSO) reduced NKT cell activation and abolished the exacerbation of renal IRI elicited by HIF-2α knockout. CONCLUSIONS: Our study reveals a previously unrecognized role of the HIF-2α/CD36 regulatory axis in rewiring DC lipid metabolism under IRI-associated hypoxia. These findings suggest a potential therapeutic target to resolve long-standing obstacles in treatment of this severe complication.


Assuntos
Rim , Traumatismo por Reperfusão , Animais , Camundongos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Lipídeos/farmacologia , Traumatismo por Reperfusão/metabolismo
2.
Am J Transplant ; 23(8): 1264-1267, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36695695

RESUMO

En bloc kidney transplantation (EBKT) to adults from preterm neonates following donation after circulatory death has not been described in the literature. We report 2 successful cases of EBKT from preterm neonatal donation after circulatory death donors weighing <1.2 kg to adult recipients. The first case was a preterm female infant born at 29 weeks' gestational age, weighing 1.07 kg. The recipient was a 34-year-old woman weighing 75 kg. At the 9-month follow-up, the patient demonstrated excellent graft function with a creatinine concentration of 1.48 mg/dL. The second donor was a preterm female infant born at 29 weeks and 5 days' gestation, weighing 1.17 kg. The recipient was a 25-year-old woman weighing 46 kg. By 5 months post surgery, the serum creatinine level had gradually decreased to 1.47 mg/dL. In our experience, EBKT from preterm neonates <30 weeks' gestation and weighing <1.2 kg has demonstrated acceptable short- to medium-term results.


Assuntos
Transplante de Rim , Lactente , Recém-Nascido , Adulto , Humanos , Feminino , Sobrevivência de Enxerto , Estudos Retrospectivos , Doadores de Tecidos , Creatinina
3.
Mikrochim Acta ; 190(8): 284, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37417992

RESUMO

A spiral interdigitated MXene-assisted field effect transistor (SiMFETs) was proposed for determination of IL-6 in patients with kidney transplantation infection. Our SiMFETs demonstrated enhanced IL-6 detection range of 10 fg/mL-100 ng/mL due to the combination of optimized transistor's structure and semiconducting nanocomposites. Specifically, on one hand, MXene-based field effect transistor drastically amplified the amperometric signal for determination of IL-6; on the other hand, the multiple spiral structure of interdigitated drain-source architecture improved the transconductance of FET biosensor. The developed SiMFETs biosensor demonstrated satisfactory stability for 2 months, and favorable reproducibility and selectivity against other biochemical interferences. The SiMFETs biosensor exhibited acceptable correlation coefficient (R2=0.955) in quantification of clinical biosamples. The sensor successfully distinguished the infected patients from the health control with enhanced AUC of 0.939 (sensitivity of 91.7%, specificity of 86.7%). Those merits introduced here may pave an alternative strategy for transistor-based biosensor in point-of-care clinic applications.


Assuntos
Técnicas Biossensoriais , Transplante de Rim , Humanos , Interleucina-6 , Reprodutibilidade dos Testes
4.
Int Wound J ; 20(1): 140-144, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35644604

