Single-nucleotide polymorphisms of APE1 associated with risk and prognosis of vitiligo in a Han Chinese population.

BACKGROUND: The single-nucleotide polymorphisms (SNPs) of apurinic/apyrimidinicendonuclease 1 (APE1), which has been implicated in cancers and the DNA base excision repair (BER) process, have not been thoroughly investigated in association with the risks of oxidative stress-related vitiligo. OBJECTIVES: The aim of this study is to investigate associations between APE1 single-nucleotide polymorphisms 141T >G and 1349T >G and risk and prognosis of vitiligo. MATERIAL AND METHODS: From June 2013 to June 2015, a total of 460 vitiligo patients were randomly recruited as a case group; 200 of these patients received narrow bound ultraviolet B (NB-UVB) treatment. Meanwhile, 460 healthy controls were included as a control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to explore the distribution frequencies of genotypes. RESULTS: Significant differences were detected between the case group and the control group in the frequencies of the 141T >G and 1349T >G genotypes. At 141T >G, compared with patients carrying the TG + GG genotype, male patients carrying the TT genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Binary logistic regression analysis demonstrated that the TT genotype at 141T >G and the non-TT genotype at 1349T >G were independent risk factors for vitiligo development. At 1349T >G, compared with patients carrying the TT genotype, male patients carrying the TG + GG genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Moreover, patients carrying 141TG + GG or 1349 TT genotypes had better photochromic effects, lower cumulative radiation doses, shorter treatment times, and earlier first photochromic times.

Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway.

Skin squamous cell carcinoma (SCC) is generally considered as nonaggressive lesions and mainly caused by ultraviolet (UV) radiation. Gadd45a is a key component protecting skin against UV-induced tumors. For that, the study aims to investigate the mechanism of Gadd45a gene silencing on cell proliferation, apoptosis, and senescence in nude mice with skin SCC through the p53 signaling pathway. Healthy nude mice was collected as the normal group and 40 nude mouse models of skin SCC were successfully established as the model group, which were sub-divided into five groups. The incidence, size, and weight of SCC tumor of nude mice were observed. The mRNA expression of Gadd45a, Cyclin B1, MMP-2, Bcl-2, and Bax were determined by RT-qPCR. Cell viability, cell cycle and apoptosis, cell senescence were detected by MTT assay, flow cytometry, and ß-galactosidase staining, respectively. The levels of inflammatory factors and vascular endothelial growth factor (VEGF) were detected by using ELISA. The protein expression rate of mutant p53 was detected by immunohistochemistry. Mice transfected with siGadd45a showed increased tumor incidence, size, and weight. Cells transfected with siGadd45a showed decrease in expression of Gadd45a and Bax; and increase in expression of Cyclin B1, MMP-2, and Bcl-2, expression of mutant p53, IL-1α, IL-1ß, IL-6, TNF-α, and VEGF. Cell apoptosis and senescence were inhibited, while cell viability and proliferation were promoted after siGadd45a treatment. The results reveal that Gadd45a silencing increases tumor cell proliferation and reduces apoptosis and senescence through the p53 signaling pathway in skin SCC.

Chikusetsu (CHI) triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species (ROS) production.

The prostate cancer prognosis is still not fully understood. Chikusetsu saponin Iva (CHI), isolated from Aralia taibaiensis, shows anti-cancer and anti-inflammatory properties. Here, in our study, we attempted to explore the efficiency and the possible molecular mechanism by which CHI may suppress prostate cancer. CHI was found to inhibit prostate cancer cell proliferation and induce cell death without cytotoxicity in prostate normal cells. CHI resulted in intracellular reactive oxygen species (ROS) production, and induced apoptosis regulated by mitochondria in vitro studies. CHI-caused apoptosis was shown in both caspase-dependent and -independent manner, which released cyto-c, enhancing caspases expression and promoting apoptosis-inducing factors (AIF) as well as endonuclease G (Endo G) nuclear transfer, respectively. Moreover, in vivo study showed that prostate tumor was inhibited by CHI administration through apoptosis induction. Thus, the results illustrated that CHI might be an effective therapeutic strategy for prostate cancer treatment in future.

Haptoglobin protein and mRNA expression in psoriasis and its clinical significance.

The present study aimed to explore the association between haptoglobin protein and mRNA expression and psoriasis. A total of 138 patients with psoriasis that were undergoing therapy at Linyi People's Hospital (Linyi, China) between January 2011 and January 2015 were enrolled in the present study. The mRNA expression levels of haptoglobin were detected by in situ hybridization; immunohistochemistry was used to detect haptoglobin protein expression; and double­labeling immunofluorescence was used to count Langerhans cells; western blotting was also conducted to determine protein expression. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of haptoglobin for psoriasis. Compared with the normal and negative control (NC) groups, the mRNA expression levels of haptoglobin were markedly increased in the experimental group (P<0.05). Haptoglobin protein expression was also markedly increased in the experimental group compared with in the normal and NC groups (P<0.05). Conversely, there was no significant difference in haptoglobin expression between the NC group and the normal group (P>0.05). The critical value of haptoglobin mRNA in the diagnosis of psoriasis was 2.93, and sensitivity and specificity were 91.3 and 73.6%, respectively. The area under the ROC curve was 0.883 [95% confidence interval (CI)=0.837­0.929]. The critical value of haptoglobin protein in the diagnosis of psoriasis was 0.995, and sensitivity and specificity were 76.1 and 99.9%, respectively. The area under the ROC curve was 0.926 (95% CI=0.837­0.929). The present study demonstrated that the mRNA and protein expression levels of haptoglobin were increased in patients with psoriasis. Haptoglobin mRNA and protein expression were closely associated with the occurrence of psoriasis; therefore, haptoglobin may be considered a promising novel clinical indicator for the diagnosis of psoriasis.

