Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 73
Filtrar
1.
Mol Carcinog ; 63(6): 1160-1173, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695641

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA) expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma de Células Escamosas , Neovascularização Patológica , Neoplasias Cutâneas , Raios Ultravioleta , Fator A de Crescimento do Endotélio Vascular , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Camundongos , Neovascularização Patológica/metabolismo , Linhagem Celular Tumoral , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Emodina/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Angiogênese
2.
Photodiagnosis Photodyn Ther ; 47: 104196, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710260

RESUMO

SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.


Assuntos
Apoptose , Autofagia , Células Endoteliais da Veia Umbilical Humana , Fotoquimioterapia , Fármacos Fotossensibilizantes , Sirolimo , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fotoquimioterapia/métodos , Autofagia/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Sirolimo/farmacologia , Hidroxicloroquina/farmacologia , Porfirinas/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
J Exp Bot ; 75(11): 3322-3336, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38506421

RESUMO

Modern tomatoes produce colorful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. Here, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci responsible for fruit development. The colorless peel of LBS fruits was caused by a 603 bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as STAY-GREEN 1 (SlSGR1) and PHYTOENE SYNTHASE 1 (SlPSY1). SGR1 and PSY1 co-suppression by RNAi converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were also identified in several wild tomatoes bearing green or gray ripe fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS, and transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii also failed to convert purple-flesh into red-flesh fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1, and SlSGR1 control fruit color in cultivated and some wild tomato species.


Assuntos
Alquil e Aril Transferases , Frutas , Geranil-Geranildifosfato Geranil-Geraniltransferase , Proteínas de Plantas , Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Geranil-Geranildifosfato Geranil-Geraniltransferase/genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Mutação , Plantas Geneticamente Modificadas/genética , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Heliyon ; 10(5): e27195, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38468954

RESUMO

Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38204456

RESUMO

Janus kinase (JAK) inhibitors are increasingly being used in dermatology due to their broad potential in managing both local and systemic inflammation. More recently, abrocitinib, an oral JAK 1 inhibitor, has shown promising clinical efficacy in the treatment of various skin disorders beyond moderate to severe atopic dermatitis (AD). We firstly presented three cases, each with diagnosis of pyoderma gangrenosum (PG), livedoid vasculopathy (LV), or hidradenitis suppurativa (HS), and conducted a comprehensive scoping review of the available literature on the use of abrocitinib in the treatment of diverse skin disorders. We summarized a total of 16 skin disorders, including our cases. The results indicated that abrocitinib, whether used as monotherapy or in combination with other treatments, was effective and well-tolerated in these disorders. These findings expanded the range of diseases for which abrocitinib may serve as an alternative therapeutic choice.

6.
Lab Invest ; 104(2): 100300, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38042496

RESUMO

Formalin-fixed paraffin-embedded (FFPE) tissues are the primary source of DNA for companion diagnostics (CDx) of cancers. Degradation of FFPE tissue DNA and inherent tumor heterogeneity constitute serious challenges in current CDx assays. To address these limitations, we introduced sequence artifact elimination and mutation enrichment to MeltArray, a highly multiplexed PCR approach, to establish an integrated protocol that provides accuracy, ease of use, and rapidness. Using PIK3CA mutations as a model, we established a MeltArray protocol that could eliminate sequence artifacts completely and enrich mutations from 23.5- to 59.4-fold via a single-reaction pretreatment step comprising uracil-DNA-glycosylase excision and PCR clamping. The entire protocol could identify 13 PIK3CA hotspot mutations of 0.05% to 0.5% mutant allele fractions within 5 hours. Evaluation of 106 breast cancer and 40 matched normal FFPE tissue samples showed that all 47 PIK3CA mutant samples were from the cancer tissue, and no false-positive results were detected in the normal samples. Further evaluation of 105 colorectal and 40 matched normal FFPE tissue samples revealed that 11 PIK3CA mutants were solely from the cancer sample. The detection results of our protocol were consistent with those of the droplet digital PCR assays that underwent sequence artifact elimination. Of the 60 colorectal samples with next-generation sequencing results, the MeltArray protocol detected 2 additional mutant samples with low mutant allele fractions. We conclude that the new protocol provides an improved alternative to current CDx assays for detecting tumor mutations in FFPE tissue DNA.