RESUMO

To analyse risk factors for impaired wound healing after kidney transplantation to guide clinical decision-making. A retrospective analysis was performed on patients who received kidney transplantation from January 1, 2019, to May 1, 2021, at Kidney Transplantation Center in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. A case-control study was used to identify a cohort of patients with similar baseline characteristics according to 1:4 ratio. Patients were divided into two groups according to whether there was impaired wound healing after surgery. The basic data and clinical examinations between the two groups were compared, and the risk factors for impaired wound healing after kidney transplantation were analysed using univariate and multivariate analyses. According to the data type, independent samples t-test or Chi-squared test was used for comparison between groups. Furthermore, multivariate logistic regression analysis was used to analyse different risk factors and calculate the odds ratio (OR) and 95% confidence interval (CI) of each factor. A total of 18 patients showed impaired wound healing after kidney transplantation. And we conducted 72 statically matched controls. Age, diabetes, transplant types, body mass index (BMI), albumin, haemoglobin, and wound infection were statistically different between the two groups. The factors with statistically significant differences in univariate analysis were included in multivariate logistic regression analysis. The results showed that BMI > 25, fasting blood glucose level, albumin level, and prealbumin level were independent risk factors for impaired wound healing after kidney transplantation. Risk factors for impaired wound healing after kidney transplantation can be detected after surgery. Strengthening postoperative monitoring and early intervention of recipients with such factors may effectively prevent impaired wound healing after kidney transplantation.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Estudos Retrospectivos , Estudos de Casos e Controles , Complicações Pós-Operatórias/etiologia , China/epidemiologia , Fatores de Risco , Cicatrização
5.
Int J Mol Sci ; 23(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35897631

RESUMO

Great efforts have been made to separate micro/nanoparticles in small-volume specimens, but it is a challenge to achieve the simple, maneuverable and low-cost separation of sub-microliter suspension with large separation distances. By simply adding trace amounts of cations (Mg2+/Ca2+/Na+), we experimentally achieved the size-dependent spontaneous separation of colloidal particles in an evaporating droplet with a volume down to 0.2 µL. The separation distance was at a millimeter level, benefiting the subsequent processing of the specimen. Within only three separating cycles, the mass ratio between particles with diameters of 1.0 µm and 0.1 µm can be effectively increased to 13 times of its initial value. A theoretical analysis indicates that this spontaneous separation is attributed to the size-dependent adsorption between the colloidal particles and the aromatic substrate due to the strong hydrated cation-π interactions.


Assuntos
Nanopartículas , Sódio , Adsorção , Cátions , Suspensões
6.
Pharmacol Res ; 170: 105712, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091010

RESUMO

Renal ischemia/reperfusion injury (IRI) is the major cause of acute kidney injury. However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we performed RNA sequencing to systematically compare the transcriptome differences between IR injured kidneys and sham kidneys. We observed that mitochondrial dynamics was destructed in renal IRI. Expression of mitochondrial fusion-associated genes was reduced, whereas expression of mitochondrial fission-related genes was increased in renal IRI, and these findings were further confirmed by mitochondrial morphological observations. By screening 19 purinergic receptors, we noticed that P2RX1 expression was markedly upregulated in renal IRI. RNA sequencing and mitochondrial morphological observations revealed that mitochondrial dynamics was preserved in P2RX1 genetic knockout (P2rx1-/-) mice. Neutrophil extracellular traps (NETs) were reported to be essential for tissue injury in renal IRI, but the detailed mechanism remained unclear. In the present study, we found that P2RX1 favored the formation of neutrophil extracellular traps (NETs) in IRI, and NETs was essential for the impairment of mitochondrial dynamics. Mechanistically, P2RX1-involved metabolic interaction between platelets and neutrophils supported NETs formation. Activation of P2RX1 promoted platelets ATP release, which subsequently contributed to neutrophil glycolytic metabolism and NETs generation.


Assuntos
Injúria Renal Aguda/prevenção & controle , Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X1/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Trifosfato de Adenosina/metabolismo , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Modelos Animais de Doenças , Armadilhas Extracelulares/metabolismo , Regulação da Expressão Gênica , Glicólise/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Receptores Purinérgicos P2X1/genética , Receptores Purinérgicos P2X1/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais
7.
Nephrology (Carlton) ; 26(8): 684-691, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33866646

