Highly Selective Purification of Plasma Extracellular Vesicles Using Titanium Dioxide Microparticles for Depicting the Metabolic Signatures of Diabetic Retinopathy.

Extracellular vesicle (EV) cargos with regular fluctuations hold the potential for providing chemical predictors toward clinical diagnosis and prognosis. A plasma sample is one of the most important sources of circulating EVs, yet the technical barrier and cost consumption in plasma-EV isolation still limit its application in disease diagnosis and biomarker discovery. Here, we introduced an easy-to-use strategy that allows selectively purifying small EVs (sEVs) from human plasma and detecting their metabolic alternations. Fe3O4@TiO2 microbeads with a rough island-shaped surface have proven the capability of performing efficient and reversible sEV capture owing to the phospholipid affinity, enhanced binding sites, and size-exclusion-like effect of the rough TiO2 shell. The proposed system can also shorten the separation procedure from hours to 20 min when compared with the ultracentrifugation method and yield approximately 108 sEV particles from 100 µL of plasma. Metabolome variations of sEVs among progressive diabetic retinopathy subjects were finally studied, observing a cluster of metabolites with elevated levels and suggesting potential roles of these sEV chemicals in diabetic retinopathy onset and progression. Such a scalable and flexible EV capture system can be seen as an effective analytical tool for facilitating plasma-based liquid biopsies.

Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease.

OBJECTIVE: Early diagnosis of diabetic kidney disease (DKD) has long been a complex problem. This study aimed to analyze the metabolomic characteristics of plasma extracellular vesicles (EVs) at different stages of DKD in order to evaluate the metabolites of plasma EVs and select new biomarkers for the early diagnosis of DKD. PATIENTS AND METHODS: A total of 78 plasma samples were collected, including samples from 20 healthy controls, 20 patients with type 2 diabetes mellitus (T2DM), 18 patients with DKD stage III, and 20 patients with DKD stage IV. In addition, EVs were isolated for metabolomics analysis. RESULTS: The results identified differences in EV metabolomic characteristics in DKD patients at different stages, as well as significant differences in EV metabolomics between T2DM patients without DKD and patients with DKD. Ten Significantly differential metabolites were associated with the occurrence and progression of DKD. Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid were identified as potential early biomarkers for DKD, showing excellent predictive performance. CONCLUSION: Uracil, LPC(O-18:1/0:0), sphingosine 1-phosphate, and 4-acetamidobutyric acid exhibited potential as suitable biomarkers for early DKD diagnosis. Unexpectedly, combining these four candidate metabolites resulted in enhanced predictive ability for DKD.

A spontaneous pregnancy and successful delivery in a Chinese female with Silver-Russell syndrome accompanied by gestational diabetes mellitus.

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by severe intrauterine and postnatal growth retardation and typical dysmorphic features including body asymmetry, relative macrocephaly, protruding forehead, and feeding difficulties. Previous descriptions of SRS focus on the management of specific issues in children. Herein, we present clinical and metabolic characteristics of an adult woman with SRS accompanied by gestational diabetes mellitus (GDM). Given the rare circumstances presented in our case, the emerging questions concerning the management of metabolic issues and fertility potential in adult SRS patient deserve more attention. Further, long-term follow up is essential to gain future insights into the natural history and optimal management in adulthood.

[Analysis of AVPR2 gene mutation in a pedigree affected with congenital nephrogenic diabetes insipidus].

OBJECTIVE: To detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced. RESULTS: The patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation. CONCLUSION: The congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Tumor-induced osteomalacia with the culprit lesion located in the palm: a case report.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. We herein report a rare case of TIO in a 58-year-old Chinese man who presented with a large lump in the right palm. Clinical, biochemical, and radiological assessments were performed. Laboratory examination showed severe hypophosphatemia, phosphaturia, an elevated serum alkaline phosphatase level, and an elevated serum fibroblast growth factor 23 (FGF-23) level. Dual-energy X-ray absorptiometry showed low bone mineral density. Magnetic resonance imaging revealed an irregular mass located in the right palm and abnormal findings in several metacarpal bones. During the operation, the surgeons found that the tumor had penetrated the surrounding muscles. The tumor had unique characteristics of local tissue invasion. The patient's symptoms fully resolved and his serum phosphorus level normalized, although his serum FGF-23 level remained slightly high in the postoperative phase. Our findings suggest that in some patients with TIO, the serum phosphorus level might return to the normal range despite a relatively high postoperative serum FGF-23 level. These patients should be kept under close observation and regularly surveyed for any evidence of a residual tumor.

Low-dose adefovir dipivoxil-induced hypophosphatemia osteomalacia in five chronic hepatitis B virus-infected patients. Is low-dose adefovir dipivoxil-induced nephrotoxicity completely reversible?

Adefovir dipivoxil (ADV) is one of the most important nucleostide analogues currently in use for the treatment of chronic hepatitis B virus (HBV) infection. Low-dose ADV-induced nephrotoxicity in most cases was reported to be reversible after the discontinuation of ADV or by decreasing the dose of ADV. In our study, we have 5 documented cases of low-dose ADV-induced hypophosphatemia osteomalacia with or without Fanconi syndrome which were diagnosed in our hospital between 2010 and 2017. Three patients were observed to have a full recovery after the discontinuation of ADV. Two patients had persistently elevated urine ß2-microglobulin levels and out of these two patients, one patient had persistent hypophosphatemia after the cessation of ADV. These cases illustrated that the use of low-dose ADV increased the risk of nephrotoxicity, and in some patients, low-dose ADV-induced nephrotoxicity was not completely reversible. Patients of East Asian origin, especially those with a low body mass index, were prone to a relatively higher risk of developing low-dose ADV-induced nephrotoxicity; therefore, it was worth paying attention to the side effects caused by low-dose ADV.