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1.
J Autoimmun ; 149: 103307, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39276627

RESUMO

Pemphigus is a severe autoimmune blistering disease characterized by acantholysis triggered by autoantibodies against desmoglein 1 and 3 (DSG1/3). Apoptosis plays a pivotal role in facilitating acantholysis, yet the precise underlying mechanism remains obscure. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to promote apoptosis and disrupt cell junctions, although its involvement in pemphigus pathogenesis remains ambiguous. Our study observed decreased DSG1/3 expression alongside increased TWEAK/fibroblast growth factor-inducible 14 (Fn14) expression and keratinocyte apoptosis in both lesional and perilesional skin. In vitro experiments revealed that TWEAK-stimulated keratinocytes exhibited enhanced apoptosis, STAT1 phosphorylation, and reduced intercellular DSG1/3 expression. Notably, bulk-RNA sequencing unveiled that CASPASE-3 was responsible for mediating the DSG1/3 depletion, as confirmed by direct interaction with DSG1/3 in a co-immunoprecipitation assay. Naloxone, known for preserving cellular adhesion and preventing cell death, effectively reduced apoptosis and restored DSG1/3 levels in TWEAK-stimulated keratinocytes. The anti-apoptotic properties of naloxone were further validated in a murine pemphigus model. Our findings elucidate that TWEAK facilitates keratinocyte apoptosis by augmenting caspase-3 activity, leading to DSG1/3 depletion and apoptosis in pemphigus. Importantly, naloxone can counter TWEAK-induced apoptosis in pemphigus pathogenesis, offering a potential therapeutic intervention.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39324269

RESUMO

Adenohypophysis-inducible sex hormones include prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These hormones influence the occurrence of lupus erythematosus by affecting the endocrine and immune systems. The present study analyzed the relationship between serum sex hormones and several cytokines in patients with systemic lupus erythematosus (SLE). Compared with the healthy controls, early-onset SLE female patients with menopause had higher PRL levels than the healthy controls and cutaneous lupus erythematosus (CLE) group. FSH levels were higher in male patients with SLE than in the healthy controls or CLE group. In SLE patients, the estradiol levels correlated negatively with interleukin (IL)-8. The levels of FSH versus IL-8, PRL versus IL-6, PRL versus tumor necrosis factor (TNF)-α, and LH versus IL-8 levels were moderately positively correlated. In conclusion, PRL, FSH, and LH are positively associated with IL-6, IL-8, and TNF-α in the sera from SLE patients, which indicates that sex hormone levels can serve as an indicator of disease activity during SLE diagnosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38841932

RESUMO

Background Hailey-Hailey disease (HHD) is a rare, autosomal dominant, hereditary skin disorder characterised by epidermal acantholysis. The HHD-associated gene ATPase calcium-transporting type 2C member 1 (ATP2C1) encodes the protein secretory pathway Ca2+ ATPase1 (SPCA1), playing a critical role in HHD pathogenesis. Aims We aimed to investigate the effect of ATP2C1 knockdown on keratinocytes that mimicked acantholysis in HHD. Methods Immunohistochemistry (IHC) was employed to evaluate the levels of cytoskeletal and tight junction proteins such as SPCA1, P-cofilin, F-actin, claudins, occludin, and zonula occludens 1 in the skin biopsies of patients with HHD. Subsequently, the expression of these proteins in cultured ATP2C1 knockdown keratinocytes was analysed using Western blotting and immunofluorescence. Furthermore, we assessed the proliferation, apoptosis, and intracellular Ca2+ concentrations in the ATP2C1-knocked keratinocytes. Results The results showed decreased levels of these proteins (SPCA1, P-cofilin, F-actin, claudins, occluding, and zonula occludens 1) in HHD skin lesions. Moreover, their levels decreased in human keratinocytes transfected with ATP2C1 short hairpin RNA, accompanied by morphological acantholysis. Furthermore, the proliferation and apoptosis of the keratinocytes, as well as intracellular calcium concentrations in these cells, were not affected. Limitations The limitations of this study are the absence of animal experiments and the failure to explore the relationship between skeletal and tight junction proteins. Conclusion The present study indicated that ATP2C1 inhibition led to abnormal levels of the cytoskeletal and tight junction proteins in the keratinocytes. Therefore, keratinocytes can mimic HHD-like acantholysis and serve as an in vitro model, helping develop treatment strategies against HHD.