RESUMO

AIM: Urine cell-free DNA (cfDNA) is a new type of liquid biopsy biomarker used in tumours and allograft injury detection but is highly susceptible to degradation by the high nuclease activity of urine. This study presents a newly developed urine cfDNA preservation solution (AlloU), efficient for examining allograft injury in kidney transplant recipients (KTx). METHODS: We established urine-preserve solution called AlloU based on the response-surface methodology, with two commercial collection reagents (Streck and K2 EDTA preservation solution) included for analysis. A total of 120 urine samples from KTx patients, including morning, nocturnal and random urine from specific storage time were subjected to investigation. The urine total cfDNA concentration was quantified by fluorometry, fragment distribution was analysed by qPCR, and donor-derived cfDNA (ddcfDNA) was detected by next-generation sequencing. RESULTS: Urine total cfDNA concentration and fragment size of samples preserved with AlloU and Streck did not change significantly within 5 days whereas the ddcfDNA also did not change significantly within 7 days. However, compared with EDTA, the total cfDNA concentration increased significantly on the third day. When compare with different urine types, it was found that samples preserved with AlloU showed no significant differences in total cfDNA concentration, fragment size, and ddcfDNA concentration, however, the SD for morning urine was significantly smaller in total cfDNA and ddcfDNA concentration. CONCLUSION: To the best of our knowledge, this is the first report to verify the dynamics of urine cfDNA in KTx, especially in the analysis impact of different urine types on cfDNA detection.


Assuntos
Ácidos Nucleicos Livres/urina , Transplante de Rim , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos , Estudos Prospectivos
8.
Water Res X ; 24: 100238, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39155948

RESUMO

Water disinfection by copper vessels has been prevalent over thousands of years. Unfortunately, people are still suffering from the bacterial pollution in drinking water. Here we show that, only through steeping with tiny amounts of common plant leaves, the room-temperature water in copper pots has unexpectedly high antibacterial ability. Remarkably, copper ions released from copper pots into water are in concentrations lower than the WHO safety threshold for drinking water, and have effective antibacterial ability when water contains specific leave components (polyphenols and/or lignin). Our computations show that the key to enhance antibacterial ability is the great increase in the proportion of Cu+ induced by aromatic rings in these leave components, which has been demonstrated by our experiments. The findings may disclose the mystery of copper vessels for water disinfection, and more importantly, provide effective antibacterial applications in industries and daily lives, by safely using copper ions together with biocompatible natural substances.

9.
Adv Healthc Mater ; : e2401347, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819639

RESUMO

Identifying infected stones is crucial due to their rapid growth and high recurrence rate. Here, the calcium-magnesium dual-responsive aggregation-induced emission (AIE)-active probe TCM-5COOH (Tricyano-methlene-pyridine-5COOH), distinctively engineered to distinguish high-threat infection calculi from metabolic stones, is presented. Upon incorporation of flexible alkyl carboxyl group, TCM-5COOH featuring five carboxyl moieties demonstrates excellent water solubility and enhanced penetration into porous infectious stones. The robust chelation of TCM-5COOH with stone surface-abundant Ca2+ and Mg2+ inhibits vibrational relaxation, thus triggering intense AIE signals. Remarkably, the resulting complex exhibits high insolubility, effectively anchoring within the porous structure of the infection calculi and offering prolonged illumination. Jobs' plot method reveals similar response characteristics for Ca2+ and Mg2+, with a 1:2 coordination number for both ions. Isothermal titration calorimetry (ITC) results demonstrate higher enthalpy change (ΔH) and lower entropy change (ΔS) for the reaction, indicating enhanced selectivity compared to TCM-4COOH lacking the alkyl carboxyl group. Synchrotron X-ray absorption fine spectroscopy (XAFS) validates TCM-5COOH's interaction with Ca2+ and Mg2+ at the microlevel. This dual-responsive probe excels in identifying infectious and metabolic calculi, compatible with endoscopic modalities and laser excitation, thereby prompting clinical visualization and diagnostic assessment.

