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1.
J Hazard Mater ; 469: 134022, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38484662

RESUMO

Sulfidized nanoscale zero-valent iron (S-nZVI) showed excellent removal capacity for cadmium (Cd) in aqueous phase. However, the remediation effects of S-nZVI on Cd-contaminated sediment and its interactions with microorganisms in relation to Cd fate remain unclear. The complexity of the external environment posed a challenge for Cd remediation. This study synthesized S-nZVI with different S and Fe precursors to investigate the effect of precursors and applied the optimal material to immobilize Cd in sediments. Characterization analysis revealed that the precursor affected the morphology, Fe0 crystallinity, and the degree of oxidation of the material. Incubation experiments demonstrated that the immobilization efficiency of Cd using S-nZVIFe3++S2- (S/Fe = 0.14) reached the peak value of 99.54%. 1% and 5% dosages of S-nZVI significantly reduced Cd concentration in the overlying water, DTPA-extractable Cd content, and exchangeable (EX) Cd speciation (P < 0.05). Cd leaching in sediment and total iron in the overlying water remained at low levels during 90 d of incubation. Notably, each treatment maintained a high Cd immobilization efficiency under different pH, water/sediment ratio, organic acid, and coexisting ion conditions. Sediment physicochemical properties, functional bacteria, and a range of adsorption, complexation and precipitation of CdS effects dominated Cd immobilization.


Assuntos
Ferro , Poluentes Químicos da Água , Ferro/química , Cádmio/química , Poluentes Químicos da Água/química , Água , Adsorção
2.
Water Res ; 253: 121309, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367381

RESUMO

Antibiotics and antibiotic resistance genetic pollution have become a global environmental and health concern recently, with frequent detection in various environmental media. Therefore, finding ways to control antibiotics and antibiotic resistance genes (ARGs) is urgently needed. Nano zero-valent iron (nZVI) has shown a positive effect on antibiotics degradation and restraining ARGs, making it a promising solution for controlling antibiotics and ARGs. However, given the current increasingly fragmented research focus and results, a comprehensive review is still lacking. In this work, we first introduce the origin and transmission of antibiotics and ARGs in various environmental media, and then discuss the affecting factors during the degradation of antibiotics and the control of ARGs by nZVI and modified nZVI, including pH, nZVI dose, and oxidant concentration, etc. Then, the mechanisms of antibiotic and ARGs removal promoted by nZVI are also summarized. In general, the mechanism of antibiotic degradation by nZVI mainly includes adsorption and reduction, while promoting the biodegradation of antibiotics by affecting the microbial community. nZVI can also be combined with persulfates to degrade antibiotics through advanced oxidation processes. For the control of ARGs, nZVI not only changes the microbial community structure, but also affects the proliferation of ARGs through affecting the fate of mobile genetic elements (MGEs). Finally, some new ideas on the application of nZVI in the treatment of antibiotic resistance are proposed. This paper provides a reference for research and application in this field.


Assuntos
Antibacterianos , Poluentes Químicos da Água , Antibacterianos/farmacologia , Ferro/química , Oxirredução , Resistência Microbiana a Medicamentos/genética , Adsorção , Poluentes Químicos da Água/química
3.
Environ Sci Pollut Res Int ; 31(7): 10950-10966, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38214863

RESUMO

The pollution of antibiotics, specifically ciprofloxacin (CIP), has emerged as a significant issue in the aquatic environment. Advanced oxidation processes (AOPs) are capable of achieving stable and efficient removal of antibiotics from wastewater. In this work, biochar-supported sulfidized nanoscale zero-valent iron (S-nZVI/BC) was adopted to activate persulfate (PS) for the degradation of CIP. The impacts of different influencing factors such as S/Fe molar ratios, BC/S-nZVI mass ratios, PS concentration, S-nZVI/BC dosage, CIP concentration, initial pH, coexisting anions, and humic acid on CIP degradation efficiency were explored by batch experiments. The results demonstrated that the highest degradation ability of S-nZVI/BC was achieved when the S/Fe molar ratio was 0.07 and the BC/S-nZVI mass ratio was 1:1. Under the experimental conditions with 0.6 g/L S-nZVI/BC, 2 mmol/L PS, and 10 mg/L CIP, the degradation rate reached 97.45% after 90 min. The S-nZVI/BC + PS system showed significant degradation in the pH range from 3 to 9. The coexisting anions affected the CIP degradation efficiency in the following order: CO32- > NO3- > SO42- > Cl-. The radical quenching experiments and electron paramagnetic resonance (EPR) revealed that oxidative species, including SO4•-, HO•, •O2-, and 1O2, all contribute to the degradation of CIP, in which •O2- plays a particularly prominent role. Furthermore, the probable degradation pathway of CIP was explored according to the 12 degradation intermediates identified by LC-MS. This study provides a new idea for the activation method of PS and presents a new approach for the treatment of aqueous antibiotics with highly catalytic active nanomaterials.