5.
Polymers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891496

RESUMO

Dielectric elastomer is a kind of electronic electroactive polymer, which plays an important role in the application of soft robots and flexible electronics. In this study, an all-organic polyaniline/copper phthalocyanine/silicone rubber (PANI/CuPc/PDMS) dielectric composite with superior comprehensive properties was prepared by manipulating the arrangement of filler in a polymer matrix assisted by electric fields. Both CuPc particles and PANI particles can form network structures in the PDMS matrix by self-assembly under electric fields, which can enhance the dielectric properties of the composites at low filler content. The dielectric constant of the assembled PANI/CuPc/PDMS composites can reach up to 140 at 100 Hz when the content of CuPc and PANI particles is 4 wt% and 2.5 wt%, respectively. Moreover, the elastic modulus of the composites remains below 2 MPa, which is important for electro-deforming. The strain of assembled PANI/CuPc/PDMS three-phase composites at low electric field strength (2 kV/mm) can increase up to five times the composites with randomly dispersed particles, which makes this composite have potential application in the field of soft robots and flexible electronics.

6.
Photodiagnosis Photodyn Ther ; 48: 104227, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38821237

RESUMO

BACKGROUND: Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS. METHODS: Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted. RESULTS: Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT. CONCLUSION: ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.


Assuntos
Ácido Aminolevulínico , Celulite (Flegmão) , Fotoquimioterapia , Fármacos Fotossensibilizantes , Dermatoses do Couro Cabeludo , Humanos , Ácido Aminolevulínico/uso terapêutico , Masculino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatopatias Genéticas/tratamento farmacológico , Idoso , Couro Cabeludo
7.
J Interferon Cytokine Res ; 44(6): 260-270, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563809

RESUMO

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.


Assuntos
Proteína Forkhead Box O3 , Inflamação , Interferon-alfa , Psoríase , Animais , Feminino , Camundongos , Modelos Animais de Doenças , Proteína Forkhead Box O3/metabolismo , Imiquimode , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/metabolismo , Interferon-alfa/metabolismo , Fosforilação/efeitos dos fármacos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/patologia , Psoríase/metabolismo , Psoríase/imunologia
8.
J Dermatol Sci ; 114(1): 2-12, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514279

RESUMO

BACKGROUND: Keratinocyte dysdifferentiation and proinflammatory cytokine production play a central role in psoriatic inflammation. According to recent studies, the Rh family C glycoprotein (RHCG) enhances cell proliferation and disrupts cell differentiation. However, the specific role of RHCG psoriasis development remains unclear. OBJECTIVE: We here explored the effect of RHCG on keratinocytes under psoriatic inflammation. METHODS: The cell counting kit­8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction. RESULTS: Both RHCG mRNA and protein levels increased in psoriatic skin. Notably, cultured keratinocytes treated with an M5 cocktail, which mimics psoriatic inflammation, exhibited higher RHCG expression. Furthermore, RHCG overexpression promoted keratinocyte proliferation, accompanied by an increase in the production of interleukin (IL)-1ß, IL-6, and IL-8, and tumor necrosis factor-α. RHCG overexpression also resulted in higher expression of keratin 17, a differentiation marker. Conversely, RHCG gene knockdown reduced keratinocyte proliferation and cytokine secretion. RHCG inhibition in cells recovered both keratin 1 and loricrin expression. Additionally, RHCG overexpression facilitated the phosphorylation of nuclear factor-kappa B and extracellular signal-regulated protein kinase signaling pathways. Importantly, when these signaling pathways were inhibited, the effect of RHCG on keratinocytes was attenuated. CONCLUSION: These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment.


