Occupational noise and hypertension in Southern Chinese workers: a large occupational population-based study.

INTRODUCTION: An increasing number of original studies suggested that occupational noise exposure might be associated with the risk of hypertension, but the results remain inconsistent and inconclusive. In addition, the attributable fraction (AF) of occupational noise exposure has not been well quantified. We aimed to conduct a large-scale occupational population-based study to comprehensively investigate the relationship between occupational noise exposure and blood pressure and different hypertension subtypes and to estimate the AF for hypertension burden attributable to occupational noise exposure. METHODS: A total of 715,135 workers aged 18-60 years were included in this study based on the Key Occupational Diseases Surveillance Project of Guangdong in 2020. Multiple linear regression was performed to explore the relationships of occupational noise exposure status, the combination of occupational noise exposure and binaural high frequency threshold on average (BHFTA) with systolic and diastolic blood pressure (SBP, DBP). Multivariable logistic regression was used to examine the relationshipassociation between occupational noise exposure status, occupational noise exposure combined with BHFTA and hypertension. Furthermore, the attributable risk (AR) was calculated to estimate the hypertension burden attributed to occupational exposure to noise. RESULTS: The prevalence of hypertension among occupational noise-exposed participants was 13·7%. SBP and DBP were both significantly associated with the occupational noise exposure status and classification of occupational noise exposure combined with BHFTA in the crude and adjusted models (all P < 0·0001). Compared with workers without occupational noise exposure, the risk of hypertension was 50% greater among those exposed to occupational noise in the adjusted model (95% CI 1·42-1·58). For participants of occupational noise exposed with BHFTA normal, and occupational noise exposed with BHFTA elevated, the corresponding risks of hypertension were 48% (1·41-1·56) and 56% (1·46-1·63) greater than those of occupational noise non-exposed with BHFTA normal, respectively. A similar association was found in isolated systolic hypertension (ISH) and prehypertension. Subgroup analysis by sex and age showed that the positive associations between occupational noise exposure and hypertension remained statistically significant across all subgroups (all P < 0.001). Significant interactions between occupational noise status, classification of occupational noise exposure combined with BHFTA, and age in relation to hypertension risk were identified (all P for interaction < 0.001). The associations of occupational noise status, classification of occupational noise exposure combined with BHFTA and hypertension were most pronounced in the 18-29 age groups. The AR% of occupational noise exposure for hypertension was 28·05% in the final adjusted model. CONCLUSIONS: Occupational noise exposure was positively associated with blood pressure levels and the prevalence of hypertension, ISH, and prehypertension in a large occupational population-based study. A significantly increased risk of hypertension was found even in individuals with normal BHFTA exposed to occupational noise, with a further elevated risk observed in those with elevated BHFTA. Our findings provide epidemiological evidence for key groups associated with occupational noise exposure and hypertension, and more than one-fourth of hypertension cases would have been prevented by avoiding occupational noise exposure.

Circ-EGFR Functions as an Inhibitory Factor in the Malignant Progression of Glioma by Regulating the miR-183-5p/TUSC2 Axis.

Circular RNAs (circRNAs) have pivotal functions in regulating diverse biological processes of human tumors, including glioma. Herein, a novel circRNA epidermal growth factor receptor (circ-EGFR, hsa_circ_0080223) was researched in glioma. The molecular expression levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to assess cell proliferation. Apoptosis was analyzed using flow cytometry. Cell migration and invasion were examined via transwell assay. Interaction relations between targets were verified using dual-luciferase reporter assay. Tumor Suppressor Candidate 2 (TUSC2) protein expression was examined by Western blot. In vivo experiment was performed by establishing xenograft model in mice. The qRT-PCR showed the downregulation of circ-EGFR and TUSC2 but the upregulation of microRNA-183-5p (miR-183-5p) in glioma samples. In vitro assays revealed that circ-EGFR overexpression induced the repression of cell proliferation, migration, and invasion but the promotion of apoptosis. Circ-EGFR was identified as a sponge of miR-183-5p and circ-EGFR-mediated glioma progression inhibition was abolished by miR-183-5p downregulation. Additionally, miR-183-5p targeted TUSC2 and miR-183-5p inhibitor impeded the development of glioma by upregulating the expression of TUSC2. Furthermore, circ-EGFR could regulate the TUSC2 level by sponging miR-183-5p. Glioma growth in vivo was also reduced by circ-EGFR via targeting the miR-183-5p/TUSC2 axis. Altogether, our results suggested that circ-EGFR inhibited the malignant progression of glioma by regulating the levels of miR-183-5p and TUSC2. Circ-EGFR may be a useful therapeutic target to antagonize the glioma progression.