10.
Heliyon ; 9(9): e19970, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37810140

RESUMO

Desiccation patterns of plasma sessile drops have attracted increasing attention, not only because of the fantastic underlying physics, but also due to their potential of being health diagnostic tools. However, plasma is a multicomponent system, which contains macromolecular proteins and inorganic salts; these components have complicated interactions to define pattern morphologies. Unfortunately, mechanisms of coupling effects of main components on pattern morphologies are still not clear, thus limiting their diagnostic applications. Here we show the coupling effects of human serum albumin (HSA) and sodium chloride (NaCl) on plasma desiccation patterns. Our experiments indicate that NaCl enhances the "coffee ring" effect of HSA to promote its aggregation at the peripheral region and narrows down its aggregation area; this would influence the distribution of internal stresses, resulting in a larger number of radial cracks, with a larger width but a shorter length, than cracks in pure HSA. In the meantime, HSA experiences the gelation process that propagates from the peripheral region to central region and causes the spatiotemporal deviation in the degree of solidification, which induces a higher concentration of NaCl in the central region, thus leading to the formation of crystal patterns. Our further experiments demonstrate that these characteristic patterns are correlated to the variation in the concentration of NaCl, which can be caused by hyponatremia and hypernatremia in real biofluids. Our findings not only provide a new mechanistic insight into biological desiccation patterns, but also bridge the gap between the understanding and diagnostic applications of these desiccation patterns.

11.
JAMA Netw Open ; 6(12): e2349538, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150251

RESUMO

Importance: Studies exploring the association of body weight and metabolic status with graft function deterioration (GFD) after kidney transplantation have produced inconsistent findings. Few studies have examined whether metabolically healthy overweight or obesity (MHO) may contribute to GFD. Objective: To evaluate associations of overweight or obesity and metabolic disorders with GFD in recipients of kidney transplant. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted from January 1, 2020, through June 30, 2021, with a follow-up period of 2 years after kidney transplantation. Participants included adult recipients of cadaveric kidney transplant in 4 transplantation centers in China. Participants were classified as 4 metabolic phenotypes according to their BMI and metabolic status. Data were analyzed from July to August 2023. Exposures: Overweight and obesity were characterized by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 24 or greater. Metabolic disorder was identified by existence of a minimum of 2 of 4 conditions: hypertension, hyperglycemia, increased triglyceride, and decreased high-density lipoprotein cholesterol. Main Outcome and Measures: The main outcome was GFD, defined as a decrease in estimated glomerular filtration rate of at least 25% within 6 months to 2 years after transplant. Results: A total of 1260 adult recipients of cadaveric kidney transplant (mean [SD] age, 43.97 [11.51] years; 755 [59.92%] male) were included in the study, and 127 (10.08%) participants experienced the primary outcome of GFD during follow-up. After accounting for confounding factors in multivariable analyses, overweight or obesity (odds ratio [OR], 1.64; 95% CI, 1.10-2.44; P = .02) and metabolic disorder (OR, 1.71; 95% CI, 1.12-2.63; P = .01) were associated with increased risk of GFD. The MHO subgroup exhibited a greater risk for GFD (OR, 2.37; 95% CI, 1.01-5.57; P = .048) compared with participants who did not have overweight or obesity or metabolic disorder. All components of metabolic disorder, with the exception of elevated triglyceride, were associated with GFD. There was a dose-response association of number of metabolic disorder components (OR per 1 additional condition, 1.40; 95% CI, 1.20-1.63; P < .001) and BMI (OR per 1-unit increase, 1.90; 95% CI, 1.03-1.15; P = .002) with increased risk for GFD. A nonlinear association was observed between BMI and risk of GFD. Conclusions and Relevance: In this cohort study of recipients of cadaveric kidney transplant, individuals with overweight or obesity or metabolic disorder had a significantly higher risk of experiencing GFD. Individuals with MHO had an elevated risk for graft function deterioration. Additional studies with larger sample size and longer follow-up are necessary to validate our findings.


Assuntos
Transplante de Rim , Obesidade Metabolicamente Benigna , Adulto , Feminino , Humanos , Masculino , Cadáver , Transplante de Rim/efeitos adversos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Estudos Retrospectivos , Triglicerídeos , Pessoa de Meia-Idade
12.
Front Immunol ; 14: 1117297, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056767

RESUMO

Background: Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes. Method: The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections. Results: The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable. Conclusion: We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.