Assuntos
Artefatos , Neoplasias Colorretais , Humanos , Inclusão em Parafina , Mutação , Classe I de Fosfatidilinositol 3-Quinases/genética , Reação em Cadeia da Polimerase Multiplex , DNA , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Formaldeído
7.
World J Clin Cases ; 11(27): 6537-6542, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37900241

RESUMO

BACKGROUND: An intradermal nevus is a common skin tumour, and the classical method of removal has a risk of recurrence and scarring. It is a challenge for dermatologists to treat eyebrow intradermal nevi quickly and efficiently. This study focused on investigating the efficacy and safety of shearing combined with electrocautery and curettage in the treatment of eyebrow intradermal nevi. CASE SUMMARY: We describe two adult patients with eyebrow intradermal nevi treated by shearing combined with electrocautery and curettage. Both patients were followed up regularly after surgery. At follow-up, no recurrence of eyebrow intradermal nevus and no obvious scars or hypopigmentation were found in either patient. The results indicated that shearing combined with electrocautery and curettage could remove eyebrow intradermal nevus without side effects and confirmed the efficacy and safety of this modality for treating these skin lesions. CONCLUSION: Shearing combined with electrocautery and curettage has superior merits, including simple operation, good cosmetic effects, and high patient satisfaction, presenting great application potential for treating intracutaneous nevus.

8.
BMC Med ; 21(1): 230, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400844

RESUMO

BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.


Assuntos
Neurofibroma Plexiforme , Neurofibromatose 1 , Humanos , Adulto , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/patologia , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/patologia , Inibidores de Proteínas Quinases/uso terapêutico
9.
Antimicrob Agents Chemother ; 67(4): e0167922, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36943064

RESUMO

Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti-C. acnes compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against C. acnes (ATCC 6919 and HM-513) of 1 µg/mL. CD437 demonstrated an MBC of 2 µg/mL compared to up to 64 µg/mL for the retinoid adapalene and up to 16 µg/mL for tetracycline, which are commonly used clinically to treat acne. Membrane permeability assays demonstrated that exposure of C. acnes ATCC 6919 to CD437 damaged the integrity of C. acnes ATCC 6919 bacterial membranes, and this finding was confirmed with scanning electron microscopy. Additionally, CD437 downregulated the expression of C. acnes ATCC 6919 virulence factors, including the genes encoding Christie-Atkins-Munch-Petersen factor 1 (CAMP1), CAMP2, glycerol-ester hydrolase B (GehB), sialidase B, and neuraminidase. In a mouse skin infection model of C. acnes ATCC 6919, topical treatment with CD437 ameliorated skin lesions and reduced the bacterial burden in situ (P < 0.001). In human NHEK primary cells, CD437 reduced the transcriptional levels of the coding genes for inflammatory cytokines (interleukin-1α, ~10-fold; interleukin-6, ~20-fold; interleukin-8, ~30-fold; and tumor necrosis factor-alpha, ~6-fold) and downregulated the transcriptional levels of KRT10 (~10-fold), FLG (~4-fold), and TGM1 (~2-fold), indicating that CD437 can diminish inflammation and hyperkeratinization. In summary, CD437 deserves further attention for its dual function as a potential acne therapeutic that potentially acts on both the pathogen and the host.


Assuntos
Acne Vulgar , Retinoides , Camundongos , Animais , Humanos , Retinoides/metabolismo , Retinoides/uso terapêutico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Citocinas/metabolismo , Antibacterianos/uso terapêutico , Inflamação , Propionibacterium acnes
10.
Carbohydr Polym ; 305: 120549, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36737198

RESUMO

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.


