An increase in the level of polycythemia rubra vera -1 (PRV-1) mRNA has been reported in some myeloproliferative disorders. We have studied the effects of PRV-1 on cell proliferation and cell survival. In cell growth assays, the number of heterologous cells expressing PRV-1 increased faster than sham-transfected cells, a difference that was more pronounced in serum-free media. Even after 5 days of exposure to serum-free media, cells expressing PRV-1 continued to proliferate, whereas the control cells ceased to proliferate. We conclude that PRV-1 is a pro-proliferation molecule, and hypothesize that its overexpression may have a role in the pathogenesis of myeloproliferative disorders.Read more
The study aimed to generate a mouse line with green fluorescent protein (GFP) specifically expressed in male germ cells to assess testicular toxicity.
The mouse line with GFP specifically expressed in male germ cells was generated by mating a germ cell-specific transgenic Cre male mouse with a double-fluorescent reporter female mouse using Cre/loxP. The mouse line was administered ethylene glycol monomethyl ether (EGME) by oral gavage. Then, the green fluorescence intensity in the testes was used as an indicator to examine the potential for testicular toxicity testing by molecular biology, histopathology, and in vivo imaging techniques.
Specific testicular GFP expression was observed in mice. GFP was mainly expressed in the germ cell lineage and concentrated in secondary spermatocytes/spermatocytes and spermatozoa. After administration of EGME, at the organ level, the green fluorescent intensity of the testes was decreased by 11 days and had disappeared by 34 days. Frozen testicular sections stained with DAPI showed significantly decreased green fluorescence in secondary spermatocytes and sperm cells. These observations were consistent with the testis weight and results of testicular histopathology.
With the application of in vivo imaging becoming popular, this mouse line with GFP specifically expressed in the male germ cells may have some advantages for the study of reproductive toxicity.Read more
Down-regulating human telomerase reverse transcriptase (hTERT) expression will significantly suppress the cell viability of laryngeal squamous cell carcinoma Hep-2, which was mainly due to the inhibition of cyclin D1 and thus G1/S phase transition.
Small-interfering RNA (siRNA) targeting hTERT can arrest the cell cycle of cancer cells, as well as inhibit telomerase activity and cell viability. However, the precise mechanisms still remain unclear. Here, we investigate the regulatory role of hTERT in cyclin D1 in laryngeal squamous carcinoma.
Short hairpin RNAs (shRNAs) specifically targeting hTERT were constructed and expressed in Hep-2 cells. Cell proliferation was measured by CCK-8 assay. Expression of hTERT, cyclin D1, cyclin E, c-myc, and GAPDH was detected by RT-PCR and Western blot; cyclin D1 and hTERT proteins in laryngeal squamous carcinoma tissue microarray were analyzed by quantum dots immunofluorescence.
hTERT silence by shRNAs decreased the proliferation of Hep-2 cells by 76.8% at day 4 (96 h). Furthermore, transfection with hTERT shRNA for 48 h also significantly reduced expression of hTERT, cyclin D1, and c-Myc, but not cyclin E. Quantum dots immunofluorescence analysis of 36 laryngeal squamous carcinoma tissue samples found that hTERT expression was highly correlated with cyclin D1 expression.Read more
During the resolution phase of hepatic fibrosis, a crucial mechanism is the apoptosis of activated hepatic stellate cells (HSCs). It is necessary to find more anti-fibrosis drugs that would modulate HSCs to be more susceptible to apoptotic stimuli. Here we showed that A771726, the active metabolite of leflunomide, markedly enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in the human hepatic stellate cell line LX-2. A771726 could increase caspase activity in LX-2 cells in a dose-dependent manner. A771726 did not increase the expression of TRAIL receptors in LX-2 cells but could inhibit activation of the c-Jun NH2-terminal kinase (JNK) pathway through decreasing TRAIL-induced JNK and c-Jun phosphorylation. Moreover, A771726 could accelerate TRAIL-induced apoptosis via inhibiting nuclear factor-kappaB (NF-kappaB) activation in LX-2 cells. In conclusion, our results indicated leflunomide could enhance the sensitivity of LX-2 cells to TRAIL-induced apoptosis via inhibiting the survival pathways and provided a promising approach to anti-fibrotic therapy with leflunomide.Read more
The dynamics of a combustion reaction, namely, O((3)P) + CH4 → OH + CH3, is investigated with an eight-dimensional quantum model that includes representatives of all vibrational modes of CH4 and with a full-dimensional quasi-classical trajectory (QCT) method. The calculated excitation functions for the ground vibrational state CH4 agree well with experiment. Both quantum and QCT results suggest that excitation of the stretching modes of CH4 enhances the reaction, while the bending and umbrella modes have a smaller impact on reactivity, again consistent with experimental findings. However, none of the vibrational excitations has comparable efficiency in promoting the reaction as translational energy.Read more
We demonstrate a highly tunable photonic bandgap fiber, which has a large-core diameter of 25 microm and an effective mode area of 440 microm2. The tunability is achieved by infiltrating the air holes of a photonic crystal fiber with an optimized liquid-crystal mixture having a large temperature gradient of the refractive indices at room temperature. A bandgap tuning sensitivity of 27 nm/degrees C is achieved at room temperature. The insertion loss is estimated to be less than 0.5 dB and caused mainly by coupling loss between the index-guided mode and the bandgap-guided mode.Read more
Erythroderma is a rare skin disorder and studies on its causes and prognosis are rare in the literature.
