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1.
Neoplasia ; 36: 100863, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36528911

RESUMO

Gastric cancer is one of most lethal diseases across the world. However, the underlying mechanism of gastric cancer carcinogenesis and development is still not fully known. Forkhead box M1 (FOXM1) belongs to the FOX family and has crucial roles in transactivation of multiple oncogenes in several cancer types, including gastric cancer. Recent studies have also shown the non-transcriptional function of FOXM1 via protein-protein interactions. Human telomerase reverse transcriptase (hTERT) is the core subunit of telomerase that facilitates cancer initiation and progression by maintaining cell immortalization, promoting cell proliferation and inhibiting cell apoptosis. However, the relationship between FOXM1 and hTERT in gastric cancer is still unclear. In our study, we found that FOXM1 and hTERT were convergent to the cell cycle-related pathways and they were positively related with advanced gastric cancer stages and poor outcomes. Simultaneous high levels of FOXM1 and hTERT predicted the worst prognosis. FOXM1 could increase hTERT protein rather than mRNA levels in a non-transcriptional manner. Mechanistically, FOXM1 interrupted the interaction between the E3 ligase MKRN1 and hTERT and decreased hTERT protein degradation. Further studies revealed that FOXM1 interacted with hTERT through its DNA-binding domain (DBD) region. Finally, we found that hTERT played important roles in FOXM1-mediated activation of the Wnt/ß-catenin pathway to promote gastric cancer cell proliferation. Taken together, we found a novel non-classical function of FOXM1 to increase hTERT protein stability. Targeting the FOXM1-hTERT pathway may be a potential therapeutic strategy in treating gastric cancer.


Assuntos
Neoplasias Gástricas , Telomerase , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Prognóstico , Estabilidade Proteica , Neoplasias Gástricas/metabolismo , Telomerase/genética , Telomerase/metabolismo
2.
ACS Appl Mater Interfaces ; 15(1): 249-264, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36548196

RESUMO

The regenerative repair of segmental bone defect (SBD) is an urgent problem in the field of orthopedics. Rapid induction of angiogenesis and osteoinductivity after implantation of scaffold is critical. In this study, a unique tissue engineering strategy with mixture of peripheral blood-derived mesenchymal stem cells (PBMSC) and endothelial progenitor cells (PBEPC) was applied in a 3D-printed biphasic calcium phosphate (BCP) scaffold with highly bioactive nano hydroxyapatite (nHA) coating (nHA/BCP) to construct a novel vascularized tissue engineered bone (VTEB) for rabbit femoral SBD repair. The 2D coculture of PBMSC and PBEPC showed that they could promote the osteogenic or angiogenic differentiation of the cells from each other, especially in the group of PBEPC/PBMSC = 75:25. Besides, the 3D coculture results exhibited that the nHA coating could further promote PBEPC/PBMSC adhesion, proliferation, and osteogenic and angiogenic differentiation on the BCP scaffold. In vivo experiments showed that among the four groups (BCP, BCP-PBEPC/PBMSC, nHA/BCP, and nHA/BCP-PBEPC/PBMSC), the nHA/BCP-PBEPC/PBMSC group induced the best formation of blood vessels and new bone and, thus, the good repair of SBD. It revealed the synergistic effect of nHA and PBEPC/PBMSC on the angiogenesis and osteogenesis of the BCP scaffold. Therefore, the construction of VTEB in this study could provide a possibility for the regenerative repair of SBD.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Animais , Coelhos , Engenharia Tecidual/métodos , Hidroxiapatitas/farmacologia , Durapatita/farmacologia , Osteogênese , Diferenciação Celular , Regeneração Óssea
3.
Oncol Lett ; 24(6): 444, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36420077