Assuntos
Vitiligo , alfa-MSH , Humanos , alfa-MSH/farmacologia , Vitiligo/tratamento farmacológico , Dextranos , Hidrogéis , Melanócitos
13.
World J Clin Cases ; 10(35): 13064-13073, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36568998

RESUMO

BACKGROUND: We report on a case of Vibrio vulnificus (V. vulnificus) detected by metagenomics next-generation sequencing (mNGS) in a 53-year-old male patient with polymicrobial gas gangrene and successful treatment by surgery. This report raises awareness among dermatologists that when a patient is clinically suspected of a special type of pathogenic infection, the mNGS method should be preferred to identify the patient's pathogen infection as soon as possible and then take effective treatment in time to save patients' lives. CASE SUMMARY: A 53-year-old male who worked in the aquatic market complained of redness and swelling of the lower limbs, blisters and ulcers with fever for 3 d. We used mNGS to test the pathogens in ulcer secretions. The results were returned in 24 h and indicated: V. vulnificus, Fusobacterium necrophorum, Staphylococcus haemolyticus, Staphylococcus aureus, Streptococcus dysgalactiae and Klebsiella aerogenes. This patient was diagnosed with V. vulnificus infection. The emergency operation was performed immediately under combined lumbar and epidural anesthesia: Left leg expansion and exploration (August 10, 2021). After surgery, we continued to use piperacillin sodium tazobactam sodium 4.5 g every 8 h and levofloxacin 0.5 g for anti-infection treatment. The patient underwent further surgery under lumbar anesthesia on August 17, 2021 and August 31, 2021: Left leg deactivation and skin grafting, negative pressure closed drainage and right thigh skin removal. After treatment, the transplanted flap survived. CONCLUSION: We could confirm the diagnosis of Vibrio vulnificus infection within 24 h through mNGS detection and then immediately performed emergency surgery.

14.
Nat Commun ; 13(1): 5940, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209204

RESUMO

The domestication of tomato has led to striking variations in fruit morphology. Here, we show a genome-wide association study (GWAS) to understand the development of the fruit tip and describe a POINTED TIP (PT) gene that encodes a C2H2-type zinc finger transcription factor. A single nucleotide polymorphism is found to change a histidine (H) to an arginine (R) in the C2H2 domain of PT and the two alleles are referred to as PTH and PTR. Knocking out PTH leads to development of pointed tip fruit. PTH functions to suppress pointed tip formation by downregulating the transcription of FRUTFULL 2 (FUL2), which alters the auxin transport. Our evolutionary analysis and previous studies by others suggest that the PTR allele likely hitch-hiked along with other selected loci during the domestication process. This study uncovers variation in PT and molecular mechanism underlying fruit tip development in tomato.


Assuntos
Solanum lycopersicum , Arginina/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Histidina/genética , Ácidos Indolacéticos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética
15.
Photodiagnosis Photodyn Ther ; 40: 103053, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35932961

RESUMO

BACKGROUND: Traditional treatments for human papillomavirus-related cutaneous diseases include 5-aminolevulinic acid photodynamic therapy, cryotherapy, microwave ablation, and surgical resection. These treatment methods involvevarious adverse reactions; therefore, it remains necessary to explore new treatment methods. Dihydroartemisinin shows cytotoxic effects against several malignancies by producing reactive oxygen species, and heme environments reportedly enhance its activity. However, the underlying mechanismsare still unclear. Therefore, we investigated the mechanism of dihydroartemisininin inhuman papillomavirus-infected cells. METHODS: HeLa cells were treated with dihydroartemisinin, 5-aminolevulinic acid, and succinylacetone. The cell viability, apoptosis, mitochondrial membrane potential, and reactive oxygen species levels were investigated, and via western blotting analysis and polymerase chain reaction, dihydroartemisinin activity-related pathways were also determined. RESULTS: Dihydroartemisinin inhibited HeLa cell proliferation and promoted cell apoptosis via the Bax/Bcl-2-Caspase pathway in a concentration-dependent manner. The specific cytotoxicity toward HeLa cells was enhanced by the addition of 5-aminolevulinic acid, a clinically used heme-synthesis precursor, owing to an increase in heme levels. Conversely, following the addition of succinylacetone, a heme synthesis blocker, heme levels decreased. Furthermore, dihydroartemisinin significantly increased reactive oxygen species levels as intracellular heme synthesis increased. Moreover, photodynamic therapy following dihydroartemisinin and 5-aminolevulinic acid treatment further enhanced the cytotoxic effect of dihydroartemisinin on high-risk human papillomavirus-infected cells. CONCLUSIONS: Dihydroartemisinin exerts acytotoxic effect on high-risk human papillomavirus-infected cells by modulating heme levels via the Bax/Bcl-2-Caspase pathway, and the dihydroartemisinin, 5-aminolevulinic acid, photodynamic therapy combination treatment significantly enhanced its cytotoxic effect on human papillomavirus-infected cells.


Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Humanos , Ácido Aminolevulínico/farmacologia , Células HeLa , Caspases , Papillomavirus Humano , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Apoptose , Heme , Linhagem Celular Tumoral
16.
Burns Trauma ; 10: tkac013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547861

RESUMO

Background: A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids. Methods: We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments. Results: HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway. Conclusions: Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.

17.
Photodiagnosis Photodyn Ther ; 39: 102918, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35618257

RESUMO

BACKGROUND: Bowenoid papulosis (BP) is a rare infectious skin disease that occurs in sexually active young people. BP is associated with human papillomavirus (HPV)16 and 18 infections, spreads through sexual contact, and tends to become cancerous. Currently, there are different BP treatment methods, and few reports on the efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT). We compared the differences in the clearance and recurrence rates of BP between the ALA-PDT group and other groups, and explored methods to improve clinical effects and reduce lesion recurrence by combining clinical retrospective data. METHODS: We enrolled patients who were diagnosed with bowel papulosis" between January 1, 2009, and December 31, 2020. Patient information, such as ID number, hospitalization number, admission time, name, age, gender, telephone number, admission record, discharge record, outpatient medical history, HPV type analysis, histopathological examination, and treatment plan were recorded. Outcomes were obtained and recorded through outpatient visits, telephone, and online follow-ups from patients who had reached the treatment endpoint. We compared and evaluated the differences in lesion clearance rate, lesion recurrence rate, and patient satisfaction between the ALA-PDT group and other groups using statistical analysis. RESULTS: The lesion clearance rate of the ALA-PDT group was significantly higher than that of the control group, the lesion recurrence rate was lower than that of the control group, and patient satisfaction was higher than that of the control group. The lesion clearance rate of the ALA-PDT group was higher than that of the microwave and radiofrequency groups, the lesion recurrence rate of the ALA-PDT group was significantly lower than that of the microwave and radiofrequency groups, and patient satisfaction was significantly higher than that of the microwave and radiofrequency groups. In the lesions of patients with BP, in addition to HPV16 and HPV18 types, other types were also detected, and most of them were mixed types of HPV infection. Age, sex, and duration of disease were not risk factors that affected BP recurrence. CONCLUSIONS: ALA-PDT for BP has the advantages of high lesion clearance rate, low lesion recurrence rate, and high patient satisfaction. ALA-PDT is worthy of recommendation as a preferred treatment plan for the treatment of BP.


Assuntos
Carcinoma de Células Escamosas , Condiloma Acuminado , Infecções por Papillomavirus , Fotoquimioterapia , Lesões Pré-Cancerosas , Adolescente , Ácido Aminolevulínico , Carcinoma de Células Escamosas/tratamento farmacológico , Condiloma Acuminado/tratamento farmacológico , Seguimentos , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Lesões Pré-Cancerosas/tratamento farmacológico , Estudos Retrospectivos
18.
Plant Sci ; 318: 111206, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35351297