Assuntos
Transplante de Rim , Traumatismo por Reperfusão , Camundongos , Humanos , Animais , Mitofagia/genética , Rim/metabolismo , Transplante de Rim/efeitos adversos , Neutrófilos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo
13.
J Nephrol ; 35(7): 1895-1899, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35852773

RESUMO

De novo systemic atypical hemolytic uremic syndrome (aHUS) post-kidney transplant is an uncommon entity associated with unfavorable outcome. We herein report a case of systemic and fulminant de novo aHUS accompanied by heart and respiratory failure in a 48-year-old male receiving ABO-incompatible living-related kidney transplant who was successfully treated with the anti-C5 monoclonal antibody eculizumab with complete recovery of allograft function. Genetic testing demonstrated a novel pathogenic heterozygous complement factor H-related 1 gene mutation in both the donor and the recipient. Our study highlights the high risks of post-transplant aHUS due to the complement gene mutations in both donor and recipient in living-related transplantation. Early intervention with eculizumab may be effective for reversing systemic aHUS in kidney transplant recipients.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Transplante de Rim , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Proteínas Inativadoras do Complemento C3b/genética , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação
14.
Front Public Health ; 10: 944137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117592

RESUMO

Objective: To investigate the risk factors of infectious diseases in adult kidney transplantation recipients and to establish a simple and novel nomogram to guide the prophylactic antimicrobial therapy. Methods: Patients who received kidney transplantation between January 2018 and October 2021 were included in the study and were divided into a training and a testing set at a 1:1 ratio. Risk factors correlated to infectious diseases were selected using a Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The prediction model was built by incorporating the variables selected by the LASSO model into a logistic regression equation. Calibration curves and receiver operating characteristic (ROC) curves were also applied to assess the model calibration and discrimination. A nomogram consisting of the selected factors was established to provide individualized risks of developing infections. Decision curve analysis (DCA) was adopted to estimate the net benefit and reduction in interventions for a range of clinically reasonable risk thresholds. Results: In all, 863 adult kidney recipients were included in the study, and 407 (47.16%) of them developed infectious diseases during the 3-year follow-up period. A total of 8 variables were selected using LASSO regression and were retained for subsequent model construction and infection prediction. The area under the curve (AUC) was 0.83 and 0.81 in the training and testing sets, with high F scores of 0.76 and 0.77, sensitivity of 0.76 and 0.81, and specificity of 0.88 and 0.74, respectively. A novel nomogram was developed based on 8 selected predictors (requirement for albumin infusion, requirement for red blood cell infusion, triglyceride, uric acid, creatinine, globulin, neutrophil percentage, and white blood cells). The net benefit indicated that the nomogram would reduce unnecessary interventions at a wide range of threshold probabilities in both sets. Conclusions: Adult kidney transplantation recipients are high-risk hosts for infectious diseases. The novel nomogram consisting of 8 factors reveals good predictive performance and may promote the reasonable antimicrobial prescription. More external validations are required to confirm its effectiveness for further clinical application.


Assuntos
Doenças Transmissíveis , Transplante de Rim , Adulto , Albuminas , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Creatinina , Humanos , Nomogramas , Triglicerídeos , Ácido Úrico
15.
Stem Cells Int ; 2022: 1981798, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35859725

