Mapping the developmental potential of mouse inner ear organoids at single-cell resolution.

Inner ear organoids recapitulate development and are intended to generate cell types of the otic lineage for applications such as basic science research and cell replacement strategies. Here, we use single-cell sequencing to study the cellular heterogeneity of late-stage mouse inner ear organoid sensory epithelia, which we validated by comparison with datasets of the mouse cochlea and vestibular epithelia. We resolved supporting cell sub-types, cochlear-like hair cells, and vestibular type I and type II-like hair cells. While cochlear-like hair cells aligned best with an outer hair cell trajectory, vestibular-like hair cells followed developmental trajectories similar to in vivo programs branching into type II and then type I extrastriolar hair cells. These results highlight the transcriptional accuracy of the organoid developmental program but will also inform future strategies to improve synaptic connectivity and regional specification.

Enhancing humification and microbial interactions during co-composting of pig manure and wine grape pomace: The role of biochar and Fe2O3.

Phenol-rich wine grape pomace (WGP) improves the conversion of pig manure (PM) into humic acid (HA) during composting. However, the impact of using combinations of Fe2O3 and biochar known to promote compost maturation remains uncertain. This research explored the individual and combined influence of biochar and Fe2O3 during the co-composting of PM and WGP. The findings revealed that Fe2O3 boosts microbial network symbiosis (3233 links), augments the HA yield to 3.38 by promoting polysaccharide C-O stretching, and improves the germination index to 124.82 %. Limited microbial interactions, increased by biochar, resulted in a lower HA yield (2.50). However, the combination weakened the stretching of aromatics and quinones, which contribute to the formation of HA, resulting in reduced the humification to 2.73. In addition, Bacillus and Actinomadura were identified as pivotal factors affecting HA content. This study highlights Fe2O3 and biochar's roles in phenol-rich compost humification, but combined use reduces efficacy.

Structural optimization of BODIPY photosensitizers for enhanced photodynamic antibacterial activities.

Enhancing the interactions between photosensitizers and bacteria is key to developing effective photodynamic antibacterial agents. However, the influence of different structures on the therapeutic effects has not been systematically investigated. Herein, 4 BODIPYs with distinct functional groups, including the phenylboronic acid (PBA) group and pyridine (Py) cations, were designed to explore their photodynamic antibacterial activities. The BODIPY with the PBA group (IBDPPe-PBA) exhibits potent activity against planktonic Staphylococcus aureus (S. aureus) upon illumination, while the BODIPY with Py cations (IBDPPy-Ph) or both the PBA group and Py cations (IBDPPy-PBA) can significantly minimize the growth of both S. aureus and Escherichia coli (E. coli). In particular, IBDPPy-Ph can not only eliminate the mature S. aureus biofilm and E. coli biofilm in vitro, but also promote the healing of the infected wound. Our work provides an alternative for reasonable design of photodynamic antibacterial materials.

Structural Engineering of Ionic MOF@COF Heterointerface for Exciton-Boosting Sunlight-Driven Photocatalytic Filter.

Sunlight-driven photocatalytic filters against pathogenic bioaerosols have attracted a lot of interest. However, developing an efficient interception system that shows enhanced visible-light harvesting, controllable charge dynamic, and boosted ROS generation remains a grand challenge. Here, we designed an ionic ZIF-8@iCOF nanocomposite as a sunlight-driven photocatalytic filter through elaborate structural engineering of the heterointerface between ZIF-8 and cationic iCOF layers. The photoactive experiments reveal significant improvements in the visible light absorption and sunlight-driven exciton-enhanced intersystem crossing to boost the generation of singlet oxygen (220%) and also obtain antibacterial efficiency of 99.99999% after 15 min irradiation. After combining with commercial polymer, resultant ZIF-8@iCOF/polyacrylonitrile (PAN) fibrous membranes exhibited high interception efficiency for both PM10 and PM2.5 (98%), being close to the commercial N95. This fibrous membrane also possesses good biocompatibility and strong elimination of bacteria under sunlight conditions, satisfying for the long-lasting contact usage. This finding not only showcases the promise of the porous materials-based fibrous membranes for efficient photocatalytic filter against pathogenic bioaerosols but also highlights the importance of accurate structural engineering for the advancement of sunlight-driven photocatalytic systems in environment and energy-related fields.

Different Stepwise Growth Mechanism of AIE-Active Tetraphenylethylene-Functionalized Metal-Organic Frameworks on Au(111) and Cu(111) Surfaces.