Neuroprotective effect of aldose reductase knockout in a mouse model of spinal cord injury involves NF-κB pathway.

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. Aldose reductase (AR) has recently been shown to be a key component of the innate immune response. However, the mechanisms involved in AR and innate immune response remain unclear. In this study, wild-type (WT) or AR-deficiency (KO) mice were subjected to SCI by a spinal crush injury model. AR KO mice showed better locomotor recovery and smaller injury lesion areas after spinal cord crushing compared with WT mice. Here, we first demonstrated that AR deficiency repressed the expression level of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in vitro via the activation of autophagy. AR deficiency caused 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation in LPS-induced macrophages. We also found that exogenous addition of low concentrations of 4-HNE in LPS-induced macrophages had the effect of promoting further activation of NF-κB pathway, whereas high concentrations of 4-HNE had inhibitory effects. Together, these results indicated that autophagy as a mechanism underlying AR and 4-HNE in LPS-induced macrophages.

Compact quasi-optical mode converter based on anisotropic metasurfaces.

In this paper, a novel compact quasi-optical mode converter based on anisotropic metasurfaces for high-order mode terahertz electronic devices is presented. To demonstrate the design model, a Ka-band metasurface quasi-optical mode converter that converts cylindrical waveguide TE01 mode to circularly polarized Gaussian beam is designed and fabricated. Both electromagnetic simulation and experiment results show that the Gaussian beam can be observed from 35 to 38 GHz, corresponding to over 8.5% of the bandwidth. The maximum scalar Gaussian mode content of 97.85% is observed in the experiment, and the output radiation from the metasurface quasi-optical mode converter is approximate circular polarization. This work unveils the potential of compact quasi-optical mode converter based on metasurfaces.

Dirac Spin Liquid on the Spin-1/2 Triangular Heisenberg Antiferromagnet.

We study the spin liquid candidate of the spin-1/2 J_{1}-J_{2} Heisenberg antiferromagnet on the triangular lattice by means of density matrix renormalization group (DMRG) simulations. By applying an external Aharonov-Bohm flux insertion in an infinitely long cylinder, we find unambiguous evidence for gapless U(1) Dirac spin liquid behavior. The flux insertion overcomes the finite size restriction for energy gaps and clearly shows gapless behavior at the expected wave vectors. Using the DMRG transfer matrix, the low-lying excitation spectrum can be extracted, which shows characteristic Dirac cone structures of both spinon-bilinear and monopole excitations. Finally, we confirm that the entanglement entropy follows the predicted universal response under the flux insertion.

Identification of miRNA-7 by genome-wide analysis as a critical sensitizer for TRAIL-induced apoptosis in glioblastoma cells.

Glioblastoma (GBM) is still one of the most lethal forms of brain tumor despite of the improvements in treatments. TRAIL (TNF-related apoptosis-inducing ligand) is a promising anticancer agent that can be potentially used as an alternative or complementary therapy because of its specific antitumor activity. To define the novel pathways that regulate susceptibility to TRAIL in GBM cells, we performed a genome-wide expression profiling of microRNAs in GBM cell lines with the distinct sensitivity to TRAIL-induced apoptosis. We found that the expression pattern of miR-7 is closely correlated with sensitivity of GBM cells to TRAIL. Furthermore, our gain and loss of function experiments showed that miR-7 is a potential sensitizer for TRAIL-induced apoptosis in GBM cells. In the mechanistic study, we identified XIAP is a direct downstream gene of miR-7. Additionally, this regulatory axis could also exert in other types of tumor cells like hepatocellular carcinoma cells. More importantly, in the xenograft model, enforced expression of miR-7 in TRAIL-overexpressed mesenchymal stem cells increased apoptosis and suppressed tumor growth in an exosome dependent manner. In conclusion, we identify that miR-7 is a critical sensitizer for TRAIL-induced apoptosis, thus making it as a promising therapeutic candidate for TRAIL resistance in GBM cells.