RESUMO

In tumor research, the occurrence and origin of tumors are the fundamental problems. In the 1970s, the basic discussion of the developmental biology problem of tumors was proposed, and it was believed that tumorigenesis is closely related to developmental biology. Tumors are abnormal biological structures in organisms, and their biological behavior is very similar to that of the early embryo. Many tumor-related genes also serve regulatory roles in the normal development and differentiation of embryos. However, it remains unclear whether gene expression in early embryos has any similarities with tumor cells. In this study, to compare the similarities and differences in gene expression between early embryos and tumor cells, reverse transcription-quantitative PCR was conducted to determine and compare the relative expression levels of nine tumor-related genes in the brain glioma cell line, T98G, and in the early embryo of Spodoptera litura, which is fast-growing, low-cost, easily accessible and easy to observe. The expression of tumor-related genes in early embryos and the similarity of regulatory mechanisms between early embryonic development and tumor growth were explored. In conclusion, tumor growth may be regarded as an abnormal embryogenic activation that happens in the organs of adult individuals.

4.
Inflamm Res ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329130

RESUMO

BACKGROUND: Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL). OBJECTIVE: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment. METHODS: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 µM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR. RESULTS: Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions. CONCLUSION: The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions.

5.
Skin Res Technol ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36426837

RESUMO

BACKGROUND: Facial erythema, a prominent characteristic of rosacea, causes concern to both the patient and doctor. In clinical practice, commonly used erythema severity subjective assessment tools lack objectivity and are less comprehensive. Even with images taken by the VISIA® system, diffused erythema is difficult to segment and evaluate fully due to the automatic threshold segmentation method. This study aimed to explore a more objective and scientific erythema quantification tool with the aid of the ImageJ software analysis of the red area images taken by the VISIA® system. MATERIALS AND METHODS: Patients with rosacea were enrolled and assessed for the clinical severity of their illness using various stools-the standard grading systems (SGS) for rosacea, investigator's global assessment (IGA), and clinician's erythema assessment (CEA). Facial images in the red area mode of the VISIA® system were further analyzed by the ImageJ for the relative intensity of redness and percentage of erythema area; the correlation with the scores of the subjective grading systems was evaluated. RESULTS: This study included 201 patients (195 females and 6 males). The relative intensity of redness was positively correlated to the SGS, IGA, and CEA scores (0.688, 0.725, and 0.718, respectively) (p < 0.001). The percentage of erythema area was positively correlated to the SGS, IGA, and CEA scores (0.615, 0.666, and 0.656, respectively) (p < 0.001). CONCLUSION: We demonstrated a more objective and precise method of assessing the severity of facial erythema rosacea, which could comprehensively assess the severity by both the area and intensity of facial erythema.

6.
Front Microbiol ; 13: 972777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992650

RESUMO

Considered as the most popular pathogen worldwide, Helicobacter pylori is intensively associated with diverse gastric diseases, including gastric ulcers, chronic progressive gastritis, and gastric cancer. Aside from its pathogenic effect on gastric diseases, growing evidences reveal that H. pylori may be related to numerous extragastric diseases. In this article, we reviewed recent studies and systematically elucidated that H. pylori may interfere with many biological processes outside the stomach and influence the occurrence of various extragastric diseases. Many epidemiological studies have indicated that H. pylori plays a pathogenic role in COVID-19, atherosclerosis, hyperemesis gravidarum and several other extragastric diseases, while the effect of H. pylori is currently under investigation in gastroesophageal reflux disease, asthma, and inflammatory bowel disease. Moreover, we also summarized the possible pathogenic mechanisms of H. pylori that may be related to chronic systemic inflammation and molecular mimicker. Taken together, this review provides a new perspective on the role of H. pylori in extragastric diseases and explores the possible mechanisms, which may help guide clinical treatment.

7.
J Diabetes ; 14(8): 551-561, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36040201

RESUMO

BACKGROUND: We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN). METHODS: Patients with PDN (n = 68) were included in a single-center, randomized, single-blind, double-dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN). Secondary outcomes evaluated included the reduction of BPI-DPN >50%, changes in the numeric rating scale-11 (NRS-11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events. RESULTS: After 10 weeks of treatment, the BPI-DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (Ps < 0.001), respectively. The difference in the absolute change in BPI-DPN score between both groups was -1.79 (95% CI: -9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI-DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS-11 and DSID (Ps > 0.05). A significantly greater number of patients in the XF group felt "significantly improved" or "improved" than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group -2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group. CONCLUSIONS: XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Analgésicos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Método Duplo-Cego , Humanos , NAD/uso terapêutico , Dor , Medição da Dor , Pregabalina/uso terapêutico , Qualidade de Vida , Método Simples-Cego , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêutico
8.
Skin Res Technol ; 28(5): 708-713, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35644027

