Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Indian J Dermatol ; 69(4): 301-305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296682

RESUMO

Context: Isotretinoin is commonly prescribed for the treatment of acne. However, its association with inflammatory bowel disease (IBD) could not be confirmed due to inconsistencies in the literature. Furthermore, no related study has been conducted on an Asian population. Aims: The aim of this study was to investigate the association between isotretinoin and inflammatory bowel disease. Methods and Material: A nationwide, population-based, case-control study using the National Health Insurance Service database of South Korea was conducted. The case group comprised 107,434 patients with IBD, while the control group comprised 393,830 patients who were matched using a 1:4 propensity score. Data on isotretinoin exposure within the previous 5 years were extracted, and a multivariable-adjusted, conditional, logistic, regression analysis was performed. Results: After adjusting for age, sex, underlying disease, the Charlson co-morbidity index, and tetracycline use, a significant association between isotretinoin exposure and IBD was found, with an odds ratio of 1.20 (95% confidence interval, 1.10-1.30). Furthermore, the association appeared to become stronger with longer exposure, more of a cumulative dose, and a longer time since the first exposure. When analyzed separately for ulcerative colitis and Crohn's disease, isotretinoin exposure was significantly associated with both diseases. Conclusions: Our study reveals a dose-response relationship between isotretinoin exposure and IBD risk in an Asian population. Healthcare professionals should be aware of the association and consider alternative medications for acne treatment, particularly in patients who are at a higher risk of developing IBD.

3.
Int J Dermatol ; 63(6): 780-786, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38214207

RESUMO

BACKGROUND: Palmoplantar pustulosis (PPP) and pompholyx are chronic diseases characterized by pustules and vesicles on the palms and soles. These disorders often have similar clinicopathological features, which lead to diagnostic difficulties. We aimed to investigate the expression patterns of keratins and involucrin in PPP and pompholyx using immunohistochemical staining. METHODS: Skin biopsies from patients with PPP (n = 40) and pompholyx (n = 22) were immunohistochemically analyzed for Keratin 5, 9, 14, and involucrin expression. RESULTS: K5 expression was higher in PPP than in pompholyx, with diffusely positive expression in the basal, spinous, and granular layers. K14 expression did not differ between groups. K9 expression was observed near the pompholyx vesicle (P = 0.014) and stratum spinosum (P < 0.001) but was almost absent around PPP pustules. Involucrin expression was diffused around the PPP pustules and partially around the pompholyx vesicles, but without statistical significance (P = 0.123). Involucrin expression was elevated in the basal layer of the PPP compared with that in the pompholyx (P = 0.023). CONCLUSION: PPP and pompholyx exhibited distinctive differentiation in the expression of K5, K9, and involucrin.


Assuntos
Imuno-Histoquímica , Queratinas , Precursores de Proteínas , Psoríase , Humanos , Precursores de Proteínas/metabolismo , Precursores de Proteínas/análise , Psoríase/metabolismo , Psoríase/patologia , Psoríase/diagnóstico , Masculino , Feminino , Queratinas/metabolismo , Queratinas/análise , Pessoa de Meia-Idade , Adulto , Diagnóstico Diferencial , Idoso , Adulto Jovem , Eczema Disidrótico/diagnóstico , Eczema Disidrótico/metabolismo , Eczema Disidrótico/patologia , Biópsia , Adolescente , Pele/patologia , Pele/metabolismo , Queratina-9/metabolismo , Queratina-9/análise , Queratina-14/metabolismo , Queratina-14/análise
5.
Front Immunol ; 14: 1290191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035074

RESUMO

Macrophages are highly heterogeneous immune cells with a role in maintaining tissue homeostasis, especially in activating the defense response to bacterial infection. Using flow cytometric and single-cell RNA-sequencing analyses of peritoneal cells, we here show that small peritoneal macrophage and immature macrophage populations are enriched in histamine-deficient (Hdc -/-) mice, characterized by a CD11bmiF4/80loCCR2+MHCIIhi and CD11bloF4/80miTHBS1+IL-1α+ phenotype, respectively. Molecular characterization revealed that immature macrophages represent an abnormally differentiated form of large peritoneal macrophages with strong inflammatory properties. Furthermore, deficiency in histamine signaling resulted in significant impairment of the phagocytic activity of peritoneal macrophage populations, conferring high susceptibility to bacterial infection. Collectively, this study reveals the importance of histamine signaling in macrophage differentiation at the molecular level to maintain tissue homeostasis, offering a potential therapeutic target for bacterial infection-mediated diseases.