Assuntos
Diferenciação Celular , Proliferação de Células , Citocinas , Queratinócitos , Psoríase , Humanos , Queratinócitos/metabolismo , Psoríase/patologia , Psoríase/imunologia , Psoríase/metabolismo , Citocinas/metabolismo , Feminino , Masculino , Células Cultivadas , Pele/patologia , Pele/imunologia , Pele/metabolismo , Pele/citologia , Adulto , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transdução de Sinais
9.
Stem Cell Res Ther ; 15(1): 76, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38475896

RESUMO

BACKGROUND: A traditional view is that stem cells (SCs) divide slowly. Meanwhile, both embryonic and pluripotent SCs display a shorter cell cycle duration (CCD) in comparison to more committed progenitors (CPs). METHODS: We examined the in vitro proliferation and cycling behavior of somatic adult human cells using live cell imaging of passage zero keratinocytes and single-cell RNA sequencing. RESULTS: We found two populations of keratinocytes: those with short CCD and protracted near exponential growth, and those with long CCD and terminal differentiation. Applying the ergodic principle, the comparative numbers of cycling cells in S phase in an enriched population of SCs confirmed a shorter CCD than CPs. Further, analysis of single-cell RNA sequencing of cycling adult human keratinocyte SCs and CPs indicated a shortening of both G1 and G2M phases in the SC. CONCLUSIONS: Contrary to the pervasive paradigm, SCs progress through cell cycle more quickly than more differentiated dividing CPs. Thus, somatic human adult keratinocyte SCs may divide infrequently, but divide rapidly when they divide. Additionally, it was found that SC-like proliferation persisted in vitro.


Assuntos
Células-Tronco Pluripotentes , Adulto , Humanos , Proliferação de Células , Ciclo Celular , Divisão Celular , Diferenciação Celular , Fenótipo , Queratinócitos/metabolismo
10.
J Autoimmun ; 145: 103205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493673

RESUMO

Peptide ALW (ALWPPNLHAWVP) targeting anti-dsDNA antibodies has shown promising therapeutic effects in alleviating lupus nephritis, but is potentially limited by poor stability and non-kidney targeting. We recently developed a D-form modified ALW, called D-ALW, which has the capacity to widely inhibit pathogenic polyclonal anti-dsDNA antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles to enhance good kidney-targeting ability and extend half-life. Here, we demonstrate that the D-form modified ALW maintains higher binding and inhibition efficiencies and achieves higher stability. Most importantly, D-ALW nanoparticles exhibit excellent kidney-targeting ability and prolong the half-life of the peptides in BALB/c mice. Additionally, compared to D-ALW, D-ALW nanoparticles significantly reduce the glomerular deposition of IgG and C3, improve renal histopathologies, such as glomerular proliferation and inflammatory cells infiltration, and markedly prolong lifespan in MRL/lpr lupus-prone mice. Overall, these results establish that the D-ALW nanoparticles offer synergistic benefits in both safety and efficacy, providing long-term renal preservation and treatment advantages in lupus nephritis.


Assuntos
Anticorpos Antinucleares , Modelos Animais de Doenças , Nefrite Lúpica , Camundongos Endogâmicos MRL lpr , Nanopartículas , Animais , Nefrite Lúpica/imunologia , Nefrite Lúpica/tratamento farmacológico , Camundongos , Anticorpos Antinucleares/imunologia , Nanopartículas/química , Feminino , Camundongos Endogâmicos BALB C , Rim/patologia , Rim/metabolismo , Peptídeos/química , Peptídeos/imunologia , Imunoglobulina G/imunologia , Humanos
11.
Nanotechnology ; 35(29)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38154130

RESUMO

We successfully fabricated two-dimensional metallic CoBi nanoislands on SrTiO3(001) substrate by molecular beam epitaxy, and systematically investigated their electronic structures by scanning tunneling microscopy and spectroscopyin situat 4.2 K. Coulomb blockade and Coulomb staircases with discrete and well-separated levels are observed for the individual nanoisland, which is attributed to single-electron tunneling via two tunnel junction barriers. They are in excellent agreement with the simulations based on orthodox theory. Furthermore, we demonstrated that the Coulomb blockade becomes weaker with increasing temperature and almost disappears at ∼22 K in our variable temperature experiment, and its full-width at half-maximum of dI/dVpeaks with temperature is ∼6 mV. Our results provide a new platform for designing single-electron transistors that have potential applications in future microelectronics.