RESUMO

Exosomes derived from mesenchymal stem cell (MSC) alleviate kidney damage through autophagy. This study determined whether MSCs relieve renal fibrosis and inhibit autophagy by exosome transfer of miRNA-122a. The gene expression involved in the mTOR signaling pathway and autophagy was assessed in TGF-ß1-treated human renal tubular epithelial cells (HK-2) and unilateral ureteral obstruction (UUO) mice before and after MSC-derived exosomes and miRNA-122a mimic treatment. Small RNA (sRNA) next-generation sequencing was also performed on TGF-ß1-treated HK-2 cells. MSC-derived exosomes relieve fibrosis caused by TGFß in HK-2 via regulation of the mTOR signaling pathway and downstream autophagy. Furthermore, we found that MSC-derived exosomes mediate miRNA-122a to relieve renal fibrosis in HK-2 cells in response to TGF-ß1 through the regulation of mTOR signaling and autophagy. In the UUO mouse model, miRNA-122a mimic-transfected MSC treatment and its combination with 3-MA both recapitulated the same results as the in vitro experiments, along with reduced expansion of renal tubule, interstitial expansion, and preservation of kidney architecture. The antifibrotic activity of MSC-derived exosomes after renal fibrosis occurs partially by autophagy suppression via excreted exosomes containing mainly miRNA-122a. These findings indicate that the export of miRNA-122a via MSC-derived exosomes represents a novel strategy to alleviate renal fibrosis.

16.
Int J Infect Dis ; 125: 209-215, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36243280

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation. METHODS: Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function. RESULTS: Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001). CONCLUSION: Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.


Assuntos
Transplante de Rim , Pneumocystis carinii , Pneumonia por Pneumocystis , Adulto , Humanos , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol , Transplante de Rim/efeitos adversos , Estudos Retrospectivos
17.
Transpl Immunol ; 74: 101667, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35835294

RESUMO

BACKGROUND: There is a lack of epidemiological studies on the course and clinical characteristics of Parvovirus B19 (B19V) infections in kidney transplant (KT) recipients. This study was undertaken to provide recommendations for clinical B19V infection diagnosis and treatment. METHODS: Serum samples of KT recipients were regularly collected and tested for B19V-DNA copies, B19V-IgG/IgM levels, as well as hematological parameters and functions of kidney and liver. The course of B19V infection was described according to the results of serology and DNA testing, and the clinical and epidemiological data were combined for analysis. RESULTS: 75% B19V infections occurred within 2 weeks after KT(n = 9). The infection rate of B19V in KT recipients was high, namely 10.17% (n = 12). The number of 10 patients IgM antibodies against B19V (IgM+) and theDNA B19V (DNA+), whereas 2 patients were IgM negative (IgM-) but DNA+. The B19V infected KT patients showed several symptoms, including anemia (100%), reduction of platelets (8.33%), and damage to liver (75%) and kidney function (16.67%) Patients with progressive anemia in the first two weeks after KT, which combined with the decrease of reticulocytes, are more likely to have B19V infection. Associations of four main therapeutic risk factors for B19V infections in KT patients have been analyzed. B19V infection was associated with use of basiliximab (OR = 1.19; 95%- CI: 1.08-1.32; P = 0.003) and use of thymoglobulins (OR = 0.84; 95%-CI: 0.76-0.93; P = 0.003). CONCLUSIONS: Doctors should be alert to B19V infection, especially in the immunodeficient patients within the first two weeks after transplantation.


Assuntos
Anemia , Eritema Infeccioso , Transplante de Rim , Infecções por Parvoviridae , Parvovirus B19 Humano , Anticorpos Antivirais , China/epidemiologia , DNA Viral , Eritema Infeccioso/complicações , Eritema Infeccioso/diagnóstico , Eritema Infeccioso/epidemiologia , Hospitais de Ensino , Humanos , Imunoglobulina M , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/epidemiologia , Parvovirus B19 Humano/genética , Estudos Prospectivos
18.
Ann Transplant ; 26: e933313, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34489392