RESUMO

BACKGROUND: The neural basis of rosacea is not well understood. This study aimed to determine whether cerebral glucose metabolism (CGM) changes on 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/computed tomography (CT) scans can detect functional network changes in specific brain areas in patients with rosacea. MATERIALS AND METHODS: Eight adults with rosacea and 10 age/sex-matched healthy adults (controls) were enrolled in the study. 18 F-FDG PET/CT brain images for all eight patients and whole-body images for two of the patients were analyzed qualitatively and semi-quantitatively. Differences between the study groups were examined using Fischer's exact test and a Student's t-test. A voxel-based analysis using statistical parametric mapping was performed to compare the brain metabolism of the patients with that of the controls. RESULTS: Compared with the controls, the patients with rosacea showed extensive changes in the CGM signals in the cerebral cortex and limbic system, with less CGM shown in the right superior parietal lobule, right postcentral gyrus, right parahippocampal gyrus, left superior frontal gyrus, and lateral posterior thalamic nucleus and more CGM in the right precentral gyrus, left inferior frontal gyrus, and cerebellar tonsil. No dysmetabolic lesions were found in the whole-body 18 F-FDG PET/CT images. CONCLUSION: Specific neural functional changes occur in patients with rosacea that may explain its pathogenesis.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rosácea , Adulto , Estudos Transversais , Fluordesoxiglucose F18 , Glucose , Humanos , Rosácea/diagnóstico por imagem
11.
Bioact Mater ; 12: 278-291, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35310383

RESUMO

Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness, high recurrence, and poor prognosis. Currently, surgical resection is the main treatment for fibrosarcoma. However, due to the lack of specific biomarkers, the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival. Here, we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells (HT1080) but not human embryonic lung fibroblast cells with Kd values in the nanomolar range. In addition, we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients. Furthermore, we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria. Moreover, we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration. Finally, we investigated the biologically functional cellular target of S11e using a mass spectrometry approach, and identified that Diablo/SMAC protein is a cellular binding protein of S11e, by interacting to which S11e inhibited HT1080 cell migration and invasion. Taken together, these results provide the evidence that S11e may be useful for early diagnosis, targeted therapy, and prognostication of fibrosarcoma.

12.
Sci Rep ; 12(1): 4545, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296801

RESUMO

The zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH3)3C]2Sal}22-) is a zinc ion chelate of salicylate. In this study, we found that this compound inhibits viability, invasion, and migration and induces apoptosis in triple-negative breast cancer 4T1 cells. RNA-seq showed that the expression of 17 genes was upregulated and 26 genes were downregulated significantly by Zn{[CH3)3C]2Sal}22- treatment. Further GO and KEGG analysis showed that the activity of Zn{[CH3)3C]2Sal}22- against triple-negative breast cancer cells may be involved in the JAK-STAT3, HIF-1, and TNF signaling pathways. The expression of key genes was verified by RT-PCR. The phosphorylation of STAT3 and its upstream SRC decreased drastically upon Zn{[CH3)3C]2Sal}22- treatment, as demonstrated by western blot. Our results indicate that Zn{[CH3)3C]2Sal}22- inhibits the activity of TNBC cells by downregulating the STAT3 signaling through the SRC pathway.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Humanos , Salicilatos/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Zinco/farmacologia
13.
Med Res Rev ; 42(3): 1037-1063, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34786735