Assuntos
Histamina , Macrófagos , Camundongos , Animais , Macrófagos Peritoneais , Diferenciação Celular , Fagócitos
8.
Cell Mol Gastroenterol Hepatol ; 16(3): 411-429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207801

RESUMO

BACKGROUND & AIMS: Fibrosis development in ulcerative colitis is associated directly with the severity of mucosal inflammation, which increases the risk of colorectal cancer. The transforming growth factor-ß (TGF-ß) signaling pathway is an important source of tissue fibrogenesis, which is stimulated directly by reactive oxygen species produced from nicotinamide adenine dinucleotide phosphate oxidases (NOX). Among members of the NOX family, NOX4 expression is up-regulated in patients with fibrostenotic Crohn's disease (CD) and in dextran sulfate sodium (DSS)-induced murine colitis. The aim of this study was to determine whether NOX4 plays a role in fibrogenesis during inflammation in the colon using a mouse model. METHODS: Acute and recovery models of colonic inflammation were performed by DSS administration to newly generated Nox4-/- mice. Pathologic analysis of colon tissues was performed, including detection of immune cells, proliferation, and fibrotic and inflammatory markers. RNA sequencing was performed to detect differentially expressed genes between Nox4-/- and wild-type mice in both the untreated and DSS-treated conditions, followed by functional enrichment analysis to explore the molecular mechanisms contributing to pathologic differences during DSS-induced colitis and after recovery. RESULTS: Nox4-/- mice showed increased endogenous TGF-ß signaling in the colon, increased reactive oxygen species levels, intensive inflammation, and an increased fibrotic region after DSS treatment compared with wild-type mice. Bulk RNA sequencing confirmed involvement of canonical TGF-ß signaling in fibrogenesis of the DSS-induced colitis model. Up-regulation of TGF-ß signaling affects collagen activation and T-cell lineage commitment, increasing the susceptibility for inflammation. CONCLUSIONS: Nox4 protects against injury and plays a crucial role in fibrogenesis in DSS-induced colitis through canonical TGF-ß signaling regulation, highlighting a new treatment target.


Assuntos
Colite , Animais , Camundongos , Sulfato de Dextrana/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Colite/patologia , Fibrose , Fator de Crescimento Transformador beta , Inflamação , NADPH Oxidase 4/genética
9.
Cell Mol Gastroenterol Hepatol ; 15(1): 213-236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36167263

RESUMO

BACKGROUND & AIMS: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. METHODS: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow-transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. RESULTS: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. CONCLUSIONS: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.


Assuntos
Diferenciação Celular , Histamina , Macrófagos , Estômago , Animais , Camundongos , Histamina/fisiologia , Histidina Descarboxilase/genética , Estômago/microbiologia , Síndrome da Alça Cega , Camundongos Knockout
10.
Microbiome ; 10(1): 238, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36567320

RESUMO

BACKGROUND: Aging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged. RESULTS: As the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription of Dbn1 was most upregulated and DBN1-expressing cells increased twice. Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration. CONCLUSIONS: We revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin. Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Microbiota , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Envelhecimento/fisiologia , Transplante de Microbiota Fecal , Aptidão Física , Camundongos Endogâmicos C57BL
11.
Biosens Bioelectron ; 216: 114612, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35952434

RESUMO

Theranostic, which integrates the diagnosis and tumor treatment in tandem, is an emerging strategy in cancer treatment. Here, we report a novel and unique theranostic nanoparticle, HBCP NP, based on hexa-BODIPY cyclophosphazene (HBCP). Due to the unique bulky molecular structure of HBCP, this nanoparticle can simultaneously perform near-infrared (NIR) fluorescence imaging and photoacoustic imaging (PAI). Interestingly, since reactive oxygen species (ROS) generation of HBCP NPs is completely inhibited, 'safe' fluorescence imaging is possible without the risk of cell damage even under laser irradiation. Finally, NIR fluorescence imaging and PAI in 4T1 tumor-bearing mice demonstrated selective accumulation of HBCP NPs at tumor sites. In addition, HBCP NPs exhibited excellent photothermal effects under high-power laser irradiation, achieving effective tumor growth inhibition.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Animais , Compostos de Boro , Linhagem Celular Tumoral , Hexosaminidase A , Camundongos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Técnicas Fotoacústicas/métodos , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica/métodos
13.
NPJ Precis Oncol ; 6(1): 9, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087207