RESUMO

BACKGROUND The aim of this study was to evaluate the efficacy and safety of Sofosbuvir/Velpatasvir prophylaxis in hepatitis C virus (HCV)-negative recipients who received a transplant kidney from HCV-infected donors. MATERIAL AND METHODS This retrospective cohort study enrolled consecutive HCV-negative recipients between January 2019 and February 2021. All the recipients were treated with Sofosbuvir/Velpatasvir (400 mg/100 mg) once daily for 12 weeks after receiving a transplant kidney from HCV-infected donors. We collected data on renal function and liver function and HCV RNA were collected during the study. We also compared the rates of adverse events. RESULTS A total of 26 patients were included in the cohort. All the recipients (100%) completed 12 weeks of treatment and the entire follow-up. All recipients (100%) had negative HCV RNA, but 4 recipients (15.4%) were HCV antibody (Ab)-positive after transplantation. Fifteen adverse events (57.7%) occurred during the study. Three recipients (11.5%) experienced graft rejection, 6 recipients (23.1%) had delayed graft function, and 3 recipients (11.5%) had bleeding. However, none of them were related to study medication. Renal function was stable in all patients. CONCLUSIONS Sofosbuvir/Velpatasvir pre- and post-transplantation treatment was effective and safe in HCV-uninfected recipients who received a transplant kidney from HCV-infected donors.


Assuntos
Carbamatos , Hepatite C , Compostos Heterocíclicos de 4 ou mais Anéis , Transplante de Rim , Sofosbuvir , Adulto , Idoso , Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Adulto Jovem
19.
J Colloid Interface Sci ; 562: 333-341, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-31855796

RESUMO

Cellulose nanofibers (CNF) are promising nanomaterials for functional inks and printed sensors, although the potential applications are currently limited by the available functionalization methods. This work outlines a convenient method to grow a novel and highly conductive network of single-crystalline gold nanowires (AuNW) on CNF for use in conductive inks and printed sensors. The CNF are able to reduce Au (III) precursors to Au (0) monomers and generate nucleation sites for the subsequent monomer-by-monomer growth of Au nanocrystals; sodium citrate is used to control the reduction kinetics and the crystal growth. The growth of these AuNW/CNF materials is a three-step process of redox reaction, isotropic nucleation and anisotropic crystallization: the morphology and crystal structure of Au nanocrystals on CNF can be controlled by adjusting the reaction temperature and concentrations of citrate and CNF. The AuNW/CNF materials obtained have been formulated into highly conductive and atmospherically stable inks for use in either directly writing or screen printing. We have demonstrated AuNW/CNF-printed sensors with highly controllable electrical conductivity as well as excellent stability against rinsing and immersion by water and ethanol.

20.
ACS Sens ; 4(6): 1701-1709, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31099244

RESUMO

The renewed interest in plasma desiccation patterns focuses on the potential of these patterns to be developed into a platform of low-cost and facile diagnostic methods to interpret health conditions of donors. During desiccation, several physical mechanisms are simultaneously acting on the plasma sessile drop; these include material redistribution, buildup/release of local internal stresses, protein aggregation, and salt crystallization. After desiccation, cracking patterns and "superimposed" crystal-like patterns are formed. It has been reported that these characteristic patterns were influenced by changes in plasma compositions caused by diseases. Potential applications of these patterns in diagnosis are, however, limited by our understanding of formation mechanisms of cracking patterns and chemical compositions of crystal-like patterns. To address these limitations, this research studied morphologies of desiccated plasma patterns and the influence of sodium chloride to the pattern formation at both macroscopic and microscopic levels. Experimental results show that cracking patterns of plasma from healthy adults form throughout the desiccated deposit; propagation directions of cracks are found to have correlations to local dominant stresses, which are governed by the development of gelation. Crystal-like patterns are located in the drop center, which are caused by the heterogeneous distribution of macromolecular proteins and sodium chloride within the plasma sessile drop during desiccation; these patterns are influenced by the concentration of sodium chloride. With the increase of the concentration of sodium chloride, the distribution area of crystal-like patterns enlarges; whereas, the number of cracks decreases.


Assuntos
Sangue , Dessecação , Cristalização , Teste em Amostras de Sangue Seco , Humanos , Cloreto de Sódio/química , Propriedades de Superfície
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