12.
ACS Nano ; 17(20): 19903-19913, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37801700

RESUMO

Designing a solid-state electrolyte that satisfies the operating requirements of solid-state batteries is key to solid-state battery applications. The consensus is that solid-state electrolytes need to allow fast ion transport, while providing better interfacial compatibility and mechanical tolerance. Herein, a simple but effective strategy is proposed, combining hard and soft component polymer systems, to exploit a solid polymer electrolyte (SPE) with a 3D network via an in situ graft polymerization. The 3D structure is constructed by a hard cellulose nanocrystal (CNC) as the skeleton and a soft polyacrylonitrile (PAN) as the filler through a dry-processing method. The reported systems have several advantages, including ease of processing, only requiring using an exceedingly small amount of solvent, light weight (ρ = 1.2 g cm-3), excellent mechanical stability (tensile strength of 9.5 MPa), and high ionic conductivity (3.9 × 10-4 S cm-1, 18 °C) and migration number (tLi+ = 0.8). In particular, the high conductivity is enabled: the efficient Li+ transportation path constructed between CNC-PAN powders and abundant sulfonate radicals and hydroxyl groups on the CNC surface acts as the bridge of Li+ transition. When the CNCs are grafted onto the PAN polymer, the dipole-dipole interaction between the nitrile groups of the PAN and the hydroxyl groups of the CNCs can help to improve the mechanical stability and ionic conductivity of the SPE. Moreover, a tightly formed interface between SPE and LiFePO4 (LFP)/carbon black/SPE cathode can be achieved in an assembled solid-state battery by hot pressing, thus further enhancing the battery's performance.

13.
Int Arch Allergy Immunol ; 184(12): 1184-1197, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37703833

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Microbial infection, immune system dysfunction, and skin barrier defunctionalization have been regarded as the central events in AD pathogenesis. Cold atmospheric plasma (CAP) is an unbound system composed of many free electrons, ions, and neutral particles, with macroscopic time and spatial scales. Based on dielectric barrier discharge, glow discharge, corona discharge, or arch discharge, CAP is generated at normal atmospheric pressure. Its special physical properties maintain its temperature at 20°C-40°C, combining the advantages of high safety and strong ionic activity. CAP has been tentatively used in inflammatory or pruritic skin disorders such as psoriasis, pruritus, and ichthyosis. Increasing data suggest that CAP can attack the microbial structure due to its unique effects, such as heat, ultraviolet radiation, and free radicals, resulting in its inactivation. Meanwhile, CAP regulates reactive oxygen species and reactive nitrogen species in and out of the cells, thereby improving cell immunocompetence. In addition, CAP has a beneficial effect on the skin barrier function via changing the skin lipid contents and increasing the skin permeability to drugs. This review summarizes the potential effects of CAP on the major pathogenic causes of AD and discusses the safety of CAP application in dermatology in order to expand the clinical application value of CAP to AD.


Assuntos
Dermatite Atópica , Gases em Plasma , Dermatopatias , Humanos , Dermatite Atópica/terapia , Gases em Plasma/uso terapêutico , Gases em Plasma/química , Raios Ultravioleta , Pele
14.
mSphere ; 8(4): e0007023, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37366641

RESUMO

Systemic lupus erythematosus (SLE), characterized by persistent inflammation, is a complex autoimmune disorder that affects all organs, challenging clinical treatment. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Modulating the gut microbiome is proposed as a promising approach for fine-running parts of the immune system, relieving systematic inflammation in multiple diseases. This study demonstrated that the administration of Akkermansia muciniphila and Lactobacillus plantarum contributed to an anti-inflammatory environment by decreasing IL-6 and IL-17 and increasing IL-10 levels in the circulation. The treatment of A. muciniphila and L. plantarum restored the intestinal barrier integrity to a different extent. In addition, both strains reduced the deposit of IgG in the kidney and improved renal function significantly. Further studies revealed distinct remodeling roles of A. muciniphila and L. plantarum administration on the gut microbiome. This work demonstrated essential mechanisms of how A. muciniphila and L. plantarum remodel gut microbiota and regulate the immune responses in the SLE mice model. IMPORTANCE Several pieces of research have demonstrated that certain probiotic strains contribute to regulating excessive inflammation and restoring tolerances in the SLE animal model. More animal trials combined with clinical studies are urgently needed to further elucidate the mechanisms for the effect of specific probiotic bacteria in preventing SLE symptoms and developing novel therapeutic targets. In this study, we explored the role of A. muciniphila and L. plantarum in ameliorating the SLE disease activity. Both A. muciniphila and L. plantarum treatment relieved the systemic inflammation and improved renal function in the SLE mouse model. We demonstrated that A. muciniphila and L. plantarum contributed to an anti-inflammatory environment by regulating cytokine levels in the circulation, restoring the intestinal barrier integrity, and remodeling the gut microbiome, however, to a different extent.


