Anthocyanins from Malus spp. inhibit the activity of Gymnosporangium yamadae by downregulating the expression of WSC, RLM1, and PMA1.

Malus plants are frequently devastated by the apple rust caused by Gymnosporangium yamadae Miyabe. When rust occurs, most Malus spp. and cultivars produce yellow spots, which are more severe, whereas a few cultivars accumulate anthocyanins around rust spots, forming red spots that inhibit the expansion of the affected area and might confer rust resistance. Inoculation experiments showed that Malus spp. with red spots had a significantly lower rust severity. Compared with M. micromalus, M. 'Profusion', with red spots, accumulated more anthocyanins. Anthocyanins exhibited concentration-dependent antifungal activity against G. yamadae by inhibiting teliospores germination. Morphological observations and the leakage of teliospores intracellular contents evidenced that anthocyanins destroyed cell integrity. Transcriptome data of anthocyanins-treated teliospores showed that differentially expressed genes were enriched in cell wall and membrane metabolism-related pathways. Obvious cell atrophy in periodical cells and aeciospores was observed at the rust spots of M. 'Profusion'. Moreover, WSC, RLM1, and PMA1 in the cell wall and membrane metabolic pathways were progressively downregulated with increasing anthocyanins content, both in the in vitro treatment and in Malus spp. Our results suggest that anthocyanins play an anti-rust role by downregulating the expression of WSC, RLM1, and PMA1 to destroy the cell integrity of G. yamadae.

Case Report: Cystinosis in a Chinese Child With a Novel CTNS Pathogenic Variant.

Objective: To report a rare case of cystinosis with a novel CTNS pathogenic variant in the Chinese population. Methods: Retrospective analysis of the clinical manifestations, laboratory results, and gene detection data of a child with cystinosis. Results: A Chinese Zang ethnic girl could not stand or walk until 3 years old, with additional symptoms including a loss of appetite. Since then, the girl gradually exhibited "X" leg, double wrist joints, a bilateral ankle deformity, and rickets. At the age of 9 years, the girl was hospitalized. Laboratory testing showed that her blood phosphorus, blood calcium and blood potassium levels were significantly decreased. At the same time, the girl's urine glucose and urine protein were positive, although her fasting blood glucose, glycosylated hemoglobin, and 75 g glucose tolerance were not significantly abnormal. Further, blood gas analysis showed metabolic acidosis. These symptoms corresponded to Fanconi syndrome. Gene analysis showed that there was a homozygous pathogenic variant c.140 ≤ 5G > A (p.?) in the CTNS gene, which was a small variation in the intron region. To our knowledge, this is the first report of the rare variant. Conclusion: Attention should be paid to the differential diagnosis of cystinosis by gene analysis in children whose clinical manifestations include exercise dysplasia, renal damage, or multiple organ damage (including bone, thyroid, etc) and who cannot be firmly diagnosed for the time being.

Crumbs homolog 2 mutation in two siblings with steroid-resistant nephrotic syndrome: Two case reports.

BACKGROUND: Crumbs homolog 2 (CRB2) is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes; mutations can directly lead to steroid-resistant nephrotic syndrome (SRNS). However, the characteristics of nephrotic syndrome (NS) caused by CRB2 mutations have not been described. CASE SUMMARY: We report a novel compound heterozygous mutation of the CRB2 gene in two siblings with SRNS. The two siblings had edema, proteinuria, hypoproteinemia and hyperlipidemia. Both their father and mother had normal phenotypes (no history of NS). Whole exon sequencing (WES) of the family showed a novel compound heterozygous mutation, c.2290 (exon 8) C > T and c.3613 (exon 12) G > A. Glucocorticoid therapy (methylprednisolone pulse therapy or oral prednisone) and immunosuppressive agents (tacrolimus) had no effect. During a 3-year follow-up after genetic diagnosis by WES, proteinuria persisted, but the patient was healthy. CONCLUSION: CRB2 mutations related to SRNS often occur in exons 7, 10, and 12. Clinical manifestations of SRNS caused by CRB2 mutations are often less severe than in other forms of SRNS.

A child with recurrent pyogenic arthritis with the PSTPIP1 mutation.

Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome is a rare disease, linked to an auto-inflammatory pathway. We report a 7-year-old boy with recurrent suppurative knee arthritis without signs of suppurative skin infection or ulcer; his younger brother had the same symptom. Genetic testing indicated the presence of proline-serine-threonine phosphatase interacting protein 1 gene mutation in both boys. Our patient's grandfather had a history of recurrent pyoderma, and his father though a genetic carrier had no symptoms. Interestingly, our patient displayed markedly high levels of interleukin-6, while interleukin-1 and other cytokines were not elevated. These lab findings led to the treatment of pyogenic arthritis, pyoderma gangrenosum, and acne syndrome with tocilizumab. Previously reported cases of similar phenotypes of the syndrome have not presented in this fashion, nor have there been reported cases of pyogenic arthritis, pyoderma gangrenosum, and acne syndrome with a positive family history and an elevation in interleukin-6. The mutation site of proline-serine-threonine phosphatase interacting protein 1 in this incomplete pyogenic arthritis, pyoderma gangrenosum, and acne syndrome has not been reported before. It is possible that there are other pathogenic ways to trigger these auto-inflammatory disorders. Tocilizumab, which specifically targets interleukin-6, was effective in this case.

Colour Doppler and Biomarkers Utility for Renal Damage due to Congenital Hydronephrosis.

OBJECTIVE: To determine colour doppler and serum biomarkers spectrum in children with congenital hydronephrosis. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Pediatric Nephrology, West China 2nd University Hospital of Sichuan University and Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), China, from January to December 2017. METHODOLOGY: A total of 95 children with hydronephrosis were selected as case group. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group. Forty children with normal renal function were selected as normal comparison group. Peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistance index (RI), pulsatility index (PI), and serum cystatin C (CysC), ß2-microglobulin (ß2-MG), and 1-microglobulin (ß1-MG) of all subjects in both groups were recorded and compared. RESULTS: The Vmax, Vmax of main renal artery (MRA) and interlobar renal artery (IRA) in case group were lower than those of normal group (all p<0.001). RI of MRA and IRA in case group were higher than those of normal control group (both p<0.001). There were no significant differences in the PI of MRA and IRA between the two groups (p=0.700, and 0.250 respectively). The levels of serum CysC, ß2-MG and α1-MG in normal control group, mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group were significantly different (all p<0.001), and the levels of serum CysC, ß2-MG, α1-MG were also different in children with different degrees of hydronephrosis. CONCLUSION: Combined detection of colour doppler and serum biomarkers CysC, ß2-MG and α1-MG in the diagnosis of renal damage in congenital hydronephrosis is feasible and reliable.

Synthesis and Application of Water-Soluble Oxazine Dyes for Detection of PHAs-Producing Bacteria.

Derivatives of oxazine dyes were synthesized on mulitigram scales via efficient synthetic strategies. One practical route was selected to prepare compounds 6, 9 and 10, especially water-soluble compound 6 was obtained in better yield than reported, and compound 10 was insoluble in aqueous media in absence of phenolic-OH. Compounds 3 and 9 were found to be clear pH-dependent between pH = 4.0 and 10.0, and could be used as acid-base indicators to measure intracellular pH. Compounds 6, 9, 10 all have carboxylic acid functionalities, which could be activated and used to conjugate the dyes to biomolecules. In addition, compounds 6 and 9 with good solubility in aqueous media were used to develop a simple, quick, safe, highly sensitive staining method to detect PHAs-producing bacteria on heat-fixed smears, which was confirmed by fluorescence images of PHAs granules of bacteria.

Children with Steroid-resistant Nephrotic Syndrome: Long-term Outcomes of Sequential Steroid Therapy.

OBJECTIVE: This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome (SRNS), who received methylprednisolone pulse therapy (MPT)-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. METHODS: We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. RESULTS: Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five (55.6%) achieved complete or partial remission, 19 (30.2%) of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children (77.8%) experienced relapses, of whom 31 (49.2%) demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients (7.9%) complained of vomiting or nausea during MPT infusion; 25 (39.7%) experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 (41.3%) had poor growth associated with long-term steroid use. Twenty-eight patients (44.4%) failed to respond to MPT, of whom 21 (33.3%) achieved complete or partial remission with immunosuppressive agents. CONCLUSION: MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.