RESUMO

Reactive oxygen species (ROS) are inevitably generated in aerobic organisms as by-products of common metabolism and as the result of defense and development. ROS readily oxidizes methionine (Met) residues of proteins to form Met-R-sulfoxide or Met-S-sulfoxide (MetSO), resulting in protein inactivation or malfunction. Although it is known that MetSO can be reverted to Met by methionine sulfoxide reductase (Msr), the mechanism how Msr interacts with its target proteins is poorly understood. In this study, two target proteins of tomato MsrB2 (SlMsrB2), catalase 2 (CAT2) and the Rubisco small subunit RBCS3B, were identified. Silencing of SlMsrB2 by RNA interference (RNAi) in tomato led to decreased drought tolerance, accompanied by increased ROS accumulation and chlorophyll degradation. By contrast, overexpression of SlMsrB2 in tomato significantly reduced ROS accumulation and enhanced drought tolerance. Protein interaction analysis showed that SlMsrB2 interacts with CAT2 and RBCS3B in vitro and in planta. Silencing of CAT2 by RNAi and RBCS3B by virus-induced gene silencing (VIGS) resulted in development of pale green leaves and enhanced ROS accumulation in tomato plants. These results demonstrate that SlMsrB2 functions in drought tolerance and promotes chlorophyll accumulation by modulating ROS accumulation.


Assuntos
Solanum lycopersicum , Catalase , Clorofila/metabolismo , Secas , Solanum lycopersicum/metabolismo , Metionina Sulfóxido Redutases/química , Metionina Sulfóxido Redutases/genética , Metionina Sulfóxido Redutases/metabolismo , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética
19.
ACS Omega ; 7(9): 7777-7790, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35284714

RESUMO

The liquid nitrogen freeze-thaw (LN2-FT) method has been widely used to improve the coal permeability in the coalbed methane (CBM) production. However, the influence of moisture content on the permeability of coal treated by LN2-FT remains unclear, limiting the broad application of this technique. A novel seepage system was proposed to analyze the permeability evolution of anthracite coal samples treated by LN2-FT. Moreover, variations of the pore structure were analyzed using scanning electron microscopy (SEM), mercury intrusion porosimetry (MIP), and low-field NMR. The results showed that pores and fractures appeared on the coal surface after the LN2-FT treatment. As the moisture content of the coal increased, more pores and fractures tended to be formed during the LN2-FT treatment. The total pore volume, porosity, and average pore diameter of the anthracite coal after the treatment were 1.77, 2.44, and 5.58 times higher, respectively, than that of the raw coal. The change in the specific surface area exhibited three trends as the moisture content of the coal samples increased: a slow descent, a steady increase, and a rapid descent. Moreover, it was found that the LN2-FT treatment increased the connections between pores and fractures, improving gas migration in the coal. Furthermore, the LN2-FT treatment significantly increased the permeability of the anthracite coal samples. The higher the coal moisture, the higher the permeability of the coal samples after the LN2-FT treatment. Hence, the LN2-FT technique can substantially improve the permeability of coal reservoirs, providing essential information for the efficient utilization of CBM.

20.
J Exp Bot ; 73(1): 228-244, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34499170

RESUMO

Trichomes are specialized glandular or non-glandular structures that provide physical or chemical protection against insect and pathogen attack. Trichomes in Arabidopsis have been extensively studied as typical non-glandular structures. By contrast, the molecular mechanism underlying glandular trichome formation and elongation remains largely unknown. We previously demonstrated that Hair is essential for the formation of type I and type VI trichomes. Here, we found that overexpression of Hair increased the density and length of tomato trichomes. Biochemical assays revealed that Hair physically interacts with its close homolog SlZFP8-like (SlZFP8L), and SlZFP8L also directly interacts with Woolly. SlZFP8L-overexpressing plants showed increased trichome density and length. We further found that the expression of SlZFP6, which encodes a C2H2 zinc finger protein, is positively regulated by Hair. Using chromatin immunoprecipitation, yeast one-hybrid, and dual-luciferase assays we identified that SlZFP6 is a direct target of Hair. Similar to Hair and SlZFP8L, the overexpression of SlZFP6 also increased the density and length of tomato trichomes. Taken together, our results suggest that Hair interacts with SlZFP8-like to regulate the initiation and elongation of trichomes by modulating SlZFP6 expression in tomato.


Assuntos
Dedos de Zinco CYS2-HIS2 , Solanum lycopersicum , Solanum lycopersicum/genética , Tricomas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...