Assuntos
Microbioma Gastrointestinal , Lactobacillus plantarum , Lúpus Eritematoso Sistêmico , Animais , Camundongos , Lúpus Eritematoso Sistêmico/terapia , Verrucomicrobia , Inflamação/terapia , Anti-Inflamatórios , Imunidade
15.
Polymers (Basel) ; 15(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37177149

RESUMO

According to the demand for high-performance fibers for high-latitude ocean exploration and development, this paper selects representative products of high-performance liquid crystal fibers: thermotropic liquid crystal polymer fibers (TLCP) and poly p-phenylene terephthalamide (PPTA) fibers. Through a series of freeze-thaw (F-T) experiments for simulating a real, cold marine environment, we then measure the retention of mechanical properties of these two kinds of fibers. Before that, due to the difference in their chemical structures, we tested their Yang-Laplace contact angle (YLCA) and water absorption; the results suggested that PPTA fibers would absorb more moisture. Surprisingly, then, compared with thermotropic liquid crystal polymer (TLCP) fibers, the retention of the mechanical properties of poly p-phenylene terephthalamide (PPTA) fibers decreased by around 25% after the F-T experiments. The Fourier-transformed infrared (FT-IR) analysis, the attenuated total reflection (ATR) accessory analysis and the degree of crystal orientation measured by two-dimensional wide-angle X-ray diffraction (2D-WAXD) confirm that no changes in the chemical and the orientation structure of the crystal region of the fibers occurred after they underwent the F-T cycles. However, as observed by scanning electron microscopy (SEM), there are microcracks of various extents on the surface of the PPTA fibers, but they do not appear on the surface of TLCP fibers. It is obvious that these microcracks will lead to the loss of mechanical properties; we infer that the moisture absorbed by the PPTA fibers freezes below the freezing point, and the volume expansion of the ice causes the collapse of the microfibrillar structure. The two sorts of fibers subjected to the F-T experiments are immersed in a sodium chloride solution, and the amount of water infiltrated into the PPTA microfibrillar structure is evaluated according to the content of sodium ions in the fiber surface and subsurface layers through X-ray spectroscopy (EDS) elemental analysis. From the above analysis, we found that TLCP fibers can more effectively meet the operating standards of the severe and cold marine environment.

17.
Clin Cosmet Investig Dermatol ; 16: 429-442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817641

RESUMO

Melasma is a common acquired disorder of pigmentation that negatively impacts quality of life. Present treatments show poor therapeutic effect with frequent recurrence. This in large part is due to the currently limited understanding of the disease's etiology. It is urgent to elucidate the pathogenesis of melasma to further the discovery of new therapeutic strategies. Recent studies show that melasma is triggered or aggravated by a variety of factors, including genetic susceptibility, ultraviolet radiation, and sex hormone dysregulation. Ultraviolet B radiation upregulates the expression of several melanocyte-specific genes and stimulates the release of key factors that participate in the synthesis of melanin. There is a significant increase in melanin in both the epidermal and dermal layers of affected skin, possibly due to abnormalities in crosstalk between the melanocytes and other cells. Melanogenesis is regulated through various signaling networks including the Wnt/ß-catenin, PI3K/Akt, cAMP/PKA, and SCF/c-kit-mediated signaling pathways. In addition, inflammatory mediators, oxidative stress, neuroactive molecules, sebocytes, etc, have also been proved to be related to the pathogenesis of melasma. This review provides a comprehensive update on the current understanding of the pathogenesis of melasma.