Quantum Domain Walls Induce Incommensurate Supersolid Phase on the Anisotropic Triangular Lattice.

We investigate the extended hard-core Bose-Hubbard model on the triangular lattice as a function of spatial anisotropy with respect to both hopping and nearest-neighbor interaction strength. At half-filling the system can be tuned from decoupled one-dimensional chains to a two-dimensional solid phase with alternating density order by adjusting the anisotropic coupling. At intermediate anisotropy, however, frustration effects dominate and an incommensurate supersolid phase emerges, which is characterized by incommensurate density order as well as an anisotropic superfluid density. We demonstrate that this intermediate phase results from the proliferation of topological defects in the form of quantum bosonic domain walls. Accordingly, the structure factor has peaks at wave vectors, which are linearly related to the number of domain walls in a finite system in agreement with extensive quantum Monte Carlo simulations. We discuss possible connections with the supersolid behavior in the high-temperature superconducting striped phase.

Endoscopic submucosal dissection versus transanal local excision for rectal carcinoid: a comparative study.

AIM: The aim of this study is to compare the short-term clinical outcomes between endoscopic submucosal dissection and transanal local excision for rectal carcinoid tumors. METHODS: Between 2007 and 2012, 31 patients with rectal carcinoid underwent endoscopic submucosal dissection at our hospital. They were compared with a matched cohort of 23 patients who underwent transanal local excision for rectal carcinoid between 2007 and 2012. Short-term clinical outcomes including surgical parameters, postoperative recovery, and oncologic outcomes were compared between the two groups. RESULTS: The mean size of tumors was significantly bigger in the transanal local excision group (0.8 ± 0.2 versus 1.1 ± 0.5 cm; P = 0.018). En bloc resection was achieved for 30 patients (97 %) in the endoscopic submucosal dissection group and all the patients in the transanal local excision group. The operation time was longer in the transanal local excision than that in the endoscopic submucosal dissection group (40.0 ± 22.7 min versus 12.2 ± 5.3 min; P < 0.001). Complications in the transanal local excision group were five cases of acute retention of urine. There was no local recurrence or distant metastasis in either group during the follow-up period. CONCLUSION: For the treatment of rectal carcinoid tumors with diameter <1 cm, endoscopic submucosal dissection has better short-term clinical outcomes than transanal local excision in terms of faster recovery and possibly a lower morbidity rate. Transanal local excision may be the first therapeutic choice of scar-embedded rectal carcinoid tumors.

Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane.

1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn(2+))-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p<0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn(2+)-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

Symmetry-Protected Topological Phase in a One-Dimensional Correlated Bosonic Model with a Synthetic Spin-Orbit Coupling.

By performing large-scale density-matrix renormalization group simulations, we investigate a one-dimensional correlated bosonic lattice model with a synthetic spin-orbit coupling realized in recent experiments. In the insulating regime, this model exhibits a symmetry-protected topological phase. This symmetry-protected topological phase is stabilized by time-reversal symmetry and it is identified as a Haldane phase. We confirm our conclusions further by analyzing the entanglement spectrum. In addition, we find four conventional phases: a Mott insulating phase with no long range order, a ferromagnetic superfluid phase, a ferromagnetic insulating phase, and a density-wave phase.

MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells.

