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1.
Artigo em Inglês | MEDLINE | ID: mdl-33531801

RESUMO

Background: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation, is a highly prevalent lung disease worldwide and imposes increasing disease burdens globally. Emphysema is one of the primary pathological features contributing to the irreversible decline of pulmonary function in COPD patients, but the pathogenetic mechanisms remain unclear. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized in the secretory pathway of living cells. Rcn3 in type II alveolar epithelial cell (AECIIs) has been reported to play a critical role in regulating perinatal lung development and bleomycin-induced lung injury-repair processes. We hypothesized that Rcn3 deficiency is associated with the development of emphysema during COPD, which is associated with the dysfunction of injury-repair modulated by alveolar epithelial cells. Materials and Methods: We examined Rcn3 expression in lung specimens from COPD patients and non-COPD control patients undergoing lung lobectomy or pneumonectomy. Two mouse models of emphysema were established by cigarette smoke (CS) exposure and intratracheal instillation of porcine pancreatic elastase (PPE). Rcn3 expression was detected in the lung tissues from these mice. Furthermore, conditional knockout (CKO) mice with Rcn3 deletion specific to AECIIs were used to explore the role of Rcn3 in PPE-induced emphysema progression. Rcn3 protein expression in lung tissues was evaluated by Western blot and immunohistochemistry. Rcn3 mRNA expression in lung tissues was detected by qPCR. Results: Rcn3 expression was significantly increased in the lung specimens from COPD patients versus non-COPD patients and the level of Rcn3 increase was associated with the degree of emphysema. Rcn3 expression were also significantly up-regulated in both CS-induced and PPE-induced emphysematous mouse lungs. Moreover, the selective ablation of Rcn3 in AECIIs significantly alleviated severity of the mouse emphysema in response to intratracheal installation of PPE. Conclusion: Our data, for the first time, indicated that suppression of Rcn3 expression in AECIIs has a beneficial effect on PPE-induced emphysema.

2.
Biochem Pharmacol ; : 114392, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33359565

RESUMO

Lung cancer remains the leading cause of cancer deaths worldwide and accounts for more than 22% of all cancer-related deaths in the US. Developing new therapies is essential to combat against deadly lung cancer, especially the most common type, non-small cell lung cancer (NSCLC). With the discovery of genome-derived functional small noncoding RNA (ncRNA), namely microRNAs (miRNA or miR), restoration of oncolytic miRNAs lost or downregulated in NSCLC cells represents a new therapeutic strategy. Very recently, we have developed a novel technology that achieves in vivo fermentation production of bioengineered miRNA agents (BERA) for research and development. In this study, we aimed at simultaneously introducing two miRNAs into NSCLC cells by using single recombinant "combinatorial BERA" (CO-BERA) molecule. Our studies show that single CO-BERA molecule (e.g., let-7c/miR-124) was successfully processed to two miRNAs (e.g., let-7c-5p and miR-124-3p) to combinatorially regulate the expression of multiple targets (e.g., RAS, VAMP3 and CDK6) in human NSCLC cells, exhibiting greater efficacy than respective BERA miRNAs in the inhibition of cell viability and colony formation. Furthermore, we demonstrate that CO-BERA let-7c/miR-124-loaded lipopolyplex nanomedicine was the most effective among tested RNAs in the control of tumor growth in NSCLC patient-derived xenograft mouse models. The anti-tumor activity of CO-BERA let-7c/miR-124 was associated with the suppression of RAS and CDK6 expression, and enhancement of apoptosis. These results support the concept to use single ncRNA agent for dual-targeting and offer insight into developing new RNA therapeutics for the treatment of lethal NSCLC.

3.
Expert Opin Biol Ther ; : 1-10, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33322950

RESUMO

Introduction: Although viruses have generally been considered as pathogens ever since their discovery, recent research has revealed that they might assume a more important role in the survival and evolution of their hosts. Besides this, they also hold the potential as therapies for the treatment of infections, cancers, and other diseases, with several of them already commercially available on the market. In this review, we will focus on the use of different viruses for treating diseases. Areas covered: This is a comprehensive review of the application of viruses or virus-based strategies (including bacteriophages, oncolytic viruses, viral vector-based delivery, virus-like particles, and virosomes) for therapeutic purposes. The article provides an overview of the status quo of currently available virus-based therapeutics. Expert Opinion: The efficacy of virus-based therapies has been emphasized repeatedly in the clinical trials for virotherapy, gene delivery, and virus-like particles (VLPs), with multiple therapeutics approved and marketed. Compared with chemical and biological drugs, viruses represent a unique 'research niche.' As more virus-based therapeutics are moving down the pipeline, we shall expect to see a more diversified collection of related products being recognized and applied in clinical settings in the future.

4.
Gland Surg ; 9(5): 1443-1449, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224819

RESUMO

Background: Breast cancer is becoming more common in young adults. The relationships between blood lipids and breast cancer have been widely studied in recent years. In our current study, we investigated the potential correlations between blood lipids and clinicopathological features of breast cancer in young females. Methods: Fifty-nine young adults (40 years or younger) with pathologically confirmed invasive breast cancer that were treated in our center from October 2015 to March 2020 were enrolled in this study. These patients were divided into the negative group (n=40, with normal blood lipids) and positive group (n=19, with abnormal blood lipids) according to the preoperative blood lipid profiles, and differences in the clinicopathological features were compared between these two groups. Results: Compared with the negative group, the positive group had a significantly higher rate of lymph node positivity (P=0.034); compared with the positive group, the negative group had a significantly higher rate of HER2 positivity (P=0.029). However, these two groups showed no significant difference in tumor size, molecular type, clinical stage, histological grade, tumor thrombus, and Ki-67 index (P values were 0.071, 0.227, 0.593, 0.396, 0.198, and 0.593, respectively). Conclusions: Blood lipid level has a certain correlation with lymph node metastasis and HER2 expression in young breast cancer patients. Therefore, blood lipid levels has a certain reference value in the clinical treatment of breast cancer.

5.
Adv Sci (Weinh) ; 7(18): 2000749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32999832

RESUMO

Silicone (Si) is one type of anode materials with intriguingly high theoretical capacity. However, the severe volume change associated with the repeated lithiation and delithiation processes hampers the mechanical/electrical integrity of Si anodes and hence reduces the battery's cycle-life. To address this issue, sequence-defined peptoids are designed and fabricated with two tailored functional groups, "-OH" and "-COOH", as cross-linkable polymeric binders for Si anodes of LIBs. Experimental results show that both the capacity and stability of such peptoids-bound Si anodes can be significantly improved due to the decreased cracks of Si nanoparticles. Particularly, the 15-mer peptoid binder in Si anode can result in a much higher reversible capacity (ca. 3110 mAh g-1) after 500 cycles at 1.0 A g-1 compared to other reported binders in literature. According to the density functional theory (DFT) calculations, it is the functional groups presented on the side chains of peptoids that facilitate the formation of Si-O binding efficiency and robustness, and then maintain the integrity of the Si anode. The sequence-designed polymers can act as a new platform for understanding the interactions between binders and Si anode materials, and promote the realization of high-performance batteries.

6.
Oncol Lett ; 20(4): 116, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32863929

RESUMO

Pectolinarigenin a plant secondary metabolite that has various biological effects, including the inhibition of melanogenesis and tumor growth. Melanoma has a high degree of malignancy, with rapid metastasis and severe drug resistance, explaining the need for new candidate drugs that inhibit tumor growth and metastasis. However, the pharmacological action and mechanism of pectolinarigenin on the growth and metastasis of melanoma remain elusive. Thus, the present study aimed to investigate the role of pectolinarigenin in melanoma cell proliferation, apoptosis, migration and invasion. Apoptotic and metastasis-associated proteins were analyzed using western blotting. The results demonstrated that pectolinarigenin treatment resulted in growth inhibition and apoptosis induction in melanoma cells, arising from the loss of mitochondrial transmembrane potential, reactive oxygen species and the altered expression of apoptosis-associated proteins. In addition, wound-healing and Transwell assays demonstrated the potential of pectolinarigenin to impair the migration and invasion of melanoma cells in accordance with the changes in the expression of the associated proteins. Therefore, the results of the present study suggested that pectolinarigenin may serve a pivotal role in promoting melanoma cell apoptosis and reducing metastasis, and may thus be a promising potential candidate for an anti-melanoma treatment strategy.

7.
J Cancer ; 11(20): 5971-5981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922538

RESUMO

Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer worldwide. Recent studies have suggested that vitamin D (VitD) is associated with a reduced risk of many chronic illnesses, including cancer. However, the role of vitamin D in OSCC has rarely been reported. Materials and Methods: The effect of vitamin D and control treatment were examined by cell clone formation assay. Using RNA-seq, we globally identified VitD-regulated long noncoding RNAs (lncRNAs). The expression of LUCAT1 in OSCC tissues and cell lines was examined by qRT-PCR. The correlation between LUCAT1 expression level and clinicopathological characteristics was analyzed. The biological roles of LUCAT1 in OSCC cell proliferation was determined by CCK8 and cell colony formation. The role of LUCAT1 in OSCC growth was further confirmed by mouse xenograft tumor model. Combined with the literature, the mechanism of action of LUICAT1 was verified by western blot. Results: In this study, we observed that VitD inhibited tumour cell growth in OSCC. We found that lncRNA LUCAT1 was downregulated by VitD and served as an important mediator of VitD in inhibiting OSCC cell proliferation. Moreover, we observed that the expression of LUCAT1 was significantly upregulated in OSCC tissues compared to non-tumour tissues. We further demonstrated that LUCAT1 promoted the proliferation of oral cancer cells by enhancing the activation of the mitogen protein kinase (MAPK) signalling pathway. Conclusion: In summary, our results show that VitD inhibited the growth of OSCC cells through the LUCAT1-MAPK signalling pathway. Our study suggested that VitD could suppress the progression of oral cancer, and LUCAT1 may be a potential tumour marker for the diagnosis and prognosis of OSCC.

8.
Bioorg Med Chem ; 28(19): 115663, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32912432

RESUMO

Pulmonary fibrosis (PF) is a disease that is characterized by abnormal epithelial-mesenchymal transition (EMT) and persistent inflammatory injury, with high mortality and poor prognosis, but the current therapies are accompanied by certain adverse side effects. In this study, we investigated the role of galangin (GA), an anti-inflammatory and anti-tumoral phytochemical extracted from galangal, in preventing and curing bleomycin (BLM)-induced pulmonary fibrosis and the underlying mechanism. Histopathological staining confirmed that GA dramatically moderated bleomycin-induced pulmonary fibrosis in mice. Compared with the vehicle treatment, GA treatment inhibited the expression of vimentin and increased the expression of E-cadherin. The expression of α-Smooth muscle actin (α-SMA), which is a myofibroblast marker, was also suppressed. In addition, GA diminished the increase in the numbers of CD4+CD69+ and CD8+CD69+ T cells and dendritic cells induced by bleomycin, and reduced the residence of inflammatory cells in the lung tissues. Notably, GA inhibited the TGF-ß1-induced EMT and fibroblast differentiation in vitro, which further confirmed the potential protective effect of GA on pulmonary fibrosis. Taken together, our results suggest that GA exerts a beneficial effect on bleomycin-induced pulmonary fibrosis by attenuating EMT and inflammatory damage and may have prevent potential of pulmonary fibrosis.

9.
Int J Clin Exp Pathol ; 13(7): 1802-1811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782708

RESUMO

OBJECTIVE: To investigate the relationship between gasdermin D (GSDMD) expression and the invasion of adenoid cystic carcinoma (ACC). METHODS: Immunohistochemistry (IHC) was used to examine GSDMD expression in tumours and adjacent non-cancerous (ANC) tissues from 33 patients with salivary ACC patients and in tumour samples from 29 patients with pleomorphic adenoma (PA). Lentiviral infection was used to stably overexpress GSDMD in ACC-LM and ACC-83 cells (GSDMD-ov cells), which were subjected to transwell and scratch tests to assess their invasive abilities compared to control cells. Cells overexpressing GSDMD were treated with siRNA targeting GSDMD, and their invasive ability was subsequently examined. RESULTS: GSDMD expression was significantly higher in ACC tissues than in corresponding ANC tissues (P<0.001). After 24 hours, both the ACC-83 and ACC-LM GSDMD-ov cell lines had more cells that moved through the membrane than did the control cells (P<0.05). For the wound healing experiment, the diameter of the wound in the GSDMD-ov cell lines was smaller than that of the control cells (P<0.001) after 24 hours. The ACC cell lines expressing high GSDMD showed stronger metastatic ability than did the control. CONCLUSION: GSDMD was highly expressed in ACC tissues compared to ANC tissues, and high GSDMD expression promoted the invasion of ACC cells. These findings suggest that GSDMD expression is related to the invasion of ACC. Our data indicate that we may be able to use GSDMD as an indicator of the invasive or metastatic potential of tumour cells in future research.

10.
ACS Nano ; 14(9): 12125-12132, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32808759

RESUMO

This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.


Assuntos
Testes Respiratórios/instrumentação , Infecções por Coronavirus/diagnóstico , Nanoestruturas , Pneumonia Viral/diagnóstico , Grupo com Ancestrais do Continente Asiático , Betacoronavirus , Biomarcadores/análise , Testes Respiratórios/métodos , China , Confiabilidade dos Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Sistema Respiratório , Sensibilidade e Especificidade
11.
Phytother Res ; 34(10): 2685-2696, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32281701

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial pneumonia that causes pulmonary tissue damage and functional impairment. To investigate the effects of cryptotanshinone on pulmonary fibrosis, the expression of NIH/3T3, HPF, and rat primary pulmonary fibroblasts was measured and found to be inhibited by CPT in a time- and concentration-dependent manner, and the upregulation of α-SMA expression in NIH/3T3 and HPF cells, which had been stimulated by TGFß-1, was decreased after CPT administration. We observed that CPT could reverse the increase in α-SMA expression and vimentin and the decrease in E-cad expression in A549 cells, which had been induced by 5 ng/mL TGFß-1, indicating that CPT has inhibitory effects in the EMT process. A BLM-induced pulmonary fibrosis model was established in C57BL/6 mice. The lung coefficient and hydroxyproline content increased significantly in the BLM-induced group and were decreased in the CPT-treated group. The expression levels of collagen-I and α-SMA and the phosphorylation level of Stat3 were significantly increased, and CPT treatment decreased these levels. Furthermore, the results from the flow cytometry analysis indicated that, in lung tissues, the frequencies of MDSCs, macrophages, DCs and T cells were considerably increased in the BLM-induced group, while CPT treatment reduced these immunocyte populations.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Bleomicina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fenantrenos/uso terapêutico , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenantrenos/farmacologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Ratos
12.
Medicine (Baltimore) ; 99(15): e19698, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282725

RESUMO

BACKGROUND: Periodontal bacteria is the major pathogens in the oral cavity and the main cause of adult chronic periodontitis, but their association with incidence and prognosis in cancer is controversial. The aim of this study was to evaluate the effect of periodontal bacteria infection on incidence and prognosis of cancer. METHODS: A systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library databases was performed to obtain 39 studies comprising 7184 participants. The incidence of cancer was evaluated as odd ratios (OR) with a 95% confidence interval (95% CI) using Review Manager 5.2 software. Overall survival, cancer-specific survival and disease-free survival, which were measured as hazard ratios (HR) with a 95% CI using Review Manager 5.2 software. RESULTS: Our results indicated that periodontal bacteria infection increased the incidence of cancer (OR = 1.25; 95%CI: 1.03-1.52) and was associated with poor overall survival (HR = 1.75; 95% CI: 1.40-2.20), disease-free survival (HR = 2.18; 95%CI: 1.24-3.84) and cancer-specific survival (HR = 1.85, 95%CI: 1.44-2.39). Subgroup analysis indicted that the risk of cancer was associated with Porphyromonas gingivalis (Pg) infection (OR = 2.16; 95%CI: 1.34-3.47) and Prevotella intermedia (Pi) infection (OR = 1.28; 95%CI: 1.01-1.63) but not Tannerella forsythia (Tf) (OR = 1.06; 95%CI: 0.8-1.41), Treponema denticola (Td) (OR = 1.30; 95%CI: 0.99-1.72), Aggregatibacter actinomycetemcomitans (Aa) (OR = 1.00; 95%CI: 0.48-2.08) and Fusobacterium nucleatum (Fn) (OR = 0.61; 95%CI: 0.32-1.16). CONCLUSION: This meta-analysis revealed periodontal bacteria infection increased the incidence of cancer and predicted poor prognosis of cancer.


Assuntos
Infecções Bacterianas/microbiologia , Periodontite Crônica/microbiologia , Boca/microbiologia , Neoplasias/epidemiologia , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Infecções Bacterianas/complicações , Periodontite Crônica/complicações , Intervalo Livre de Doença , Fusobacterium nucleatum/isolamento & purificação , Humanos , Incidência , Neoplasias/mortalidade , Porphyromonas gingivalis/isolamento & purificação , Prevotella intermedia/isolamento & purificação , Prognóstico , Medição de Risco , Treponema denticola/isolamento & purificação
13.
J Med Chem ; 63(8): 4081-4089, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32216308

RESUMO

Cationic antimicrobial peptides (CAMPs) are potent therapeutics for drug-resistant bacterial infections. However, the clinical application of CAMPs is hampered by its poor proteolytic stability and hemolytic activity toward eukaryotic cells. Great efforts have been made to design and generate derivatives of CAMPs with improved pharmacological properties. Here, we report a novel stapling protocol, which tethers two ε-amino groups of the lysine residue by the N-alkylation reaction on the hydrophilic face of amphiphilic antimicrobial peptides. A series of lysine-tethered stapled CAMPs were synthesized, employing the antimicrobial peptide OH-CM6 as a model. Biological screening of the stapled CAMPs provided an analogue with strong antimicrobial activity, high proteolytic stability, and low hemolytic activity. This novel stapling approach offers an important chemical tool for developing CAMP-based antibiotics.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Hemólise/efeitos dos fármacos , Lisina/química , Lisina/farmacologia , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Células HEK293 , Hemólise/fisiologia , Humanos , Lisina/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana/métodos
14.
15.
Nanomedicine (Lond) ; 15(5): 527-542, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32028847

RESUMO

Helicobacter pylori is a pathogen that is considered to cause several gastric disorders such as chronic gastritis, peptic ulcer and even gastric carcinoma. The current therapeutic regimens mainly constitute of a combination of several antimicrobial agents and proton pump inhibitors. However, the prevalence of antibiotic resistance has been significantly lowering the cure rates over the years. Nanocarriers possess unique strengths in this regard owing to the fact that they can protect the drugs (such as antibiotics) from the harsh environment in the stomach, penetrate the mucosal barrier and deliver drugs to the desired site. In this review we summarized recent studies of different antibacterial agents orally delivered by nanosized carriers for the eradication of H. pylori.

16.
J Oral Pathol Med ; 49(1): 30-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420988

RESUMO

BACKGROUND: Junction plakoglobin (JUP) is an important cell-cell junction protein. Recently, its deregulation has been correlated with the initiation and progression of various malignancies. Our aim was to investigate the expression of JUP in oral squamous cell carcinoma (OSCC) and its correlation with prognosis and to further study the effects of JUP on the proliferation, apoptosis, migration and invasion of OSCC cells. METHODS: We detected JUP expression in 273 OSCC specimens using immunohistochemistry. We assessed the correlation of JUP expression with clinicopathologic parameters and patient survival by Cox regression. Then, expression levels of JUP in normal oral keratinocytes (NOKs) and OSCC cell lines were detected by Western blotting and quantitative real-time PCR (qPCR). Next, we used HSC3 cells to study the effect of JUP on tumor cell proliferation, apoptosis, migration, and invasion by using cell counting kit-8, flow cytometry, and transwell assays, respectively. RESULTS: Cox regression showed that high expression of JUP was related to the poor prognosis of OSCC patients. Western blotting and qPCR assays showed that the expression level of JUP in OSCC cell lines was higher than that in NOKs. Overexpression of JUP promoted the proliferation, metastasis, and invasion of HSC3 cells and inhibited apoptosis, while the opposite was observed after JUP knockdown. CONCLUSION: This study initially revealed that JUP was overexpressed in OSCC, and that JUP promoted the proliferation, migration, and invasion of OSCC cells and inhibited apoptosis. Moreover, high expression of JUP could be used as a potential prognostic marker of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , gama Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Prognóstico
17.
J Drug Target ; 28(3): 271-281, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31613147

RESUMO

Antimicrobial lipids have been recognised as broad-spectrum antibacterial agents. They can directly act on and lyse bacterial cell membrane, and inhibit bacterial growth through a range of mechanisms. Antimicrobial lipids include free fatty acids, monoglycerides, cholesteryl ester, sphingolipids and etc., with the first two being the most extensively studied. Their application is usually hindered by the low solubility of the compounds themselves, and nano-sized lipid-based carriers can endow druggability to these antimicrobial agents for they improve lipid solubility and dispersion in aqueous formulations. Nano-carriers also possess advantages in overcoming drug resistance. In this review we will discuss different kinds of antimicrobial lipids in nano-sized carriers for antibacterial delivery. CAL02 as a promising infection-controlling liposome consisted of cholesterol and sphingomyelin will also be included for it's a unique anti-infection approach, which signifies that the underlying antibacterial roles antimicrobial lipids needs to be further addressed. With the global emergence of antibiotic resistance, antimicrobial lipids formulated in nano-carriers might provide a novel alternative in combatting infectious diseases.

18.
Int J Biol Macromol ; 153: 1291-1298, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759011

RESUMO

The aim of this work was to develop new, rice starch-based superabsorbent materials (SPAMs), degradable and eco-friendly. Indica rice starch-based SPAM had the best water absorption capacity (439 g water/g) with a relatively high amylose content (23.6%) that may enhance the interaction and structural strength of polymer chains through the formation of hydrogen-bond. Meanwhile, the rigidity and structure of branched chain of amylopectin can improve the water holding capacity, thus the glutinous rice starch (75.1% amylopectin content)-based SPAM also had good water absorption characteristics (399 g water/g). Regeneration rate has a certain correlation with water absorption rate, therefore, the indica rice starch-based SPAMs only lost 30% of their reswelling capacity when reused three consecutive times. On the other hand, the effects of 4 cations on SPAM water absorption were according the following order: K+ < Na+ < Ca2+ < Al3+. The formation of graft copolymer of sodium acrylate and rice starch was confirmed by Fourier Transform Infra-Red spectroscopy and X-Ray diffraction. The microstructure of SPAM showed a porous arrangement as observed by scanning electron microscopy. Finally, when present within the storage environment, the indica rice starch-based SPAM was effective in preventing rice grain moisture accumulation.

19.
Acta Biomater ; 103: 259-271, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31846803

RESUMO

Multidrug resistance of cancer cells is one of the major obstacle for chemotherapeutic efficiency. Nitric oxide (NO) has raised the potential to overcome multidrug resistance (MDR) with low side effects. Herein, we report a reactive oxygen species (ROS) and glutathione (GSH) responsive nanoparticle for the delivery of NO prodrug such as S-nitrosoglutathione (GSNO), which was chemically conjugated to an amphiphilic block copolymer. The GSNO functionalized nanoparticles show high NO loading capacity, good stability and sustained NO release with specific GSH activated NO-releasing kinetics. Such GSNO functionalized nanoparticles delivered doxorubicin (DOX) in a ROS triggered manner and increased the intracellular accumulation of DOX. However, in normal healthy cells, showing physiological concentrations of ROS, these nanoparticles presented good biocompatibility. The present work indicated that these multifunctional nanoparticles can serve as effective co-delivery platforms of NO and DOX to selectively kill chemo-resistant cancer cells through increasing chemo-sensitivity. STATEMENT OF SIGNIFICANCE: In this work, we constructed nitric oxide donor (S-nitrosoglutathione, GSNO) functionalized amphiphilic copolymer (PEG-PPS-GSNO) to deliver doxorubicin (DOX). The developed PEG-PPS-GSNO@DOX nanoparticles presented high NO capacity, ROS triggered DOX release and GSH triggered NO release. Thus NO reversed the chemo-resistance in HepG2/ADR cells increasing intrcellular accumulation of DOX. Furthermore, these PEG-PPS-GSNO@DOX nanoparticles exhibited biocompatibility to healthy cells and toxicity to cancer cells, due to elevated ROS.

20.
Cell Death Dis ; 10(12): 936, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819048

RESUMO

Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/dietoterapia , Cisplatino/farmacologia , Suplementos Nutricionais , Lipocalina-2/metabolismo , Neoplasias Bucais/dietoterapia , NF-kappa B/metabolismo , Proteínas Ribossômicas/metabolismo , Vitamina D/uso terapêutico , Adulto , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Lipocalina-2/antagonistas & inibidores , Lipocalina-2/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Receptores de Calcitriol/genética , Proteínas Ribossômicas/genética , Transdução de Sinais/efeitos dos fármacos , Transfecção , Carga Tumoral/efeitos dos fármacos , Vitamina D/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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