Renal Manifestation in Scrub Typhus during a Major Outbreak in Central Nepal.

Renal involvement and acute kidney injury (AKI) are common clinical manifestations seen in scrub typhus, a vector-borne tropical disease. There are no data on renal manifestation in scrub typhus in Nepal. We conducted a prospective study to analyze the incidence, urinary abnormalities, course, severity, outcome, and the predictors of AKI in patients with scrub typhus during a major outbreak in Central Nepal. Total 1398 patients admitted with acute febrile illness were subjected for Scrub Typhus Detect™ Immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) test, of which 502 (35.90%) patients tested positive and were included in the study. Mean age of the patients was 30.37 ± 18.81 years (range, 1-79 years) with 26.29% in the pediatric age group. Female-to-male ratio was 1.26:1. Mean duration of fever was 6.8 ± 3.1 days. Mean IgM ELISA value for scrub typhus was 2.17 ± 1.70 without difference in AKI and non-AKI groups (2.17 ± 1.76 vs. 2.16 ± 1.62; P = 0.94). Urinary abnormalities were seen in 42.3% of patients. Mean serum creatinine was 1.37 ± 0.69 mg/dl with significant difference in two groups (1.85 ± 0.87 vs. 1.03 ± 0.17; P = 0.003). AKI was seen in 35.8% of patients with majority having Stage 1 AKI (68.3%) followed by Stage 2 (34.1%) and Stage 3 (1.2%). Hemodialysis was required for 3.94% of patients. In 54% of patients, AKI occurred in fifth and sixth day of fever. ICU admission was required for 18.73% of patients and 8.57% required ventilator support. Mortality rate was 1.79%, which was higher among patients with AKI (2.96% vs. 1.0%; P = 0.106). Multivariate analysis revealed that the presence of pneumonia, shock, and acute respiratory distress syndrome predicted the development of AKI.

Smad4 in osteoblasts exerts a differential impact on HSC fate depending on osteoblast maturation stage.

Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4 in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1 mutants displayed senescence-associated phenotypes. OC mutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1 mutants than control littermates, suggesting potential impairment of CXCR4-CXCL12-mediated HSC retention. Disruption of the CXCR4-CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated ß-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4 in OBs differentially modulates HSC fate in a stage-dependent manner.

Gene delivery of c-myb increases bone formation surrounding oral implants.

Bone regeneration around titanium (Ti) implants is a relatively slow process. The c-myb transcription factor has been associated with high proliferation and differentiation rates in bone. This study analyzed whether c-myb can enhance new bone surrounding the implant. In vitro overexpressed chitosan-gold nanoparticles conjugated with plasmid DNA/c-myb (Ch-GNPs/c-myb)-coated Ti surfaces were associated with enhanced expression of the osteogenic molecules osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and bone morphogenetic proteins (BMP2/7) in MC-3T3E1 osteoblast cells. Further, to determine its in vivo effect, we inserted Ch-GNPs/c-myb-coated Ti implants into rat mandibles. One and 4 wks post-implantation, mandibles were examined by microcomputed tomography, immunohistochemistry, and hematoxylin & eosin staining. The microcomputed tomography analysis demonstrated that c-myb overexpression increased the density and volume of newly formed bone surrounding the implants, compared with those in controls (p < .05). Further, c-myb increased the number of cells expressing BMP2/7 and aided in the increase of new bone (p < .05). These results support the view that c-myb overexpression accelerates new bone surrounding implants and can serve as a potent molecule in promoting tissue regeneration around dental implants. The recipient rat used in this system provides an excellent in vivo model for studies of bone regeneration.

Anti-inflammatory effect of pachymic acid promotes odontoblastic differentiation via HO-1 in dental pulp cells.

OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom Formitopsis niagra is examined to determine whether it affects pulpal inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory character and odontoblast differentiation by pachymic acid were analyzed by Western blotting, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of pachymic acid via HO-1 induction, the cells were treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs treated with pachymic acid affected anti-inflammatory effect and induction of odontoblast differentiation through increasing HO-1 expression. In addition, pachymic acid has potent cytoprotection and mineralization under H2O2 treatment. Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF-κB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2) translocation into nucleus. Overall, NF-κB and Nrf2 translocation were regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti-inflammatory function and odontoblast differentiation via HO-1 pathway. These results suggested that pachymic acid may be applicable for prevention of oral inflammation or to improve dentin mineralization against several stresses.