Assuntos
Carvão Vegetal , Ciprofloxacina , Poluentes Químicos da Água , Ferro , Poluentes Químicos da Água/análise , Antibacterianos , Água
4.
Small ; 20(25): e2311228, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38225708

RESUMO

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.


Assuntos
Microambiente Tumoral , Humanos , Animais , Terapia por Ultrassom/métodos , Neoplasias/terapia , Compostos Inorgânicos/química , Espécies Reativas de Oxigênio/metabolismo
5.
Nat Cell Biol ; 25(12): 1746-1757, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38012403

RESUMO

The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this is regulated. Here we found that nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells is required to maintain nerve fibres in adult bone marrow. In nerveless bone marrow, steady-state haematopoiesis was normal but haematopoietic and vascular regeneration were impaired after myeloablation. LepR+ cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sprouting in the bone marrow and haematopoietic and vascular regeneration. Nerves promoted regeneration by activating ß2 and ß3 adrenergic receptor signalling in LepR+ cells, and potentially in adipocytes, increasing their production of multiple haematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR+ cells thus promote bone marrow regeneration through a reciprocal relationship in which LepR+ cells sustain nerves by synthesizing NGF and nerves increase regeneration by promoting the production of growth factors by LepR+ cells.


Assuntos
Medula Óssea , Receptores para Leptina , Medula Óssea/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Células da Medula Óssea/metabolismo , Fator de Crescimento Neural/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Regeneração Nervosa
6.
Environ Sci Pollut Res Int ; 30(55): 117892-117908, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37874516

RESUMO

Modified nanoscale zero-valent iron (NZVI) exhibited great potential for the remediation of heavy metal contaminated river sediments, but its mechanisms and environmental risks are still unclear. This study systematically discussed the performance and the mechanisms of modified NZVI materials, i.e., sodium alginate-coated NZVI (SNZVI), rhamnolipid-coated NZVI (RNZVI), and graphene oxide-loaded NZVI (GNZVI), for the stabilization of Cd in sediment, with the exploration of their stability to Cd at various pH values and Fe dissolution rate. Compared with the control, the toxicity characteristic leaching procedure (TCLP) leachable Cd decreased by 52.66-96.28%, and the physiologically based extraction test (PBET) extractable Cd decreased by 44.68-70.21% after 56 days of incubation with the immobilization efficiency varying according to GNZVI > RNZVI > SNZVI > NZVI. Besides, the adsorption behavior of Cd on materials was fitted with the Freundlich model and classified as an endothermic, spontaneous, and chemical adsorption process. SEM-EDX, XRD, and FTIR results verified that the stabilization mechanisms of Cd were principally based on the adsorption, complexation of Cd2+ with secondary Fe minerals (including Fe2O3, γ-Fe2O3, and γ-FeOOH) and precipitation (Cd(OH)2). From the risk assessment results, it was observed that the materials were favorable for Cd stabilization at a pH range from 7 to 11, meanwhile, the leaching concentration of Fe in the overlying water was detected below the limit value. These findings pave the way to developing an effective strategy to remediate Cd contaminated river sediments.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes Químicos da Água , Ferro , Cádmio , Rios , Adsorção
7.
Environ Sci Pollut Res Int ; 30(46): 101933-101962, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37659023

RESUMO

Over the past decade, sulfidized nanoscale zero-valent iron (S-nZVI) has been developed as a promising tool for the remediation of contaminated soil, sediment, and water. Although most studies have focused on applying S-nZVI for clean-up purposes, there is still a lack of systematic summary and discussion from its synthesis, application, to toxicity assessment. This review firstly summarized and compared the properties of S-nZVI synthesized from one-step and two-step synthesis methods, and the modification protocols for obtaining better stability and reactivity. In the context of environmental remediation, this review outlined an update on the latest development of S-nZVI for removal of heavy metals, organic pollutants, antibiotic resistance genes (ARGs), and antibiotic resistant bacteria (ARB) and also discussed the underlying removal mechanisms. Environmental factors affecting the remediation performance of S-nZVI (e.g., humic acid, coexisting ions, S/Fe molar ratio, pH, and oxygen condition) were highlighted. Besides, the application potential of S-nZVI in advanced oxidation processes (AOP), especially in activating persulfate, was also evaluated. The toxicity impacts of S-nZVI on the environmental microorganism were described. Finally, the future challenges and remaining restrains to be resolved for better applicability of S-nZVI are also proposed. This review could provide guidance for the environmental remediation with S-nZVI-based technology from theoretical basis and practical perspectives.