Fabricating tetraphenylethylene (TPE)-functionalized metal-organic frameworks (MOFs) with aggregation- induced emission on surfaces and understanding the growth mechanism have not yet been pursued. Herein, MOFs constructed via the Ullmann-type reaction of a C2-symmetry TPE derivative (p-BrTBE) on Au(111) and Cu(111) surfaces were thoroughly investigated using scanning tunneling microscopy. On a Au(111) surface, p-BrTBE molecules formed the self-assembled pattern at 298 K. Stepwise annealing led to a progressive evolution process, in which the stepwise debromination reaction led to organometallic intermediates, and surface-stabilized radicals and metal-organic networks were formed. By contrast, the relatively ordered MOFs were obtained by replacing the underlying substrate with the more catalytically active Cu(111) at 298 K. Density functional theory calculations demonstrated that the formation of different networks on Au(111) and Cu(111) was determined by the different conformations of the TBE unit on the different substrates due to the different adsorption energy.

Effect of biochar addition on copper and zinc passivation pathways mediated by humification and microbial community evolution during pig manure composting.

The mobility and bioavailability of Cu and Zn are the main threats associated with the land application of pig manure (PM) compost products. This study investigated the impacts of biochar (BC) concentration on passivation of Cu and Zn associated with the compost maturity. The results indicated that 15% and 10% BC favoured the passivation of Cu and Zn, respectively. BC promoted passivation of Cu by accelerating HA production and optimized the abundance of Firmicutes. BC promoted the passivation of Zn by increasing the high temperature peak and the corresponding pH (8-8.5). A higher level (15% and 20%) of BC altered the dominant bacterial phylum from Firmicutes to Proteobacteria. 20% BC inhibited the passivation of Cu and Zn by reducing the highest temperature and lowering the alkalinity of substrate. These results offer new insights into understanding how the addition of BC could reduce the risk of hazardous products during PM composting.

Multivariate Strategy Preparation of Nanoscale Ru-Doped Metal-Organic Frameworks with Boosted Photoactivity for Bioimaging and Reactive Oxygen Species Generation.

How to incorporate chromophores into MOFs is a key for the development of multifunctional photoactive systems. The poor internalization by cancer cells and low efficiency of ROS generation hamper the potential clinic application of Ru-based molecular agents. In this work, a nanoscale Ru-doped metal-organic framework Hf-UiO-Ru (Hf-Ru) with framework-boosted photoactivities was prepared via a multivariate strategy for use in bioimaging and ROS generation. The as-synthesized Hf-Ru nanocrystals not only maintain the well regular morphology and crystal structure in comparison with that of the Hf-UiO-66 prototype but also give an oxygen-independent emission with a much longer lifetime, higher quantum yield, and stronger ROS generation than molecular Ru(dcbpy)3. Additionally, the enhanced cellular uptake and high brightness in fluorescence and CT imaging of Hf-Ru nanocrystals have also been well studied in vitro. This multivariate strategy may be utilized as a general paradigm to develop a photoactive nanosystem for bioimaging and cancer treatment.

Stepwise on-surface synthesis of thiophene-based polymeric ribbons by coupling reactions and the carbon-fluorine bond cleavage.

The rational synthesis of thiophene-based cross-coupled polymers on surfaces has been attracting more attention recently. Here, we report the stepwise activation of 5,5'-(2,3-difluoro-1,4-phenylene)bis(2-bromothiophene) as a precursor to synthesize thiophene-based polymeric ribbons on the Au(111) surface. Scanning tunneling microscopy studies showed that the precursor adopted different conformations in the self-assembled structure, organometallic species, and covalent polymers. On annealing the sample at a relatively low temperature (150 °C), the conversion of the organometallic structure into a covalent product with straight lines was observed, in which the Br adatoms arranged between the neighboring chains. On further annealing the sample at 270 °C, the detached Br adatoms played a key role in promoting the C-H bond activation. The cross-linked polymer was achieved by a combination of Ullmann and dehydrogenative coupling. When the annealing temperature was up to 390 °C, the C-F bond activation was triggered, which led to the formation of polymeric ribbons resulting from the cyclodehydrogenation of the fluorinated polymer. This study further supplements the reaction mechanism of thiophene-based dehalogenative, dehydrogenative and defluorinative coupling, and provides us a rational way for synthesizing cross-linked functional materials.

Matrigel is required for efficient differentiation of isolated, stem cell-derived otic vesicles into inner ear organoids.