The relationship between children kidney diseases and adult ESRD--an epidemiological investigation of 700 cases.

BACKGROUND: We planned an epidemic investigation of 700 cases who suffered from chronic renal failure (CRF) to search for the evidence to demonstrate the relationship between children kidney diseases and adult CRF. METHODS: Seven hundred patients from four hospitals in Chengdu, China, were investigated face-to-face to complete a questionnaire referring to the information of diagnoses, treatment, history and so on. These enumeration count data were analyzed by statistical description. RESULTS: In 700 patients, there were 402 male and 298 female including 21 children and 679 adults. In the disease spectrum, the unclear accounted for 36.3% of totality. Chronic glomerulonephritis made the top proportion (14.4%) in primary kidney diseases. Diabetic nephropathy (15.3%), hypertensive nephropathy (10.1%), and gouty nephropathy (6%) made the primary proportion in secondary kidney diseases. In 21 children, chronic glomerulonephritis had the highest proportion of 52.4%, followed by nephrotic syndrome (19%), Henoch-Schönlein purpura (9.5%), and urinary tract obstruction (4.8%). Thirty-eight cases developed into kidney diseases during childhood including 21 children mentioned above, in which 17 cases presented CRF in the adult stage. The primary renal diseases are chronic glomerulonephritis (60.5%), purpura nephritis (18.4%), nephrotic syndrome (10.5%), urinary tract obstruction (2.6%), and the unclear (7.9%). CONCLUSION: The survey showed that there were a high proportion of patients whose causes were unknown, to which attention should be paid. Chronic glomerulonephritis remained the main cause of CRF no matter whether in children or in adults. Purpura during childhood, used to be thought as self-limited, might eventually develop into CRF in adulthood, which caught our eyes.

[Activation of TLR3 pathway in the pathogenesis of nephrotic syndrome induced by respiratory syncytial virus in rat model].

OBJECTIVE: To explore the activation of toll-like receptor 3 (TLR3) pathway on the process of respiratory syncytial virus (RSV) induced nephropathy. METHODS: SD rats were inoculated intranasally and intraperitoneally with 6 X 10(6) plaque forming unit(PFU) RSV and sacrificed on days 4, 14, 30 postinoculation (RSV4, RSV14 and RSV30). The normal rats without intervention were set as control. Renal tissues were obtained, and the morphological changes were studied. The expressions of TLR3, NF-kappaB and IL-13 in the rats' kidney were measured with real-time quantitative RT-PCR, and indirect IF staining. RESULTS: After the inoculation of RSV, the rats had proteinuria and the fusion of foot processes of glomerular epithelial cells, resembling human minimal changed nephrotic syndrome (MCNS). The expressions of TLR3, NF-kappaB and IL-13 in renal tissues increased obviously at Day 4 and Day 14 postinoculation, the differences were significant when compared with normal control rats (P < 0.05). The expressions of these three factors decreased at Day 30, which were not significantly different to those of normal control group (P > 0.05). CONCLUSION: TLR3 signal pathway may play an important role in early stage of RSV nephropathy.

[Expression of glomerular heparan sulfate domains in pediatric patients with minimal change nephrotic syndrome].

OBJECTIVES: To investigate the expression of glomerular heparin sulfate (HS) in paediatric patients with minimal change nephritic syndrome (MCNS). METHODS: The kidyney tissues were collected by biopsy from 13 paediatric patients with MCNS, while 5 normal renal biopsy samples were used as control. HS in glomeruli was analysed by indirect immunofluorescence staining using four different monoclonal antibodies, Hepss1, 3G10, JM403 and 10E4, which all recognize distinct HS species and each interacts with a specific HS domain. The concentrations of urine heparan sulfate also were measured by enzyme-linked immunosorbent assay (Elisa). RESULTS: Expression of HS fine domains was aberrant in paediatric patients compared with control subjects. Children with MCNS in replase showed a decreased glomerular expression of 10E4, JM403 and Hepss1 (P < 0.05). The level of urinary HS was significantly increased in peadiatric patients with MCNS when compared with that in control subjects (P < 0.01). CONCLUSION: These results suggest that loss of heparan sulphate in renal tissue may play a role in the pathogenesis of MCNS proteinuria.