Growing evidence has demonstrated that the aberrant expression of miRNA is a hallmark of malignancies, indicating the important roles of miRNA in the development and progression of cancer. MiR-7 is considered as a tumor suppressor miRNA in multiple types of cancer. However, the role of miR-7 in human hepatocellular carcinoma (HCC) and its underlying mechanism remain elusive. In this study, we found that overexpression of miR-7 arrested cell cycle at G1 to S transition in HCC. By combinational use of bioinformatic prediction, reporter assay, quantitative real-time PCR (qRT-PCR) and Western blot, we confirmed that CCNE1, an important mediator in G1/S transition is one of new direct target genes of miR-7. Further studies revealed that silencing of CCNE1 recapitulated the effects of miR-7 overexpression, whereas enforced expression of CCNE1 reversed the suppressive effects of miR-7 in cell cycle regulation. Finally, analysis of qRT-PCR showed a reciprocal relationship between miR-7 and CCNE1 in clinical cancer tissues and multiple types of tumor cell lines. These findings indicate that miR-7 exerts tumor-suppressive effects in hepatocarcinogenesis through the suppression of oncogene CCNE1 expression and suggest a therapeutic application of miR-7 in HCC.

Berry-phase-induced dimerization in one-dimensional quadrupolar systems.

We investigate the effect of the Berry phase on quadrupoles that occur, for example, in the low-energy description of spin models. Specifically, we study here the one-dimensional bilinear-biquadratic spin-one model. An open question for many years about this model is whether it has a nondimerized fluctuating nematic phase. The dimerization has recently been proposed to be related to Berry phases of the quantum fluctuations. We use an effective low-energy description to calculate the scaling of the dimerization according to this theory and then verify the predictions using large scale density-matrix renormalization group simulations, giving good evidence that the state is dimerized all the way up to its transition into the ferromagnetic phase. We furthermore discuss the multiplet structure found in the entanglement spectrum of the ground state wave functions.

A description of the hepatitis B virus genomic background in a high-prevalence area in China.

BACKGROUND: Hepatitis B (HB) is an important disease worldwide. Almost 350 million people are positive for Hepatitis B virus surface antigen (HBsAg), and one-third of them live in China. According to a nation-wide serosurvey in China in 2006, the prevalence of HBsAg was higher in Northwest China than in other areas. However, the epidemic HBV strains in this area are poorly studied. RESULTS: In this study, 242 complete hepatitis B virus (HBV) genome sequences were obtained from HBV asymptomatic carriers in major cities of Northwest China. The 242 HBV sequences clustered into genotypes B, C and D. Through comparison of the genotype consensus sequences, 158 genotype-dependent positions were observed in P, S and X ORFs. Clinically relevant mutation screening in this study revealed that no HBV antiviral drug resistance mutations were observed and the vaccination failure mutations were heavily underrepresented. CONCLUSIONS: The role of genotype D strains in HBV prevalence should not be ignored in Northwest China. Due to low prevalence of vaccination failure mutations, it can be inferred that the genotype B, C and D strains in Northwest China may have less likelihood of vaccine escape.

The relative contribution of PM2.5 components to the obstructive ventilatory dysfunction-insights from a large ventilatory function examination of 305,022 workers in southern China.

BACKGROUND: The new round of WHO/ILO Joint Estimates of the Work-related Burden of Disease assessment requires futher research to provide more evidence, especially on the health impact of ambient air pollution around the workplace. However, the evidence linking obstructive ventilatory dysfunction (OVD) to fine particulate matter (PM2.5) and its chemical components in workers is very limited. Evidence is even more scarce on the interactive effects between occupational factors and particle exposures. We aimed to fill these gaps based on a large ventilatory function examination of workers in southern China. METHODS: We conducted a cross-sectional study among 363,788 workers in southern China in 2020. The annual average concentration of PM2.5 and its components were evaluated around the workplace through validated spatiotemporal models. We used mixed-effect models to evaluate the risk of OVD related to PM2.5 and its components. Results were further stratified by basic characteristics and occupational factors. FINDINGS: Among the 305,022 workers, 119,936 were observed with OVD. We found for each interquartile range (IQR) increase in PM2.5 concentration, the risk of OVD increased by 27.8 (95 % confidence interval (CI): 26.5-29.2 %). The estimates were 10.9 % (95 %CI: 9.7-12.1 %), 15.8 % (95 %CI: 14.5-17.2 %), 2.6 % (95 %CI: 1.4-3.8 %), 17.1 % (95 %CI: 15.9-18.4 %), and 11 % (95 %CI: 9.9-12.2 %), respectively, for each IQR increment in sulfate, nitrate, ammonium salt, organic matter and black carbon. We observed greater effect estimates among females, younger workers, workers with a length of service of 24-45 months, and professional skill workers. Furthermore, it is particularly noteworthy that the noise-exposed workers, high-temperature-exposed workers, and less-dust-exposed workers were at a 5.7-68.2 % greater risk than others. INTERPRETATION: PM2.5 and its components were significantly associated with an increased risk of OVD, with stronger links among certain vulnerable subgroups.

Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation.

Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of the G-protein-coupled receptor (APJ), is abundantly expressed in diverse organs. The apelin-APJ axis helps to control pathological and physiological processes in lung. The role of apelin in the pathological process and its possible therapeutic effects on silicosis have not been elucidated. In this study, we found that lung expression and circulating levels of apelin were markedly decreased in silicosis patients and silica-induced fibrotic mice and associated with the severity. Furthermore, in vivo data demonstrated that pre-treatment from day 3 and post-treatment from day 15 with apelin could both alleviate silica-induced pulmonary fibrosis in mice. Besides, apelin inhibited pulmonary fibroblast activation via transforming growth factor beta 1 (TGF-ß1) signaling. Our study suggested that apelin could prevent and reverse silica-induced pulmonary fibrosis by inhibiting the fibroblast activation through TGF-ß1 signaling pathway, thus providing a new potential therapeutic strategy for silicosis and other pulmonary fibrosis.

Rapid Evaporation of a Metal Electrode for a High-Efficiency Perovskite Solar Cell.

Organic-inorganic hybrid perovskite solar cells (PSCs) have attracted considerable attention due to the excellent optoelectronic properties of perovskite materials. The energy consumption and high cost issues of metal electrode evaporation should be addressed before large-scale manufacturing and application. We developed an effective metal electrode evaporation procedure for the fabrication of high-efficiency planar heterojunction (PHJ) PSCs, with an inverted device structure of glass/indium tin oxide (ITO)/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA)/perovskite/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM)/(E)-ß-caryophyllene (BCP)/Ag. The effect of the evaporation rate for an evaporator with a small-volume metal cavity on the performance of PHJ-PSC devices was investigated systematically. Through controlling the processes of Ag electrode evaporation, the charge dynamics of the devices were studied by analyzing their charge recombination resistance and lifetime, as well as their defect state density. Our findings reveal that the evaporation rate of an evaporator with a small cavity is favorable for the performance of PHJ-PSCs. As a result, PHJ-PSCs fabricated using a very thin, non-doped PTAA film exhibit photoelectric conversion efficiency (PCE) of 19.21%, with an open-circuit voltage (Voc) of 1.132 V. This work showcases the great potential of rapidly evaporating metal electrodes to reduce fabrication costs, which can help to improve the competitiveness in the process of industrialization.

Application of grading evaluation method of water radioactivity level in Chongqing section of Yangtze River.

The major rivers in a region are usually vital sources of drinking water for local populations, and the concentration of radionuclides in the water is intimately tied to people's health. The varying concentration limits set by the World Health Organization are appropriate as screening values for determining the pollution of water sources, but their capacities as regulatory or early warning limits are restricted. In daily management, the regulatory authority needs to manage water bodies by level based on the concentration of radionuclide to indicate the potential pollution risks. From 2017 to 2019, a statistical analysis and dosage evaluation were conducted on the water radioactivity level in the Chongqing section of the Yangtze River in this study. The Modified Nemerow Index method based on the dose conversion coefficients was applied for the grading evaluation of the water radioactivity level, allowing the grading effect discussed. The results showed that the concentration of radionuclides in the Chongqing section of the Yangtze River and its contribution to the annual effective dose of the human body were lower than the limits stated in the Guidelines for Drinking Water Quality (Fourth Edition). And the samples in the section were 52.94% in Grade Ⅰand 47.06% in Grade Ⅱ, meaning few potential radioactive pollution risks exist there. Compared with other methods. The Modified Nemerow Index method combines the Traditional Nemerow Index method with the dose conversion coefficient of nuclides making it more realistic for the early warning and control of radioactive pollution in water bodies, which is worth popularizing and implementing.