Inner ear organoids derived from pluripotent stem cells could be a useful model system to study development, disease, and regeneration. However, there is considerable heterogeneity in the size, morphology, and efficiency of organoid production using standard protocols. Greater control of the culture microenvironment could decrease heterogeneity and increase the yield of organoids. Animal-derived otic vesicles show some autonomy during development and can differentiate into cochlear and vestibular domains in mesenchyme-free ex vivo culture. Therefore, we investigated whether stem cell-derived otic vesicles can autonomously generate inner ear organoids. Isolated, stem cell-derived vesicles grew into cyst-like organoids with high efficiency, over 90%, when embedded in droplets of the basement membrane matrix Matrigel. Though nearly all vesicles within the aggregate were competent to mature into organoids, the efficiency of organoid production depended on the stage of vesicle isolation and required supplementation with Matrigel.

Conformation modification of terthiophene during the on-surface synthesis of pure polythiophene.

On-surface coupling under ultra-high vacuum is employed as a versatile approach to synthesize pure polythiophene from a 5,5''-dibromo-2,2':5',2''-terthiophene (DBTT) precursor and the corresponding temperature-dependent stepwise reaction mechanism is systematically studied by scanning tunneling microscopy (STM). After thermal deposition of the precursor onto a Au(111) surface that is kept at room temperature, a triangle-like pattern and a linear self-assembled pattern are formed with different molecular coverages through BrBrS halogen bonds and BrBr type-I contact bonds, respectively. In the self-assembled nanostructures, the thiophene units adopt trans-conformation. Mild annealing promotes the structural transition of both nanostructures into ordered zigzag organometallic linear chains with all-cis configured thiophene units connected through coordination bonds to the Au adatoms. Such conformational variety is easily recognized by STM, particularly in the case of DBTT-CH3 with the extra -CH3 signals. The covalently coupled products from the DBTT precursor are obtained by further annealing the organometallic intermediate at higher temperatures, which leads to the removal of Au atoms and the formation of ordered polymer chains and disordered polythiophene networks. Further characterization suggests that the reaction mechanism is associated with Ullmann-type coupling to form the ordered chains as well as Ullmann-type and dehydrogenative C-C coupling to fabricate cross-linked polymer networks. Compared with the on-surface synthesis process of DBTT on the Cu(111) surface, it can be confirmed that the Au adatoms are vital to synthesize polythiophene. These findings provide important insight into the reaction mechanism of on-surface synthesized pure polythiophene and on-surface coupling can potentially be applied to synthesize other functional conjugated polymers.

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.

A Wide-Bandgap Conjugated Polymer Based on Quinoxalino[6,5-f ]quinoxaline for Fullerene and Non-Fullerene Polymer Solar Cells.

A wide-bandgap conjugated polymer, PNQx-2F2T, based on a ring-fused unit of quinoxalino[6,5-f ]quinoxaline (NQx), is synthesized for use as electron donor in polymer solar cells (PSCs). The polymer shows intense light absorption in the range from 300 to 740 nm and favorable energy levels of frontier molecular orbitals. The polymer has afforded decent device performance when blended with either fullerene-based acceptor [6,6]-phenyl-C71 -butylric acid methyl ester ([70]PCBM) or non-fullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone-methyl))-5,5,11,11-tetrakis(4-n-hexylphenyl)-dithieno[2,3-d: 2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-M). The highest PCEs of 7.9% and 7.5% have been achieved for [70]PCBM or IT-M based PSCs, respectively. Moreover, the influence of molecular weight of PNQx-2F2T on solar cell performance has been investigated. It is found that fullerene-based devices prefer higher polymer molecular weight, while non-fullerene devices are not susceptible to the molecular weight of PNQx-2F2T. The device results are extensively explained by electrical and morphological characterizations. This work not only evidences the potential of NQx for constructing high-performance photovoltaic polymers but also demonstrates a useful structure-performance relationship for efficiency enhancement of non-fullerene PSCs via the development of new conjugated polymers.

MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1.

BACKGROUND/AIMS: Melanoma is one of the most aggressive malignant tumors, with increasing incidence, poor prognosis, and lack of any effective targeted therapies. Abnormal expression of miR-29a has been found in several types of cancers, including melanoma. In this study, experiments were performed to investigate the role of miR-29a in melanoma, and the molecular mechanism by which miR-29a represses melanoma. METHODS: miR-29 and Bmi1 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability, apoptosis, migration and invasion were respectively determined by Cell Counting Kit-8 assay, Propidium iodide (PI) fluorescein isothiocynate (FITC)-Annexin V staining assay, wound healing assay and transwell assay. Luciferase reporter assay was performed to determine a target gene of miR-29a. Western blot was used to analyze protein expression of apoptosis-related proteins, Bmi1, Wnt/ß-catenin and Nuclear factor-κB (NF-κB) pathway target genes. RESULTS: miR-29a was down-regulated in all tested melanoma cell lines. Up-regulation of miR-29a effectively inhibited cell viability, migration, and invasion, but promoted apoptosis in A375 cells. Bmi1 was a direct target gene of miR-29a. Transfection with miR-29a mimic decreased cell migration and invasion and Bmi1 expression in Malme-3M cells, SK-MEL-2, SK-MEL-5, and M14 cell lines. Moreover, miR-29a might suppress growth, migration and invasion of A375 cells by negatively regulating Bmi1. In addition, our results demonstrated that transfection with miR-29a mimic effectively blocked Wnt/ß-catenin and NF-κB pathways via down-regulating Bmi1. CONCLUSION: miR-29a could be functioned as a potential tumor suppressor through direct regulation of Bmi1 in melanoma cells.

High-Performance Ternary Nonfullerene Polymer Solar Cells with Both Improved Photon Harvesting and Device Stability.

Efficiency and stability of polymer solar cells (PSCs) are the two most significant decisive factors for the purpose of actual applications. Here, highly efficient and stable ternary PSCs were fabricated by incorporating two well-compatible polymer donors (poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2- b;4,5- b0]dithiophene-2,6-diyl- alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4- b]thiophene-)-2-carboxylate-2-6-diyl] and poly[[9-(1-octylnonyl)-9 H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl]) with one narrow band gap nonfullerene acceptor (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3- d:2',3'- d']- s-indaceno[1,2- b:5,6- b']dithiophene)). It is found that Förster resonance energy transfer acts as an efficient pathway to further strengthen photon harvesting in this ternary system, which results in a significant improvement in current density ( JSC) without sacrificing the strong absorption of binary blends in the near-infrared region. Meanwhile, both of the inverted and conventional ternary PSCs exhibit better stability compared with the related binary PSCs in air condition because of the interlocked morphology in ternary films. The optimized ternary PSCs exhibit an outstanding power conversion efficiency (PCE) of 9.53% resulting from the synchronous improvements in JSC and fill factor. Moreover, this ternary strategy can be further confirmed by the use of an ultranarrow-band gap nonfullerene acceptor IEICO-4F, and the champion PCE of ternary PSCs reaches to 12.15%.

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.

WITHDRAWN: MiR-29a Inhibits Growth and Metastasis of Melanoma A375 Cells by Directly Targeting Bmi1.

Ahead of Print article withdrawn by publisher

Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

Impairment of spiral ganglion neurons (SGNs) of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM), the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC) were differentiated into neural precursor cells (NPCs) and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus). To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

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.

microRNA-130a Promotes Human Keratinocyte Viability and Migration and Inhibits Apoptosis Through Direct Regulation of STK40-Mediated NF-κB Pathway and Indirect Regulation of SOX9-Meditated JNK/MAPK Pathway: A Potential Role in Psoriasis.

Psoriasis is a chronic inflammatory skin disorder. The aim of this study was to determine a potential role of microRNA (miR)-130a in psoriasis, and underlying mechanism. Expression levels of miR-130a in psoriasis specimens and normal skin tissues were analyzed. MiR-130a mimic, inhibitor, miR-control, small interfering RNA (siRNA) specific serine/threonine kinase 40 (STK40), or sex-determining region Y chromosome-box 9 (SOX9) were transfected to human keratinocyte HaCaT cells, respectively. After transfection, the cell viability, apoptosis, and migration were determined. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction, and western blot were performed to explore whether STK40 was a target of miR-130a. The effects of aberrant expressions of miR-130a, STK40, or SOX9 on key proteins of NF-κB and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway were assessed. The miR-130a levels were significantly higher in patients with psoriasis compared to the healthy controls (p < 0.01). Overexpressing miR-130a strikingly promoted HaCaT cell viability and migration and inhibited apoptosis (p < 0.01 or p < 0.05). We confirmed that STK40 was a direct target of miR-130a, and STK40 was involved in miR-130a-induced cell functions. Overexpressing miR-130a significantly upregulated NF-κB p65, SOX9, p-c-Jun, p-JNK, and p-p38MAPK proteins and silencing miR-130a downregulated them. In addition, silencing STK40 alleviated the effects of anti-miR-130a on SOX9 expression. Furthermore, silencing SOX9 also decreased levels of p-c-Jun, p-JNK, and p-p38MAPK proteins. MiR-130a regulates human keratinocyte HaCaT viability, migration and apoptosis might be by direct regulation of STK40-mediated NF-κB pathway and by indirect regulation of SOX9-mediated downstream JNK/MAPK signaling pathway.

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.