Donor-acceptor-type copolymers based on a naphtho[1,2-c:5,6-c]bis(1,2,5-thiadiazole) scaffold for high-efficiency polymer solar cells.

Four donor-acceptor-type low-bandgap conjugated polymers based on a naphtho[1,2-c:5,6-c]bis(1,2,5-thiadiazole) (NT) acceptor and different donors bridged by a bithiophene spacer have been synthesized through Suzuki or Stille polymerization reactions. Fluorene (F), carbazole (Cz), alkylidene fluorene (AF), and benzodithiophene (BDT) were selected as the donor units to produce a series of new conjugated polymers. Owing to the different electron-donating ability of the donor units, the energy levels, absorption spectra, bandgaps, and carrier mobilities of the resulting polymers were systematically tuned. Bulk-heterojunction-type polymer solar cells based on the new polymers and [6,6]-phenyl-C61 -butyric acid methyl ester (PC61 BM) or [6,6]-phenyl-C71 -butyric acid methyl ester (PC71 BM) were investigated and all of the devices exhibited good photovoltaic performance, with power-conversion efficiencies (PCEs) over 3 %. The best device performance was achieved by PF-C12NT, with an open-circuit voltage (Voc ) of 0.87 V, a short-circuit current density (Jsc ) of 12.19 mA cm(-2) , a fill factor (FF) of 61.36 %, and a PCE of 6.51 % under simulated sunlight (100 mW cm(-2) , AM 1.5G).

Expression of BK-type calcium-activated potassium channel splice variants during chick cochlear development.

The appearance of large-conductance, calcium-activated potassium (BK) current is a hallmark of functional maturation in auditory hair cells. Acquisition of this fast-activating current enables high-frequency, graded receptor potentials in all vertebrates and an electrical tuning mechanism in nonmammals. The gene encoding BK alpha subunits is highly alternatively spliced, and the resulting variations in channel isoforms may contribute to functional diversity at the onset of hearing. We examined the tissue specificity of nine BK alpha alternative exons and investigated changes in expression during chick cochlear development using quantitative polymerase chain reaction (qPCR). Each alternative was widely expressed in several tissues except for an insert near the C-terminus Ca(2+) sensing domain, which appeared brain-specific. The only alternative form in the membrane-bound core of the channel was expressed in brain and muscle but was undetected in cochlea. Of the remaining variants, three increased in expression prior to the onset of hearing and acquisition of BK currents. These three variants cause decreased Ca(2+) sensitivity or increased intracellular retention, traits that would not easily explain the advent of calcium-sensitive currents at embryonic day (E)18-19. Expression levels of other variants were mature and stable by E15, days before currents were acquired. Surface expression of C-terminal isoforms was examined using patch-clamp electrophysiology and immunocytochemistry. C-terminal variants that exhibit robust surface expression appeared in the membrane at E18, even though transcripts were unchanged during development starting from E12. These results indicate that delays in protein synthesis and trafficking/scaffolding of channel subunits underlie the late acquisition of BK currents in cochlear hair cells.

Developmental expression of BK channels in chick cochlear hair cells.

BACKGROUND: Cochlear hair cells are high-frequency sensory receptors. At the onset of hearing, hair cells acquire fast, calcium-activated potassium (BK) currents, turning immature spiking cells into functional receptors. In non-mammalian vertebrates, the number and kinetics of BK channels are varied systematically along the frequency-axis of the cochlea giving rise to an intrinsic electrical tuning mechanism. The processes that control the appearance and heterogeneity of hair cell BK currents remain unclear. RESULTS: Quantitative PCR results showed a non-monotonic increase in BK alpha subunit expression throughout embryonic development of the chick auditory organ (i.e. basilar papilla). Expression peaked near embryonic day (E) 19 with six times the transcript level of E11 sensory epithelia. The steady increase in gene expression from E11 to E19 could not explain the sudden acquisition of currents at E18-19, implicating post-transcriptional mechanisms. Protein expression also preceded function but progressed in a sequence from diffuse cytoplasmic staining at early ages to punctate membrane-bound clusters at E18. Electrophysiology data confirmed a continued refinement of BK trafficking from E18 to E20, indicating a translocation of BK clusters from supranuclear to subnuclear domains over this critical developmental age. CONCLUSIONS: Gene products encoding BK alpha subunits are detected up to 8 days before the acquisition of anti-BK clusters and functional BK currents. Therefore, post-transcriptional mechanisms seem to play a key role in the delayed emergence of calcium-sensitive currents. We suggest that regulation of translation and trafficking of functional alpha subunits, near voltage-gated calcium channels, leads to functional BK currents at the onset of hearing.