A miR-137-XIAP axis contributes to the sensitivity of TRAIL-induced cell death in glioblastoma.

Glioblastoma (GBM) is the most lethal primary brain tumor in the central nervous system with limited therapeutic strategies to prolong the survival rate in clinic. TNF-related apoptosis-inducing ligand (TRAIL)-based strategy has been demonstrated to induce cell death in an extensive spectrum of tumor cells, including GBM, while a considerable proportion of malignant cells are resistant to TRAIL-induced apoptosis. MiR-137 is highly expressed in the brain, but significantly decreases with advanced progression of GBM. However, the functional link between miR-137 and TRAIL-induced apoptosis in GBM cells has not been established. Here, GBM cells were transfected with miR-137, and gene expression levels were examined by qRT-PCR and western blot. Apoptotic cells were measured by Annexin-V staining and TUNEL assay. Our data showed that miR-137 sensitizes GBM cells to the TRAIL-mediated apoptosis. Mechanistically, we identified that XIAP is a bona fide target of miR-137, which is essential for miR-137-regulated sensitivity of TRAIL-induced cell death in GBM cells. Finally, in a xenograft model, combined utilization of miR-137 and TRAIL potently suppresses tumor growth in vivo. Collectively, we demonstrate that a miR-137-XIAP axis is required for the sensitivity of TRAIL-induced cell death and shed a light on the avenue for the treatment of GBM.

Multistep approach to microscopic models for frustrated quantum magnets: the case of the natural mineral azurite.

The natural mineral azurite Cu(3)(CO(3))(2)(OH)(2) is a frustrated magnet displaying unusual and controversially discussed magnetic behavior. Motivated by the lack of a unified description for this system, we perform a theoretical study based on density functional theory as well as state-of-the-art numerical many-body calculations. We propose an effective generalized spin-1/2 diamond chain model which provides a consistent description of experiments: low-temperature magnetization, inelastic neutron scattering, nuclear magnetic resonance measurements, magnetic susceptibility as well as new specific heat measurements. With this study we demonstrate that the balanced combination of first principles with powerful many-body methods successfully describes the behavior of this frustrated material.

Inhibition of dermal fibrosis in self-assembled skin equivalents by undifferentiated keratinocytes.

BACKGROUND: Previous studies showed that keratinocyte plays a major role in dermal cell behavior and hypertrophic scar formation. Further investigations showed that keratinocytes derived from normal skin and hypertrophic scar have different effects on dermal fibroblasts. OBJECTIVE: To investigate the role of undifferentiated keratinocytes in epidermal-dermal interaction and dermal fibrosis. METHODS: A tissue-engineered model of self-assembled reconstructed skin was used in this study to mimic interactions between dermal and epidermal cells. Transmission electron microscope, RT and Western blot analysis were performed to show extracellular matrix morphology, collagen synthesis and associated factors expression changes. RESULTS: The dermal extracellular matrix co-cultured with undifferentiated keratinocytes was well distributed, collagen bundles were not seen, and the levels of collagen mRNA and protein expression declined to 46%, 20% of that in the presence of differentiated keratinocytes. Undifferentiated keratinocytes inhibited dermal fibrosis through down-regulation of TGFbeta1, promoting bFGF expression and desmosome formation. CONCLUSIONS: Undifferentiated keratinocytes have the ability to preserve normal epidermal-dermal interaction and inhibit dermal fibrosis. Absence or diminution of undifferentiated keratinocytes may take part in initiating events leading to pathological fibrosis.