8.
J Hazard Mater ; 458: 132028, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37459757

RESUMO

Post-sulfidated nanoscale zero-valent iron with a controlled FeSX shell thickness deposited on biochar (S-nZVI/BC) was synthesized to degrade tetrabromobisphenol A (TBBPA). Detailed characterizations revealed that the increasing sulfidation degree altered shell thickness/morphology, S content/speciation/distribution, hydrophobicity, and electron transfer capacity. Meanwhile, the BC improved electron transfer capacity and hydrophobicity and inhibited the surface oxidation of S-nZVI. These properties endowed S-nZVI/BC with highly reactive (∼8.9-13.2 times) and selective (∼58.4-228.9 times) over nZVI/BC in TBBPA transformation. BC modification improved the reactivity and selectivity of S-nZVI by 1.77 and 1.96 times, respectively. The difference of S-nZVI/BC in reactivity was related to hydrophobicity and electron transfer, particularly FeSX shell thickness and morphology. Optimal shell thickness of ∼32 nm allowed the maximum association between Fe0 core and exterior FeSX, resulting in superior reactivity. A thicker shell with abundant networks increased the roughness but decreased the surface area and electron transfer. The higher [S/Fe]surface and [S/Fe]particle were conducive to the selectivity, and [S/Fe]particle was more influential than [S/Fe]surface on selectivity upon similar hydrophobicity. The solvent kinetic isotope effects (SKIEs) exhibited that increasing [S/Fe]dose tuned the relative contributions of atomic H and electron in TBBPA debromination but failed to alter the dominant debromination pathway (i.e., direct electron transfer) in (S)-nZVI/BC systems. Mechanism of electron transfer rather than atomic H contributed to higher selectivity. This work demonstrated that S-nZVI/BC was a prospective material for the remediation of TBBPA-contaminated groundwater.

9.
J Cancer Res Clin Oncol ; 149(12): 9529-9542, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37219743

RESUMO

BACKGROUND: Acquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. METHODS: The tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan-Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. RESULTS: In this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body's immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. CONCLUSION: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.


Assuntos
Subpopulações de Linfócitos B , Neoplasias Pulmonares , Lesões por Radiação , Camundongos , Animais , Camundongos Nus , Subpopulações de Linfócitos B/patologia , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Tolerância a Radiação , Apoptose
10.
Gels ; 9(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36826268

RESUMO

Postoperative adhesion is a common post-surgery complication formed between the surface of the body cavity, ranging from a layer of connective tissue to a fibrous bridge containing blood vessels and nerve tissue. Despite achieving a lot of progress, the mechanisms of adhesion formation still need to be further studied. In addition, few current treatments are consistently effective in the prevention of postoperative adhesion. Hydrogel is a kind of water-expanding crosslinked hydrophilic polymer network generated by a simple reaction of one or more monomers. Due to the porous structure, hydrogels can load different drugs and control the drug release kinetics. Evidence from existing studies has confirmed the feasibility and superiority of using hydrogels to counter postoperative adhesions, primarily due to their outstanding antifouling ability. In this review, the current research status of hydrogels as anti-adhesion barriers is summarized, the character of hydrogels in the prevention of postoperative adhesion is briefly introduced, and future research directions are discussed.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 280: 121552, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-35759931

RESUMO

Cysteine (Cys) is one of the most important biothiols that plays a crucial role in many physiological and pathological processes, and therefore it is of great importance to detect and analyze Cys in subcellular environments, such as in lysosomes. However, only a few fluorescent probes were reported to be capable of detecting Cys in lysosomes selectively. In this wok, we designed and developed a simple, accessible flavone-based fluorescent probe LFA for detecting Cys in lysosomes. Morpholine was employed as the targeting unit for lysosome, and acrylate group was chosen as the Cys-response unit. The probe was easily prepared by a two-step procedure and displayed large Stokes shift, high sensitivity, turn-on response toward Cys over homocysteine (Hcy), glutathione (GSH), and other amino acids. With low cytotoxicity and good cell permeability, the probe could be successfully applied for fluorescence imaging of Cys in living cells. Furthermore, colocalization experiment revealed that lysosomal-targetable ability of LFA was significant. These results indicated that such simple fluorescent probe could provide a promising tool for detection of lysosomal Cys in living biological systems.


