The phenylboronic acid azoprobe (BA-Azo)/gamma-cyclodextrin (gamma-CD) complex exhibits a selective response for D-glucose by forming a supramolecular 2:1 inclusion complex of the azoprobes with D-glucose inside the gamma-CD cavity.
Objective: We investigated whether neural stem cells (NSC) with transgenic expression of human nerve growth factor (hNGF) transplanted into the brain could offer a therapeutic option for the treatment of Alzheimer’s disease (AD). Methods: We infused okadaic acid into rat lateral ventricles to establish a chronic AD animal model. In addition, NSC were stably transduced with hNGF and enhanced green fluorescent protein (eGFP) genes (NSC-hNGF-eGFP) by using a recombination adeno-associated virus serotype 2 (rAAV2) vector. These genetically modified stem cells were grafted into the cerebral cortex of AD rats. Results: AD model rats showed significant damage in learning and memory function, with the formation of senile plaques and neurofibrillary tangles in the cerebral cortex. The transferred hNGF gene conferred stable and high levels of protein expression in NSC in vitro. Moreover, the NSC-hNGF-eGFP, but not the NSC, survived, integrating into the host brain and enhancing cognitive performance after transplantation. Conclusion: The injection of okadaic acid into rat lateral ventricles constitutes a promising animal model for investigating selective aspects of AD. rAAV2-mediated hNGF delivery can render long-term and stable transduction of hNGF in NSC. NSC-hNGF-eGFP transplantation may offer a viable therapeutic approach for treatment of AD.
Objective: We examined the effects of low-intensity pulsed ultrasound (LIPUS) on cell differentiation, bone mineralized nodule formation and core-binding factor A1 (Cbfa1) expression in a normal human osteoblast (NHOst) cell line and bone formation in an osteoporosis animal model. Methods: NHOst cells were cultured in vitro in medium with or without LIPUS stimulation. The ultrasound stimulation frequency was 1.0 MHz at an intensity of 30 mW/cm2 for 20 min. Rats were divided into a sham-operated group (Sham) and an ovariectomized group (OVX). The right femur was treated with LIPUS (Sham-LIPUS and OVX-LIPUS) and the left femur was left untreated (Sham-CON and OVX-CON). Results: LIPUS stimulation accelerated bone nodule formation and enhanced alkaline phosphatase activity. The expression levels of Cbfa1 decreased and calcification occurred earlier and more frequently in the LIPUS than in the CON groups. The wet weight of the femur increased in OVX rats with LIPUS stimulation. Morphological images showed an increase in trabecular spongiosa in the OVX-LIPUS group. Conclusion: LIPUS accelerated osteogenesis. Moreover, since LIPUS prevents bone loss, it may be a promising treatment for osteoporosis.
Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab.A 44-year-old woman, who had no special medical history or familial history of TMAs, was admitted on suspicion of septic shock. Physical examination revealed gangrene on her soles. Blood tests revealed a decreased platelet count, disseminated intravascular coagulation (DIC), renal dysfunction, hemolysis, and infection. Although the coagulation disorder improved with intensive care, the low platelet count, elevated lactate dehydrogenase levels, and renal dysfunction persisted. Our investigations subsequently excluded thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-induced HUS. Plasma exchange only improved lactate dehydrogenase levels. We clinically diagnosed this case as atypical HUS and started eculizumab treatment. The patient's platelet count increased, her renal dysfunction improved, and the gangrene on her feet was ameliorated. The patient was discharged without maintenance dialysis therapy after approximately 3 months. Subsequent tests revealed elevated serum levels of soluble C5b-9, and genetic testing revealed compound heterozygous c.184G > A (Val62Ile) and c.1204T > C (Tyr402His) single-nucleotide polymorphisms in complement factor H.We encountered a case of complement-mediated TMA accompanied by DIC, which was successfully treated with eculizumab. Further studies are necessary to support the optimal use of eculizumab for TMA with background diseases.
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