A Female Patient With a Urinary Tract Infection and Multiple Vaginal Ulcers.

This report is to describe a rare case of urinary tract infection (UTI) with multiple vaginal ulcers. In the report, the 45-year-old female patient was diagnosed with a UTI, but white blood cells and neutrophil are higher than reference value. A vaginal ultrasound was performed with a positive fi nding of uterine myoma and multiple painless vaginal ulcers in the vaginal wall. Also, elevated antinuclear antibodies were found. After treated with antibiotic, self-healed vaginal ulcers were observed even without topical ointment use for vaginal ulcers. In conclusion, UTIs are a common disease in females. This is a rare case of a UTI with multiple vaginal ulcers. Observation of the genital condition is necessary if a woman has a UTI. Treating the source of the UTI is necessary, and the vaginal ulcerations also require appropriate treatment and follow up.

LGK974, a PORCUPINE inhibitor, mitigates cytotoxicity in an in vitro model of Parkinson's disease by interfering with the WNT/ß-CATENIN pathway.

Paraquat (PQ) as an herbicide has been demonstrated to impair dopaminergic (DAergic) neurons and highly correlate with the etiology of Parkinson's disease (PD). WNT/ß-CATENIN signaling is known for the specification and neurogenesis of midbrain DAergic neurons and implicated as a therapeutic target in treating many diseases, such as cancer and degenerative diseases. LGK974, a WNT pathway inhibitor, is currently under clinical trial for patients with malignancies. Since the exact role of WNT/ß-CATENIN signaling in mediating PD is undetermined, LGK974 was used to examine its effect on the PQ-induced cell model of PD. LGK974 attenuated PQ-induced apoptosis and released mitochondrial pro-poptotic molecules in human neuroblastoma SH-SY5Y cell. PQ increased the levels of ß-CATENIN, non-phosphorylated (Ser33/37/Thr41) ß-CATENIN, and phosphorylated glycogen synthase kinase (GSK)-3α/ß. PQ also increased the nuclear translocation of ß-CATENIN, which can be attenuated by LKG974. Furthermore, LGK974 attenuated the PQ-induced release of mitochondrial proapoptotic factors and WNT agonist 1-induced cell death. Taken together, we have shown for the first time that LGK974 mediated through the WNT/ß-CATENIN pathway to prevent PQ-induced cell death.

The role of ribosylated-BSA in regulating PC12 cell viability.

Glycation, one of the post-translational modifications, is known to influence protein structure and biological function. Advanced glycation end products (AGEs) have been shown to cause pathologies of diabetes. Glycation levels in patients with Alzheimer's disease (AD) are higher than in normal people. However, whether the glycation of susceptible proteins is a triggering event for cell damage or simply a result remains to be elucidated. In this study, we demonstrated that ribose-conjugated BSA (Rib-BSA) directly induces PC12 cell death in a dose- and time-dependent manner. The IC(50) is 4.6 µM. Unlike glucose-incubated BSA, Rib-BSA rapidly forms cytotoxic AGEs. PC12 is vulnerable to Rib-BSA. However, fructose can induce AGE formation, although no effect on cell survival was observed. This effect of Rib-BSA is reversed by pretreatment of pioglitazone and rosiglitazone, which belongs to thiazolidinediones (TZDs) and are peroxisome proliferator-activated receptor (PPAR-γ) ligands. Moreover, Rib-BSA upregulates inducible nitric oxide synthase (iNOS), cycloxygenase 2 (COX-2) expression, and p-38 phosphorylation and leaves extracellular regulated protein1/2 (ERK1/2) phosphorylation unchanged. The Rib-BSA-induced signaling changes are blocked by rosiglitazone and confirmed by PPAR-γ small-interfering RNA transfection. The reduction of cell survival by Rib-BSA is blocked by the iNOS inhibitor and p38 inhibitor. No effect on cell survival was observed using the COX-2 inhibitor. Consequently, these results show that Rib-BSA directly inducing PC12 cell death is a triggering event and TZDs protect PC12 cell from Rib-BSA damage. Signaling molecules, such as PPAR-γ, P38, and iNOS, are involved in Rib-BSA-mediated cytotoxicity.

Effect of docosahexaenoic acid on hypoxia/reoxygenation injury in human coronary arterial smooth muscle cells.

PURPOSE: Hypoxia and reoxygenation (H/R) occur in a wide variety of important clinical conditions such as myocardial infarction. H/R injury is a complex phenomenon involving not only intracellular damage processes but also an injurious inflammatory response. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has long been proved to be protective against several types of cardiovascular disease. However, its beneficial effect during H/R is inconclusive. In this study, we employed an in vitro model to examine whether DHA is protective against H/R-induced cell damage in human coronary artery smooth muscle cells (HCASMCs). METHODS: HCASMCs in the absence or presence of DHA (1, 3, 10, and 30 µM) were subjected to control or H/R treatment using a modular incubator chamber to create hypoxic condition. Cell viability was evaluated by MTT assay. Spectrophotometric and spectrofluorometric assays were used to measure the generation of nitric oxide (NO) and reactive oxygen species (ROS), respectively. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Intracellular calcium mobilization was estimated microfluorimetrically using calcium indicator dye, fura 2-acetomethyl ester. RESULTS: Hypoxia/reoxygenation caused significant injury in cultured HCASMCs. DHA at low concentrations (1, 3, and 10 µM) did not afford protection, whereas at 30 µM, it caused deleterious effects, presumably by enhancing the production of NO, ROS, IL-1ß, and IL-6 and altering the intracellular calcium dynamics. CONCLUSIONS: Our results do not support the protective function of DHA in H/R-injured coronary arterial smooth muscle cells.

Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A2A receptor and ubiquitin proteasome system.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. AIM OF THE STUDY: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). MATERIALS AND METHODS: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. RESULTS: This protection of Gastrodia elata could be blocked by an A(2A)-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A(2A)-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A(2A)-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. CONCLUSION: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A(2A)-R through PKA-dependent pathway.