This work describes the process by which a metabolically unstable TRT‐0002 compound exhibiting Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐sensitizing activity for Huh7 cells at a ...high working concentration (40 μM) is converted to more potent and metabolically improved analogues by modifying the 5‐amino group and the 1‐aryl moiety in the 1H‐indazole skeleton. The efforts enabled us to identify 5‐sulfonamido derivatives, TRT‐0029 and TRT‐0173 compounds, working at lower concentrations (10 and 20 μM, respectively) and with improved metabolic stabilities. As reported previously by us, co‐treating cultured Huh7 cells with either TRT‐0029 or TRT‐0173 and TRAIL resulted in TRAIL‐induced apoptosis due to the inhibition of the MKK7–TOR signaling pathway regulator‐like (TIPRL) interaction and subsequent phosphorylation of MKK7 and JNK. In addition, the injection of TRT‐0029 or TRT‐0173 compound suppressed tumor growth in combination with TRAIL in an in vivo hepatocellular carcinoma (HCC) mouse xenograft model. TRT‐0029 and TRT‐0173 compounds and the relevant structure–activity relationship can provide an insight into further study on optimization of potency and metabolic stability.
Objectives : This study was performed to evaluate the effects of water extract of Cervi Parvum Cornu(CPC), Aconiti Lateralis Radix Preparata(ALR), and Yongbu-tang(YBT) on suppression of the receptor ...activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation and bone resorption.
Methods : The effects of CPC, ALR, YBT extracts on osteoclast differentiation were determined by culture of bone marrow macrophage(BMM). The mRNA expression levels of the nuclear factor of activated T-cells cytoplasmic 1(NFATc1), c-Fos and tartrate-resistant acid phosphatase(TRAP) in BMMs were analyzed by reverse transcriptase polymerase chain reaction(RT-PCR). Similarly, the protein expression levels of NFATc1, c-Fos, mitogen-activated protein kinase(MAPK)s and β-actin in cell lysates were measured by western blotting. In addition, effects of CPC, ALR and YBT extracts were determined by means of Lipopolysaccharide(LPS)-induced bone-loss with mice.
Results : CPC, ALR and YBT extracts showed remarkable inhibition on RANKL-induced osteoclast differentiation without cytotoxicity. CPC and ALR extracts significantly reduced the protein expression level of NFATc1. YBT extract significantly reduced the mRNA expression levels of c-Fos, NFATc1 and the protein expression levels of c-Fos, NFATc1, AKT, p38, c-Jun N-terminal kinase(JNK). Further, YBT extract suppressed degradation of I-κB. And ALR extract significantly restored the bone erosion by LPS treatment in mice.
Conclusions : YBT extract showed more remarkable inhibition on osteoclast differentiation than CPC and ALR extracts in vitro. ALR extract showed remarkable inhibition on bone resorption in vivo. Thus, YBT extract can be a useful treatment for bone-loss diseases such as osteoporosis. KCI Citation Count: 1
We describe two patients with fungal keratitis refractory to standard antifungal therapy whose conditions were managed with voriconazole.
The first case is a patient with endophthalmitis and corneal ...ulcer due to Candida parapsilosis after receiving a corneal transplant. The patient was treated with amphotericin but showed no signs of improvement. Topical voriconazole, oral voriconazole, and intravitreal voriconazole yielded signs of improvement. The second case is a 63-year-old male who underwent a month of empiric treatment with 0.2% topical amphotericin for fungal keratitis but showed no signs of improvement. Treatment was then provided with 1% voriconazole. Both cases showed effective treatment with voriconazole.
Voriconazole may be considered as a new method to treat fungal keratitis refractory to standard antifungal therapy. KCI Citation Count: 4
Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression ...profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level.
We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile.
We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence.
EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT.
Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs.
We propose an enhanced Brinson model with modified kinetics for martensite transformation. Two additional material constants are considered to follow the stress-temperature diagram above austenite ...start temperature (As) along with treatment to keep the continuity of the martensite volume fraction and the path dependency of the phase transformation. To demonstrate the performance of the proposed model, we implement this algorithm into ABAQUS user subroutine, then conduct several numerical simulations and compare their results with SMA wire experiments as well as those of three-dimensional SMA constitutive models. From the results, it turns out that the proposed model is as accurate as the three-dimensional models and shows better accuracy over original Brinson model in terms of recovery stress.
Background
BORIS/CTCFL, a paralog of CTCF and member of the cancer-testicular antigen family, is abnormally activated in multiple cancers.
Objective
We investigated the relationship between ...polymorphic variants of the
BORIS
minisatellite 2 (
BORIS
-MS2), located within the 5′ upstream promoter region of
BORIS
, and bladder cancer.
Methods
We used case-control study with 516 controls and 113 bladder cancer patients. To evaluate whether minisatellite variants play a role in BORIS expression, we examined the transcript levels of a reporter gene linked to these minisatellites in cell lines. We also examined BORIS expression in cancerous and non-cancerous bladder tissue.
Results
A statistically significant association was identified between the short rare allele (13-repeat) and bladder cancer incidence (odds ratio (OR) 2.97, 95% confidence interval (CI) 1.14, 7.74; P = 0.020). In particular, short rare alleles in the younger group (aged < 65) were associated with statistically significant increase in bladder cancer risk (OR 5.38, CI 1.32, 21.87; P = 0.01). The BORIS-MS2 region acted as a negative regulator, and the expression level of the luciferase reporter in bladder cancer cells was less effectively inhibited than in normal cells. Furthermore, the expression of BORIS mRNA significantly differed (P < 0.05) between normal and cancerous muscle-invasive bladder cancer tissues, and relationship to clinical parameters was observed.
Conclusions
The short rare allele of BORIS-MS2 could be used to identify bladder cancer risk. BORIS expression levels have been shown to increase with the progression of bladder cancer, could be used as a biomarker for its progression.
Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare entity and is frequently associated with ovarian surface epithelial tumors. Since Collins et al. described the fi rst case of mixed ...neuroendocrine and mucinous carcinoma, a few more cases of primary ovarian LCNECs have been reported. The prognosis of LCNECs is generally very poor even when the diagnosis is made at an early stage. A 40-year-old woman presented with a pelvic mass measuring 30 cm in diameter. She underwent an exploratory laparotomy for resection of the pelvic mass and staging if needed. After the operation, she was diagnosed of stage Ia LCNEC associated with mucinous tumor (including benign, borderline, malignant tumor) of left ovary. The patient received six cycles of paclitaxel-carboplatin chemotherapy postoperatively. There have been no signs of local tumor recurrence or metastasis at followup examinations during the fi rst 8 months after the operation. KCI Citation Count: 0
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