RESUMO

Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that can both self-renew and differentiate into other cell types forming the heterogeneous tumor bulk. Since CSCs are involved in all aspects of cancer development, including tumor initiation, cell proliferation, metastatic dissemination, therapy resistance, and recurrence, they have emerged as attractive targets for cancer treatment and management. Salinomycin, a widely used antibiotic in poultry farming, was identified by the Weinberg group as a potent anti-CSC agent in 2009. As a polyether ionophore, salinomycin exerts broad-spectrum activities, including the important anti-CSC function. Studies on the mechanism of action of salinomycin against cancer have been continuously and rapidly published since then. Thus, it is imperative for us to update its literature of recent research findings in this area. We here summarize the notable work reported on salinomycin's anticancer activities, intracellular binding target(s), effects on tumor microenvironment, safety, derivatives, and tumor-specific drug delivery; after that we also discuss the translational potential of salinomycin toward clinical application based on current multifaceted understandings.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Piranos/metabolismo , Piranos/farmacologia , Piranos/uso terapêutico , Microambiente Tumoral
14.
Front Immunol ; 12: 609615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322115

RESUMO

Background: Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration. Objective: To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment. Methods: Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1ß) evaluation. An in vivo murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical facial images of patients were obtained using the VISIA skin analysis system before, 4, and 6 months following oral carvedilol administration. Results: Rosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-α, and IL-1ß). In vivo, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. In vitro, carvedilol decreased TLR2 expression in RAW 264.7 cells, further reducing KLK5 secretion and LL-37 expression and ultimately inhibiting rosacea-like inflammatory reactions. Clinical manifestations and facial redness obviously improved during 6-month follow-up with systemic carvedilol administration. Conclusion: Carvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism.


Assuntos
Anti-Inflamatórios/uso terapêutico , Carvedilol/uso terapêutico , Macrófagos/efeitos dos fármacos , Rosácea/tratamento farmacológico , Pele/efeitos dos fármacos , Receptor 2 Toll-Like/antagonistas & inibidores , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Calicreínas/genética , Calicreínas/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Rosácea/imunologia , Rosácea/metabolismo , Rosácea/patologia , Pele/imunologia , Pele/metabolismo , Pele/patologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Resultado do Tratamento , Catelicidinas
15.
Front Oncol ; 11: 619346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796457

RESUMO

The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases.

16.
Medicine (Baltimore) ; 100(3): e23986, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545988

RESUMO

ABSTRACT: Rosacea is a facial chronic inflammatory skin disease with immune and vascular system dysfunction. Paeoniflorin (PF) is a traditional Chinese medicine with anti-inflammatory properties. However, its effects on rosacea remain unknown. Here, we investigated the mechanisms through which PF inhibits the macrophage-related rosacea-like inflammatory response. Immunohistochemical methods were used to detect differences in the inflammatory response and degree of macrophage infiltration in granulomatous rosacea lesions and their peripheral areas. Cell Counting Kit-8 was used to determine the cytotoxicity of PF towards RAW 264.7 cells. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure the influence of PF on mRNA and protein expression levels of suppressor of cytokine signaling 3 (SOCS3), apoptosis signal-regulating kinase 1 (ASK1)-p38, Toll-like receptor 2, and cathelicidin antimicrobial peptide ( or LL37) in the lipopolysaccharide (LPS)-induced macrophage-related rosacea-like inflammatory response of RAW 264.7 cells. Inflammatory cell infiltration was more pronounced in granulomatous rosacea lesions than in peripheral areas. LL37 expression increased significantly, and the infiltration of a large number of CD68+ macrophages was observed in the lesions. PF promoted SOCS3 expression in RAW 264.7 cells and inhibited the LPS-induced increase in toll-like receptor 2 and LL37 expression through the ASK1-p38 cascade, thereby alleviating the macrophage-related rosacea-like inflammatory response. These changes could be abrogated by SOCS3 siRNA in vitro.In conclusion, the pathogenesis of rosacea involves abnormal macrophage infiltration within the lesions. PF inhibits the macrophage-related rosacea-like inflammatory response through the SOCS3-ASK1-p38 pathway, demonstrating its potential application as a novel drug for rosacea therapy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Glucosídeos/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Monoterpenos/farmacologia , Rosácea/tratamento farmacológico , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Técnicas de Cultura de Células , Humanos , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Pele/citologia
17.
Curr Med Chem ; 28(31): 6307-6322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32503398