RESUMO

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

14.
Biomol Ther (Seoul) ; 30(2): 126-136, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580237

RESUMO

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

15.
Gut ; 71(7): 1266-1276, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34389621

RESUMO

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Microbiota , Neoplasias Gástricas , Animais , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/patologia , Humanos , Hiperplasia/patologia , Metaplasia/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Gástricas/patologia
16.
Gastroenterology ; 161(3): 953-967.e15, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116028

RESUMO

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.


Assuntos
Transformação Celular Neoplásica/metabolismo , Mucosa Gástrica/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-33/metabolismo , Lesões Pré-Cancerosas/metabolismo , Neoplasias Gástricas/metabolismo , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Animais , Atrofia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Mucosa Gástrica/ultraestrutura , Perfilação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-33/genética , Macrófagos/metabolismo , Metaplasia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transcriptoma , Regulação para Cima , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/genética
17.
Cancer Lett ; 495: 145-155, 2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-32987137

RESUMO

Approximately 70% of breast cancers are estrogen receptor (ER)-positive and treated with endocrine therapy. A commonly used treatment agent, tamoxifen, shows high efficacy for improving prognosis. However, approximately one-third of patients treated with tamoxifen develop resistance to this drug. Here, we investigated the function of general control non-derepressible 5 (GCN5) and its downstream effectors in tamoxifen-resistant (TamR) breast cancer. TamR-MCF7 breast cancer cells maintained high GCN5 levels due to its attenuated proteasomal degradation. GCN5 overexpression upregulated amplified in breast cancer 1 (AIB1) expression, resulting in decreased p53 stability and tamoxifen resistance. Conversely, the sensitivity of GCN5-AIB1-overexpressing MCF7 cells to tamoxifen was restored by forced p53 expression. An in vivo study demonstrated a positive correlation between GCN5 and AIB1 and their contribution to tamoxifen resistance. We concluded that GCN5 promotes AIB1 expression and tamoxifen resistance in breast cancer by reducing p53 levels, suggesting the utility of GCN5 and its downstream effectors as therapeutic targets to either prevent or overcome tamoxifen resistance in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Tamoxifeno/administração & dosagem , Regulação para Cima , Fatores de Transcrição de p300-CBP/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos , Transplante de Neoplasias , Prognóstico , Receptores de Estrogênio/metabolismo , Tamoxifeno/farmacologia , Proteína Supressora de Tumor p53/metabolismo
18.
BMC Cancer ; 20(1): 724, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758183

RESUMO

BACKGROUND: Breast tumor initiating cells (BTIC) are stem-like cells that initiate and sustain tumor growth, and drive disease recurrence. Identifying therapies targeting BTIC has been hindered due primarily to their scarcity in tumors. We previously reported that BTIC frequency ranges between 15% and 50% in multiple mammary tumors of 3 different transgenic mouse models of breast cancer and that this frequency is maintained in tumor cell populations cultured in serum-free, chemically defined media as non-adherent tumorspheres. The latter enabled high-throughput screening of small molecules for their capacity to affect BTIC survival. Antagonists of several serotonin receptors (5-HTRs) were among the hit compounds. The most potent compound we identified, SB-699551, selectively binds to 5-HT5A, a Gαi/o protein coupled receptor (GPCR). METHODS: We evaluated the activity of structurally unrelated selective 5-HT5A antagonists using multiple orthogonal assays of BTIC frequency. Thereafter we used a phosphoproteomic approach to uncover the mechanism of action of SB-699551. To validate the molecular target of the antagonists, we used the CRISPR-Cas9 gene editing technology to conditionally knockout HTR5A in a breast tumor cell line. RESULTS: We found that selective antagonists of 5-HT5A reduced the frequency of tumorsphere initiating cells residing in breast tumor cell lines and those of patient-derived xenografts (PDXs) that we established. The most potent compound among those tested, SB-699551, reduced the frequency of BTIC in ex vivo assays and acted in concert with chemotherapy to shrink human breast tumor xenografts in vivo. Our phosphoproteomic experiments established that exposure of breast tumor cells to SB-699551 elicited signaling changes in the canonical Gαi/o-coupled pathway and the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis. Moreover, conditional mutation of the HTR5A gene resulted in the loss of tumorsphere initiating cells and BTIC thus mimicking the effect of SB-699551. CONCLUSIONS: Our data provide genetic, pharmacological and phosphoproteomic evidence consistent with the on-target activity of SB-699551. The use of such agents in combination with cytotoxic chemotherapy provides a novel therapeutic approach to treat breast cancer.