Assuntos
Cisteína , Corantes Fluorescentes , Cisteína/análise , Flavonoides/análise , Corantes Fluorescentes/química , Glutationa/análise , Células HeLa , Homocisteína/análise , Humanos , Lisossomos/metabolismo , Espectrometria de Fluorescência
12.
Cell Death Discov ; 8(1): 264, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577774

RESUMO

Hepatocellular carcinoma (HCC) is a common digestive malignant tumor with high morbidity and mortality worldwide, however, the treatment of HCC and prognosis of patients are not optimistic, finding more effective treatments are imperative. Taraxacum officinale (L.) Weber ex F.H.Wigg is a perennial herb of compositae, and our study has demonstrated that Taraxacum officinale polysaccharide has certain anti-tumor effect on HCC cells. Taraxasterol (TS) is a natural product extracted from Taraxacum officinale with strong physiological, pharmacological and biological activities, but the effect of TS on HCC is yet to be determined. Therefore, the aim of this study is to explore the effect of dandelion sterol on HCC in vivo and in vitro. The results showed that TS significantly inhibited the proliferation, induced apoptosis and blocked cell cycle in HCC cell lines HepG2 and Huh7 cells in vitro. TS inhibited the tumor growth of H22 bearing mice and the expression of Ki67 in vivo. More importantly, TS regulated the immunity of H22 bearing mice by elevating the ratio of CD4+ T cells in spleen, and increasing the number of T cell infiltration in tumor tissue. Except immunomodulation, the mechanism of tumor growth inhibition may be related to the regulation of apoptosis related proteins and IL-6/STAT3 pathway. TS significantly inhibited the growth of HCC cells both in vitro and in vivo. The study would provide a theoretical basis for the new application of TS and the adjuvant treatment of malignant tumor with traditional Chinese medicine.

13.
J Environ Manage ; 299: 113682, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34526277

RESUMO

The treatment cost for Cl- removal by Friedel's salt precipitation depended significantly on utilization rate of the precipitant aluminate. In this study, effects of Ca/Al molar ratio, reaction time, temperature and Al/Cl molar ratio were investigated to maximize Al utilization rate for Cl- removal from flue gas desulfurization wastewater. Batch results showed that the maximum Al utilization rate of 55.8-60.3% was obtained at Ca/Al ratio of 3.00, reaction time of 90 min, temperature of 35 °C and Al/Cl ratio of 0.50 regardless of the initial Cl- concentration. The precipitate obtained at the highest Al utilization rate had the highest interlayer spacing, the best crystal integrity, and the strongest binding energy of the Al-OH bond. The optimized condition made ion exchange between Cl- and OH- easier, and obtained more stable Friedel's salt structure to adsorb Cl-. Pilot-scale results showed that maximizing Al utilization rate with low dosages of precipitants had insignificant effects on the removal of Mg2+, Ca2+ and sulfate compared to the strategy to maximize Cl-, but enhanced Al utilization rate from 38.2% to 56.4%. Economic analysis showed that enhancing Al utilization rate greatly reduced treatment cost of the Friedel's salt precipitation method by 30.5%, and made the two-stage desalination process more feasible and worth popularizing.


Assuntos
Cloretos , Águas Residuárias , Óxido de Alumínio , Cloreto de Cálcio , Cloretos/análise
14.
Am J Mens Health ; 15(3): 15579883211017033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34036824

RESUMO

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14-1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13-1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09-1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.