RESUMO

Nanoparticles are widely used in cancer therapy because of their nanoscale, high surface ratio, multifunctionality and so on. With specific construction of nanoparticles, by choosing magnetic nanomaterials or citric acid-coated nanoparticle, scientists can kill tumor cells effectively and accurately, importantly reducing the side effects of conventional chemotherapy. Scientists not only have designed nanoparticles loaded with therapeutic drugs, but also those equipped with targeted molecules. These works have made nanoparticles multifunctional nanocarriers. As multifunctional nanocarriers, nanoparticles play an important role of drug delivery and normally, enabling drug delivery to tumor tissues is a difficult task. During the period of internal circulation, it is hard to maintain the stability of the nanocarriers not attached to normal cells or serum. With the application of stimulus-responsive nanomaterials, scientists have developed many nanocarriers with controllable drug release. These controllable drug delivery systems can quickly respond to microenvironmental changes (PH, enzyme, etc.) or external stimuli (photo, heat, magnetic or electric fields). Thus, to overcome the side effects of controllable drug delivery systems in vivo, in this article, we summarize the various kinds of stimulus-responsive nanocarriers for cancer therapy and discuss the possibilities and challenges in future application.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nanopartículas , Neoplasias , Preparações de Ação Retardada , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Neoplasias/tratamento farmacológico
18.
J Cosmet Dermatol ; 20(9): 2715-2722, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33350031

RESUMO

BACKGROUND: Rosacea and cardiovascular diseases (CVD) are chronic inflammatory disorders. While CVD is the leading cause of mortality globally, increasing evidence indicates that CVD prevalence could be higher among patients with rosacea. AIMS: This review aimed to determine the association between the prevalence of CVD and rosacea. PATIENTS/METHODS: A systematic review of observational studies with controls available in MEDLINE, EMBASE, PubMed, Cochrane, and Web of Science databases was conducted. We performed a pooled meta-analysis using random-effects weighting. Overall, 11 studies met the inclusion criteria, which indicated increased odds for at least one risk factor of CVD, including diabetes, high blood pressure, or dyslipidemia. RESULTS: The pooled meta-analysis indicated an association of rosacea with higher odds of insulin resistance or diabetes (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.97-1.45), high systolic blood pressure (OR, 1.96; 95% CI, 1.35-2.84), dyslipidemia (OR, 1.50; 95% CI, 1.19-1.88), and CVD (OR, 6.65; 95% CI, 2.80-15.76). No publication bias was detected. The effect of confounding factors due to overlapping symptoms and lack of individual-level data were limitations of this review. CONCLUSION: Patients with rosacea have a high risk of CVD. However, further studies are warranted to confirm the association between rosacea and CVD.


Assuntos
Doenças Cardiovasculares , Rosácea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Prevalência , Fatores de Risco , Rosácea/epidemiologia
20.
Plants (Basel) ; 9(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365552

RESUMO

Rehmannia glutinosa production is affected by replanting disease, in which autotoxic harm to plants is mediated by endogenous phenolic acids as allelopathic compounds found in root exudates. These phenolic acids are mostly phenylpropanoid products of plants' secondary metabolisms. The molecular mechanism of their biosynthesis and release has not been explored in R. glutinosa. P-coumarate-3-hydroxylase (C3H) is the second hydroxylase gene involved in the phenolic acid/phenylpropanoid biosynthesis pathways. C3Hs have been functionally characterized in several plants. However, limited information is available on the C3H gene in R. glutinosa. Here, we identified a putative RgC3H gene and predicted its potential function by in silico analysis and subcellular localization. Overexpression or repression of RgC3H in the transgenic R. glutinosa roots indicated that the gene was involved in allelopathic phenolic biosynthesis. Moreover, we found that these phenolic acid release amount of the transgenic R. glutinosa roots were altered, implying that RgC3H positively promotes their release via the molecular networks of the activated phenolic acid/phenylpropanoid pathways. This study revealed that RgC3H plays roles in the biosynthesis and release of allelopathic phenolic acids in R. glutinosa roots, laying a basis for further clarifying the molecular mechanism of the replanting disease development.

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