Assuntos
Compostos de Bifenilo/farmacologia , Neoplasias da Mama/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Animais , Antineoplásicos/farmacologia , Compostos de Bifenilo/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Técnicas de Inativação de Genes , Guanidinas/química , Guanidinas/metabolismo , Guanidinas/farmacologia , Xenoenxertos , Humanos , Isoquinolinas/química , Isoquinolinas/metabolismo , Isoquinolinas/farmacologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Proteômica , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Serotonina/genética , Antagonistas da Serotonina/química , Antagonistas da Serotonina/metabolismo
19.
Dermatol Surg ; 46(6): 796-802, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31592915

RESUMO

BACKGROUND: Acne scarring occurs at a young age and causes distress for many patients. Various treatment modalities have been tried. OBJECTIVE: This study investigated the efficacy of combination therapy with topical poly-lactic acid and microneedle fractional radiofrequency (MFRF) for acne scars. MATERIALS AND METHODS: Patients with acne scars on both the cheeks were included. Poly-lactic acid was applied to the acne scars on one side of the face before MFRF treatment. The other side of the face was treated with MFRF and normal saline. Patients received 3 treatment sessions and were evaluated based on visual assessment and patient satisfaction. After the last treatment, objective scar assessment of scar smoothness, size, brightness, and overall improvement was performed. RESULTS: Both acne scar assessment scores and patient satisfaction were better with combination therapy (p = .036 and p = .009, respectively) than with monotherapy. Combination therapy resulted in significantly better efficacy for scar smoothness (p < .001), scar size (p = .003), and overall improvement (p < .001), but not for brightness (p = .151). CONCLUSION: Combination therapy resulted in significantly better clinical outcomes, including better scar smoothness and smaller scar size. Therefore, we believe this combination therapy is a safe and effective treatment for acne scars.


Assuntos
Acne Vulgar/complicações , Cicatriz/terapia , Preenchedores Dérmicos/administração & dosagem , Agulhamento Seco/métodos , Poliésteres/administração & dosagem , Terapia por Radiofrequência/métodos , Administração Cutânea , Adulto , Cicatriz/diagnóstico , Cicatriz/etiologia , Terapia Combinada/efeitos adversos , Terapia Combinada/instrumentação , Terapia Combinada/métodos , Agulhamento Seco/efeitos adversos , Agulhamento Seco/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Satisfação do Paciente , Terapia por Radiofrequência/efeitos adversos , Terapia por Radiofrequência/instrumentação , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
20.
Sci Rep ; 9(1): 11167, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371816

RESUMO

p16Ink4a/CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16Ink4a deficiency promotes tumor formation in various tissues. We now report that p16Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lower body weight and smaller white adipose tissue, although other major organs are unaffected. Unexpectedly, the integrity, number, and sizes of adipocytes in white adipose tissue were unaffected, as was macrophage infiltration. Hence, hypermobility appeared to be accountable for the phenotype, since food consumption was not altered. Histological analysis of the cerebellum and deep cerebellar nuclei, a vital sensorimotor control center, revealed increased proliferation of neuronal cells and improved cerebellum integrity. Expression of estrogen receptor ß (ERß) and PCNA also increased in deep cerebellar nuclei, implying crosstalk between p16Ink4a and ERß. Furthermore, p16Ink4a deficiency expands LC3B+ cells and GFAP+ astrocytes in response to estrogen. Collectively, the data suggest that loss of p16INK4a induces sexually dimorphic leanness in female mice, which appears to be due to protection against cerebellar senescence by promoting neuronal proliferation and homeostasis via ERß.


Assuntos
Cerebelo/citologia , Inibidor p16 de Quinase Dependente de Ciclina/farmacologia , Locomoção , Caracteres Sexuais , Magreza/induzido quimicamente , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Receptor Cross-Talk
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA