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2.
Front Pharmacol ; 12: 775506, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776986

RESUMO

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34774435

RESUMO

The rare earth materials have attracted intensive attention due to their strong luminescent characteristic. However, the split fine Stark levels are difficult to be determined. Here we report a room-temperature detection for Stark levels of YNbO4: Er3+ using established laser-induced spectroscopy system with dye laser of superhigh resolution of wavelength at 0.005 nm. From excitation spectra, six split Stark levels of 4G11/2 (Er3+) were directly detected. Moreover, nonradiative relaxations of 4G9/2→4G11/2 and 4G11/2→2H11/2/ 4S3/2 have been observed with weighed lifetimes of 0.70 µs and 6.15 µs, and characteristic green emission of Er3+ (@555 nm) yields lifetime of 31.78 µs.

4.
Curr Top Med Chem ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34607544

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti-MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

5.
Dermatol Surg ; 47(12): 1665-1666, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34608080
6.
Mol Biol Rep ; 48(12): 7743-7753, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34689294

RESUMO

BACKGROUND: More than half of Neuroblastoma (NB) patients presented with distant metastases and the relapse of metastatic patients was up to 90%. It is urgent to explore a biomarker that could facilitate the prediction of metastasis in NB patients. METHODS AND RESULTS: In the present study, we systematically analyzed Gene Expression Omnibus datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NB metastasis. In total, 176 up-regulated and 19 down-regulated differentially expressed genes (DEGs) were identified. Based on these DEGs, a PPI network composed of 150 nodes and 452 interactions was established. Through PPI network identification combined with qRT-PCR, ELISA and IHC, S100A9 was screened as an outstanding gene. Furthermore, in vitro tumorigenesis assays demonstrated that S100A9 overexpression enhanced the proliferation, migration and invasion of NB cells. CONCLUSIONS: Taken together, our findings suggested that S100A9 could participate in NB tumorigenesis and progression. In addition, S100A9 has the potential to be used as a promising clinical biomarker in the prediction of NB metastasis.

7.
Lab Chip ; 21(22): 4414-4426, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34676383

RESUMO

Among the numerous forms of cancer immunotherapy, cancer vaccines have attracted increasing attention because of their ability to elicit sustained antitumor immune responses and durable tumor regression. Here, a personalized gel-droplet monocyte vaccine (GEMA) derived from host blood was reported. A streamlined microfluidic vaccine production platform was designed to combine the separation of monocytes from host blood and the encapsulation of monocytes in an alginate gel droplet, which simplified the handling of the blood product and permitted the rapid preparation of vaccines. In addition, the application of alginate gel encapsulation not only improved the efficiency of antigen uptake by monocytes, but it also promoted the production of antigen-specific CD8+ T cells in the spleen, resulting in an intense cytotoxic T lymphocyte (CTL) response. Moreover, depending on the disease profile of a specific patient, different adjuvant- and antigen-loaded monocytes could be simultaneously encapsulated in gel droplets to prepare a cocktail vaccine based on patient needs. In this study, anti-PD-1 antibodies were encapsulated in gel droplets as a model adjuvant to obtain a cocktail vaccine, and this demonstrated enhanced antitumor efficacy in a 4T1 breast tumor model. In summary, this study provided a unique vaccine production strategy and an efficient combination therapy approach, holding great promise for the development of personalized cancer vaccines.


Assuntos
Neoplasias da Mama , Vacinas Anticâncer , Linfócitos T CD8-Positivos , Células Dendríticas , Feminino , Humanos , Imunoterapia , Monócitos
8.
J Hazard Mater ; 416: 126146, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492932

RESUMO

As worldwide edible fungi, Lentinula edodes and Agaricus bisporus accumulate both essential and harmful metals. Metal bioavailability is important for metal benefit-risk assessment. A full functional model of digestive tracts (including digestion, metabolism, and absorption) is established. Under the digestive tract functions, the bioaccessible and bioavailable metals are released from edible fungi and absorbed by intestinal tract, respectively. Based on bioavailable metal contents in the intestine, safe dosage and maximum consumption are 43.52 g/d and 248.7 g/d for Agaricus bisporu, 20.59/328.9 g/d (for males/ female) and 132.9 g/d for Lentinus edodes; V, Co, Ni, Cu, Zn, Se, Cr, Cd and Pb in Agaricus bisporus and Lentinula edodes are absorbed mainly in the large intestine; Fe is mainly absorbed in small intestine; edible fungi species-specificity in metal bioavailability is observed for As and Mn, which are mainly absorbed by small and large intestine for Agaricus bisporus and Lentinus edodes, respectively; and then metal toxicity on small and large intestine is disclosed. Metal benefit-risk is assessed by the content of monolayer liposome-extracted metal in the chyme from small and large intestine, which is controlled by the gastrointestinal functions, metal and edible fungi species.


Assuntos
Agaricus , Metais Pesados , Disponibilidade Biológica , Biomimética , Digestão , Monitoramento Ambiental , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Metais Pesados/análise , Medição de Risco
9.
Genes Dis ; 8(6): 781-797, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522708

RESUMO

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer, which can be mediated through the stimulation of chronic inflammation. In effect, the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer. In other words, chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer. Here, we provide a detailed and comprehensive account of the link between chronic inflammation, the microbiome and bladder cancer. Finally, we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.

10.
Nanomaterials (Basel) ; 11(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34578669

RESUMO

Martensite transformation and grain refinement can make austenitic stainless steel stronger, but this comes at a dramatic loss of both ductility and corrosion resistance. Here we report a novel gradient structure in 301 stainless steel sheets, which enables an unprecedented combination of high strength, improved ductility and good corrosion resistance. After producing inter-layer microstructure gradient by surface mechanical attrition treatment, the sheet was annealed at high temperature for a short duration, during which partial reverse transformation occurred to form recrystallized austenitic nano-grains in the surface layer, i.e., introducing extra intra-layer heterogeneity. Such 3D microstructure heterogeneity activates inter-layer and inter-phase interactions during deformation, thereby producing back stress for high yield strength and hetero-deformation induced (HDI) hardening for high ductility. Importantly, the recrystallized austenitic nano-grains significantly ameliorates the corrosion resistance. These findings suggest an effective route for evading the strength-ductility and strength-corrosion tradeoffs in stainless steels simultaneously.

11.
Environ Manage ; 68(6): 928-936, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34529125

RESUMO

The health of the lower basin of the Volta River in Ghana was evaluated in January-February and May-June 2016 using physicochemical parameters and benthic macroinvertebrates sampled at 10 locations. Selected environmental variables were compared to accepted environmental water quality standard values where applicable. Principal component analysis (PCA) and redundancy analysis (RDA) were used to analyse the association between the benthic macroinvertebrates distribution and physicochemical variables. Pesticide concentrations were generally below the limit of detection 0.01 and 0.005 µg/L for organophosphate/synthetic pyrethroid and organochlorines respectively. Nutrient levels were also generally low; however, significant differences existed between the values of physicochemical parameters at the different sampling sites and seasons (Monte Carlo permutation test; p = 0.002), as well as between the abundance of macroinvertebrates at the different sites and seasons (p = 0.002). The environmental variables dissolved oxygen (DO), phosphate, pH, substratum (p < 0.05), turbidity, conductivity, total dissolved solids, total solids and nitrate (0.05 < p < 0.10) significantly explained the variation in macroinvertebrate composition between sampling stations in the Volta River. Polypedilum fuscipenne, was positively correlated with turbidity and DO concentrations; Physa sp., Centroptilum sp., Centroptiloides sp., Phaon iridipennis and juvenile fish were positively correlated with nitrate concentration and pH and negatively correlated with turbidity and DO. Polluted sites were dominated by the snail Lymnaea glabra. This demonstrates that physicochemical parameters and macroinvertebrates could be applied to describe the water quality and improve the biomonitoring for water resources management and the environmental protection in the Lower Volta River.

12.
Eur J Pharmacol ; 911: 174482, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34481875

RESUMO

Berberine facilitates the production of glucagon-like peptide-1 (GLP-1) by intestinal L cells. Here, we aimed to reveal the mechanism of berberine facilitating the production of GLP-1 by intestinal L cells. In this study, we confirmed that the 100 mg/kg berberine daily through diet decreased the miR-106b expression and elevated the expressions of ß-catenin and T-cell factor 4 (TCF4) in colon tissues of high-fat diet mice; berberine decreased the concentrations of triglycerides, total cholesterol and the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in mouse serum samples; berberine decreased the blood glucose in the mouse tail vein blood and promoted GLP-1 production by intestinal L cells in mouse serum samples and elevated the GLP-1 expression in mouse colon tissues. Meanwhile, the mechanism analysis demonstrated that a dose of 100 µM berberine down-regulated the miR-106b expression by elevating the methylation levels of miR-106b in STC-1 cells and miR-106b bound to TCF4 in 293T cells. Moreover, the 100 mg/kg berberine daily through diet activated the ß-catenin/TCF4 signaling pathway by decreasing miR-106b, thereby facilitating GLP-1 production in intestinal L cells through the in vivo assays. Conclusively, our experimental data illustrated that berberine decreased miR-106b expression by increasing its methylation levels and then activated the ß-catenin/TCF4 signaling pathway, thereby facilitating GLP-1 production by intestinal L cells.

13.
Vaccine ; 39(37): 5285-5294, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34373122

RESUMO

Vaccination is the most economic and effective measure to deal with infectious diseases and protect public health. Nowadays, due to the spread of COVID-19 and the ensuing pandemic, safe, effective vaccines are in urgent need. However, due to concerns about vaccine safety, there is still reluctance to vaccinate. In China, in response to the Changchun Changsheng Vaccine incident, the National People's Congress Standing Committee passed the Vaccine Administration Law in 2019, which marks China's first comprehensive piece of legislation on vaccine regulation. The law establishes a regulatory system covering the entire life cycle of vaccines, introduces the vaccine marketing authorization holder system, stipulates the legal responsibilities of all parties, and further clarifies the compensation system for any individuals who exhibit abnormal reactions to vaccination. In addition, it emphasizes the use of modern technology to build a national vaccine electronic platform for tracing. To balance vaccine efficacy and safety, it is necessary to further improve the vaccine risk management mechanism, promote cooperation between government and non-governmental actors, and avoid improper interventions in the vaccine market.