We reviewed the clinical, laboratory and biopsy materials of 260 patients diagnosed with erythroderma who were treated in our department over an 11-year period. Patients were followed up to better understand the evolution of erythroderma.
This study was performed at our hospital between January 2001 and 2012 and included 260 patients with erythroderma. We recorded epidemio-clinical, biological and histological data, treatments and outcomes. Clinical-histological correlation was analyzed. Overall survival and relapse-free survival for a limited number of etiologies were described using Kaplan-Meier estimates.
The mean age at onset in this study was 52.57 ± 17.94 (SD) years (range 13-87), with a male-to-female ratio of 3:1. Acute onset was present in 15.38% of patients. Clinical findings were dominated by pruritus (87.69%), fever (40%), edema (37.69%), chills (31.15%), nail changes (29.62%), weakness (19.23%), lymphadenopathy (19.23%), weight loss (14.62%) and islands of normal skin (13.46%). Skin biopsies revealed the cause in 55.56% (65/117) of the patients. The most common causative factors were pre-existing dermatoses (70.77%), followed by idiopathic causes (14.23%), drug reactions (12.69%) and malignancies (2.31%). Among the pre-existing dermatoses, psoriasis was the most common etiology (143/260, 55%). In the drug-induced group, carbamazepine was the most frequently implicated drug in our study (33.33%). Chinese traditional herbal medicines are among the causes of drug-induced erythroderma as well. We also found that Langerhans cell histiocytosis, tongue cancer, hypereosinophilic syndrome, bullous pemphigoid and dermatomyositis could be causes of erythroderma. From our follow-up study, 39 (31.2%) of the 125 patients from whom information was available had relapsed. The patients with idiopathic erythroderma had a higher relapse rate. Of the 5 patients who died, 4 deaths were directly related to erythroderma.
Most of the clinical features of erythroderma are unspecific with few cause-orienting clues. Although numerous laboratory values were abnormal, most findings were nondiagnostic and were related to the inflammatory process, except for skin biopsy. Our study had a high percentage of erythroderma secondary to pre-existing dermatoses and a low percentage of malignancy patients. Repeated evaluations, close follow-up and biopsy are recommended.Read more
When given prior to brain ischemia, mitochondrial division inhibitor-1 (mdivi-1) attenuates the brain damage caused by ischemia. Here, we investigated the potential effects of post-ischemia mdivi-1 treatment (1mg/kg, i.p., administered immediately after 2h of ischemia and prior to reperfusion) using a MCAO rat model. Mdivi-1 treatment decreased infarct volume and improved neurological function. In addition, cytochrome C release was attenuated, and neuronal apoptosis was decreased. The mitochondrial fission protein dynamin-related protein 1 (Drp1) was decreased in the mitochondrial fraction but increased in the cytosolic fraction. Mdivi-1 treatment augmented the increases in the mRNA expression of peroxisome proliferator-activated receptor coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcriptional factor A. In conclusion, when given after ischemia and prior to reperfusion, mdivi-1 can protect against brain damage by inhibiting the mitochondria-mediated apoptosis induced by mitochondrial fission. Post-ischemia mdivi-1 treatment might promote I/R-induced mitochondrial biogenesis.Read more
A sensitive and reliable HPLC coupled with diode array detection and MS method was developed and validated for the first time to simultaneously identify and quantify eight characteristic 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones (THPECs) in Chinese eaglewood. Chromatographic separation was performed on a Zorbax SB C18 column with a gradient of acetonitrile/0.1% formic acid/water as the mobile phase. The MS fragmentation behavior of THPECs was characterized as the successive neutral loss of two molecules of H2 O ([M+H-18-18](+) ) and then two molecules of CO ([M+H-18-18-28-28](+) ), which could be used to differentiate Chinese eaglewood from counterfeits. Validation of the developed analytical method showed good linearity, satisfactory precision, and good recovery. The established method was successfully applied to the simultaneous determination of eight THPECs in ten batches of Chinese eaglewood, which could be used as a tool for the quality control of Chinese eaglewood.Read more