Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review

Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy

NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression

Background/Aims: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. Methods: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. Results: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1β, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-κB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-κB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-κB activation. Conclusion: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Effect of phosphoglucosamine mutase on biofilm formation and antimicrobial susceptibilities in M. smegmatis glmM gene knockdown strain.

UDP-N-acetylglucosamine (UDP-GlcNAc) is a direct glycosyl donor of linker unit (L-Rhamnose-D-GlcNAc) and an essential precursor of peptidoglycan in mycobacteria. Phosphoglucosamine mutase (GlmM) is involved in the formation of glucosamine-1-phosphate from glucosamine-6-phosphate, the second step in UDP-GlcNAc biosynthetic pathway. We have demonstrated that GlmM protein is essential for the growth of M. smegmatis. To facilitate the analysis of the GlmM protein function in mycobacteria, a tetracycline inducible M. smegmatis glmM gene knockdown strain was constructed by using an antisense RNA technology. After induction with 20 ng/ml tetracycline, the expression of GlmM protein in glmM gene knockdown strain was significantly decreased, resulting in a decline of cell growth. The morphological changes of glmM gene knockdown strain induced with 20 ng/ml tetracycline have been observed by scanning electron microscope and transmission electron microscope. Furthermore, insufficient GlmM protein reduced the biofilm formation and increased the sensitivity to isoniazid and ethambutol in M. smegmatis, indicating that GlmM protein had effect on the biofilm formation and the senstivity to some anti-tuberculosis drugs targeting the cell wall. These results provide a new insight on GlmM functions in mycobacteria, suggesting that GlmM could be a potential target for development of new anti-tuberculosis drug

Preparation and characterization of a new reference standard GSB-Mg for Mg isotopic analysis

We have prepared a large volume of pure, concentrated and homogeneous magnesium standard solution (GSB-Mg) to be used as a secondary reference standard by the magnesium isotope community. This new standard solution can also be used for quality assurance, including the development and validation of analytical procedures, preparation and test of analytical methods, quality control and training of analysts. The delta Mg-26 values relative to DSM3, measured by multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), are -2.038 +/- 0.027 parts per thousand (n= 45, Lab 1), -2.024 +/- 0.055 parts per thousand (n= 7, Lab 2), -2.078 +/- 0.081 parts per thousand (n= 6, Lab 3), -2.037 +/- 0.015 parts per thousand (n= 8, Lab 4), and -2.067 +/- 0.039 parts per thousand (n= 12, Lab 5). The delta Mg-26 and delta Mg-25 values for the GSB-Mg standard solution are -2.049 parts per thousand and -1.056 parts per thousand, with a combined expanded (k= 2) uncertainty of 0.049 parts per thousand and 0.028 parts per thousand, respectively. These values show higher similarity to Mg isotopic compositions of carbonates and marine sediments compared to those of the mantle and crustal rocks, making the GSB-Mg solution a great reference material for Mg isotopic analysis of carbonates and marine sediments.</p

Transmission electron micrographs of wild type mc²155 strain and <i>M. smegmatis</i> AS strain.

<p>Bacterial cells with or without tetracycline were incubated at 37°C for 36 h and harvested respectively TEM observation (A–D). A, C. <i>M. smegmatis</i> AS strain without tetracycline (15000× and 60000×); B, D. <i>M. smegmatis</i> AS strain induced with 20 ng/ml tetracycline (15000× and 60000×).</p

Scanning electron micrographs of wild type mc²155 strain and <i>M. smegmatis</i> AS strain.

<p>Bacterial cells with or without tetracycline were incubated at 37°C for 36 h and harvested respectively for SEM (A–E). A. wild type mc²155 strain induced with 20 ng/ml tetracycline (10000×); B, C. <i>M. smegmatis</i> AS strain without tetracycline (10000× and 20000×); D, E. <i>M. smegmatis</i> AS strain with 20 ng/ml tetracycline (10000× and 20000×).</p

Bacterial growth of wild type mc²155 strain and <i>M. smegmatis</i> AS strain.

<p>The cultures were grown in LB broth containing 0.05% Tween 80 at 37°C with different concentration of tetracycline. The OD600 and CFU of the cultures were monitored at interval of 12 h. A. Growth curve of the wild type mc²155 strain; B. Growth curve of the <i>M. smegmatis</i> AS strain; C. CFU of the wild type mc²155 strain; D. CFU of the <i>M. smegmatis</i> AS strain. (▴) The cultures without tetracycline; (▪) The cultures induced with 10 ng/ml tetracycline; (○) The cultures induced with 20 ng/ml tetracycline; (•) The cultures induced with 30 ng/ml tetracycline; (□) The cultures induced with 50 ng/ml tetracycline. The values plotted are the mean value and standard deviation from triplicate experiments.</p