18.
J Inflamm Res ; 16: 453-465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761905

RESUMO

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex pathogenesis, the treatment of which relies exclusively on the use of immunosuppressants. Increased oxidative stress is involved in causing inflammatory and cellular defects in the pathogenesis of SLE. Various inflammatory and cellular markers including oxidative modifications of proteins, lipids, and DNA contribute to immune system dysregulation and trigger an aggressive autoimmune attack through molecular mechanisms like enhanced NETosis, mTOR pathway activation, and imbalanced T-cell differentiation. Accordingly, the detection of inflammatory and cellular markers is important for providing an accurate assessment of the extent of oxidative stress. Oxidative stress also reduces DNA methylation, thus allowing the increased expression of affected genes. As a result, pharmacological approaches targeting oxidative stress yield promising results in treating patients with SLE. The purpose of this review is to examine the involvement of oxidative stress in the pathogenesis and management of SLE.

19.
Front Chem ; 11: 1094574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778032

RESUMO

Thermally activated delayed fluorescence (TADF) molecules have a theoretical 100% photoluminescence quantum yield in comparison with traditional fluorescent materials, leading to broad application in organic light-emitting diode (OLED). However, the application of TADF molecules with conjugated donor-acceptor structures in blue OLED remains a challenge due to their generally narrow energy gap between frontier molecular orbitals. Recently, a strategy has been approved in the improvement of the performance in TADF, in which void-carbon atoms between donor and acceptor fragments (donor-void-acceptor (D-v-A)) could regulate blue light emission. In this study, we first select three reported isomers followed by two proposed D-v-A TADF isomers to verify the feasibility of the void-carbon strategy through evaluation of the electronic structures in the excited state and photophysical properties. We further proposed a series of TADF molecules by replacing different donor and acceptor fragments to assess the applicability of the void-carbon strategy from the aspect of simulations in electronic structures, different properties of donor and acceptor fragments, photophysical properties, and analysis in the molecular conjugation. The results indicate that void-carbon strategy has conditional feasibility and applicability. Donor-acceptor molecular properties could be tuned through void-carbon strategy on aromatic acceptor fragments during the selection of promising candidates of TADF molecules. However, the void-carbon strategy does not work for the molecules with antiaromatic acceptor fragments, where the steric hindrance of the molecules plays a dominant role. Our work provides insightful guidance for the design of the blue-emission TADF molecules.

20.
Eur J Cell Biol ; 102(2): 151290, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36709605

RESUMO

Overabundance of the extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. TWEAK is a weak apoptosis inducer, and it plays a critical role in pathological tissue remodeling via its receptor, Fn14. However, the role of TWEAK/Fn14 signaling in the pathogenesis of keloids has not been investigated. In this study, we confirmed the overexpression levels of TWEAK and Fn14 in clinical keloid tissue specimens and primary KFs. The extracellular matrix (ECM)-related genes were also evaluated between primary KFs and their normal counterparts to determine the factors leading to the formation or development of keloids. Unexpectedly, exogenous TWEAK significantly reduced the levels of collagen I and collagen III, as well as alpha-smooth muscle actin (α-SMA). Additionally, TWEAK promoted MMPs expression and apoptosis activity of KFs. Furthermore, we verified that the inhibitory effect of TWEAK on KFs is through down-regulation of Polo-like kinase 5, which modulates cell differentiation and apoptosis. The TWEAK-Fn14 axis seems to be a secondary, although less effective, compensatory mechanism to increase the catabolic functions of fibroblasts in an attempt to further decrease the accumulation of collagen. DATA AVAILABILITY: All data generated or analyzed during this study are included in this published article (and its Supporting Information files).


Assuntos
Queloide , Humanos , Queloide/genética , Queloide/metabolismo , Queloide/patologia , Matriz Extracelular/metabolismo , Transdução de Sinais , Colágeno/metabolismo , Colágeno/farmacologia , Fibroblastos/metabolismo
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