Assuntos
COVID-19 , Vacinas , China , Humanos , SARS-CoV-2 , Vacinação , Vacinas/efeitos adversos
14.
Clin Chim Acta ; 522: 23-30, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34389280

RESUMO

Nesfatin-1, an anorexic neuropeptide discovered in 2006, is widely distributed in the central nervous system and peripheral tissues. It has been shown to be involved in the regulation of food intake and lipid metabolism, inhibiting fat accumulation, accelerating lipid decomposition, and in general, inhibiting the development of lipid-related diseases, such as obesity and metabolic syndrome. Potential mechanisms of Nesfatin-1 action in lipid metabolism and lipid-related diseases will be discussed as well as its role as a biomarker in cardiovascular disease. This review expected to provide a new strategy for the diagnosis and prevention of clinically related diseases.


Assuntos
Proteínas de Ligação ao Cálcio , Metabolismo dos Lipídeos , Proteínas de Ligação a DNA , Humanos , Lipídeos , Proteínas do Tecido Nervoso , Nucleobindinas
16.
J Exp Clin Cancer Res ; 40(1): 250, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372912

RESUMO

Primary liver cancer (PLC) is a common malignancy with high morbidity and mortality. Poor prognosis and easy recurrence on PLC patients calls for optimizations of the current conventional treatments and the exploration of novel therapeutic strategies. For most malignancies, including PLC, immune cells play crucial roles in regulating tumor microenvironments and specifically recognizing tumor cells. Therefore, cellular based immunotherapy has its instinctive advantages in PLC therapy as a novel therapeutic strategy. From the active and passive immune perspectives, we introduced the cellular based immunotherapies for PLC in this review, covering both the lymphoid and myeloid cells. Then we briefly review the combined cellular immunotherapeutic approaches and the existing obstacles for PLC treatment.

17.
Lab Invest ; 101(11): 1484-1493, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34446806

RESUMO

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3'-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH.

19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 619-623, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323040

RESUMO

Objective: To prepare and characterize D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) modified arginine deiminase (ADI) sulfobutyl-ß-Cyclodextrin liposome nanoparticles (ATCL), and to investigate the pharmacokinetic characteristics of ATCL in animals. Methods: The reverse evaporation method was used to prepare ATCL, and the particle size and Zeta potential of ATCL were measured. Thiosemicarbazone-diacetylmonooxime colorimetric method was used to measure the activity of ADI. After intravenous administration, blood was drawn at set intervals of time and the enzyme activity in the plasma was measured. Enzyme activity-time curve was drawn subsequently and Debris Assessment Software (DAS) 2.1.1 was used to analyze the pharmacokinetic characteristics. Results: The particle size and the potential of ATCL were (216.1±13.6) nm and (-19.4±2.1) mV, respectively. The optimal temperature and optimal pH for the catalytic reaction of ADI and ATCL were the same, both being 37 ℃ and pH6.5. Results of the analysis showed that the AUC (0-168 h), MRT (0-168 h), C max, T max, and t 1/2 of ATCL were 3.99, 2.56, 1.58, 3.2, and 9.88 times those of free ADI, respectively. Compared with ADI, the bioavailability of ATCL increased by 298.54%. Conclusion: ATCL prepared in the study can effectively improve the enzyme activity and bioavailability of ADI in Sprague-Dawley rats.


Assuntos
Hidrolases , Nanopartículas , Animais , Arginina , Lipídeos , Polietilenoglicóis , Ratos , Ratos Sprague-Dawley
20.
Virus Res ; 303: 198506, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34271040

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) have spread globally and led to the limited choice of antimicrobial treatment of K. pneumoniae-induced infections. Bacteriophages are considered as an effective strategy against bacterial infections. In this study, we isolated a novel Klebsiella phage BUCT556A with lytic activity against KPC-producing K. pneumoniae, which was a multi-drug resistant isolate. Phage BUCT556A had a symmetrical head and a long, non-contractile tail, belonging to the family Siphoviridae, order Caudoviridae. Phage BUCT556A had a relatively narrow host range, and a medium burst size of 91 PFU/cell. It was stable at broad temperature/pH range, and exhibited good tolerance to chloroform. The genome of phage BUCT556A was a 49, 376-bp linear double-stranded DNA molecule with average G + C content of 50.2%, and contained 75 open reading frames. There was no tRNA, antibiotic resistance, toxin, virulence related genes or lysogen-formation gene clusters detected in the genome of phage BUCT556A. Phylogenetic analyses based on the major capsid protein Mcp suggested that this phage had a close relationship with Klebsiella phage KLPN1. Together, through phenotypic combined with genomic DNA sequencing and analyses, our study suggests that phage BUCT556A has the potential to be used as a bacterial treatment tool for multidrug-resistant strains K. pneumoniae.

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