Assuntos
Aromatase , Neoplasias da Próstata , Alelos , Aromatase/genética , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo Genético , Neoplasias da Próstata/genética
15.
J Hazard Mater ; 417: 126054, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992018

RESUMO

In this study, a five-stage stepwise precipitation process, including pre-sedimentation, magnesium removal, gypsum precipitation, ettringite precipitation and calcium removal, was proposed as a softening pretreatment for zero liquid discharge system for flue gas desulfurization wastewater. Batch tests and long-term bench-scale experiment showed that magnesium, sulfate and calcium were efficiently removed with efficiencies all above 98.0%, leaving a clean effluent majorly containing NaCl and NaOH. The precipitated CaSO4, CaCO3, Mg(OH)2 and ettringite were completely separated by stepwise precipitation, and the purity of Mg(OH)2 and ettringite were further enhanced by washing and soaking treatment. CaSO4 and CaCO3 can be directly recycled as gypsum product and desulfurizing agent within the power plant, while Mg(OH)2 and ettringite presented proper particle size and excellent thermal properties as a synergistic flame retardant. The flame retardancy of ethylene vinyl acetate copolymer were greatly improved when blended with recovered Mg(OH)2 and ettringite, and possessed better performance by blending them together because ettringite could act as a dispersing and compatible agent of Mg(OH)2, and relieve the intensity of smoke releasing. Chemical sludge recovery compensates the total cost of the five-stage process by 45.0%, and makes the process technically versatile, economically beneficial and environmentally friendly without solid waste production.


Assuntos
Retardadores de Chama , Águas Residuárias , Sulfato de Cálcio , Precipitação Química , Esgotos , Sulfatos
16.
Cell Cycle ; 20(2): 211-224, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404279

RESUMO

Combining targeted therapeutic agents is an attractive cancer treatment strategy associated with high efficacy and low toxicity. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is an essential factor in DNA damage repair. Studies from us and others have revealed that DNA-PKcs also plays an important role in normal mitosis progression. Histone deacetylase (HDACs) inhibitors commonly lead to mitotic aberration and have been approved for treating various cancers in the clinic. We showed that DNA-PKcs depletion or kinase activity inhibition increases cancer cells' sensitivity to HDACs inhibitors in vitro and in vivo. DNA-PKcs deficiency significantly enhances HDACs inhibitors (HDACi)-induced mitotic arrest and is followed by apoptotic cell death. Mechanistically, we found that DNA-PKcs binds to HDAC6 and facilitates its acetylase activity. HDACi is more likely to impair HDAC6-induced deacetylation of HSP90 and abrogate HSP90's chaperone function on Aurora A, a critical mitotic kinase that regulates centrosome separation and mitotic spindle assembly in DNA-PKcs-deficient cells. Our current work indicates crosstalk between DNA-PKcs and HDACs signaling pathways, and highlights that the combined targeting of DNA-PKcs and HDACs can be used in cancer therapy. Abbreviations: DNA-PKcs, DNA-dependent protein kinase catalytic subunit, HDACs, Histone deacetylases, DSBs, DNA double-strand breaks, ATM, ataxia telangiectasia mutated, ATR, ATM-Rad3-related.


Assuntos
Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Desacetilase 6 de Histona/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/metabolismo , Divisão do Núcleo Celular/genética , Divisão do Núcleo Celular/fisiologia , Dano ao DNA/genética , Reparo do DNA/genética , Desacetilase 6 de Histona/genética , Humanos , Proteínas Supressoras de Tumor/metabolismo
17.
Nat Prod Res ; 35(12): 2002-2009, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31523980

RESUMO

The investigation on the stems and leaves of Clausena lenis led to the isolation of a previously undescribed carbazole alkaloid, clausenalenine A (1), along with seven known analogues (2-8). The structure of 1 was elucidated based on comprehensive spectroscopic analyses and the known compounds were identified by comparisons with data reported in the literatures. All known compounds (2-8) were isolated from C. lenis for the first time. All isolated compounds were evaluated for their neuroprotective activities against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Compounds 1-8 showed significant neuroprotective effects with EC50 values ranging from 0.68 to 18.76 µM.


Assuntos
Alcaloides/farmacologia , Clausena/química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Alcaloides/química , Carbazóis/química , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray
18.
J Agric Food Chem ; 68(44): 12326-12335, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33107299

RESUMO

Toona sinensis, popularly known as Chinese toon or Chinese mahogany, is a perennial deciduous arbor belonging to the genus Toona in the Meliaceae family, which is widely distributed and cultivated in eastern and southeastern Asia. Its fresh young leaves and buds have been consumed as a very popular nutritious vegetable in China and confirmed to display a wide variety of biological activities. To investigate the chemical constituents and their potential health benefits from the fresh young leaves and buds of T. sinensis, a phytochemical study on its fresh young leaves and buds was therefore undertaken. In our current investigation, 16 limonoids (1-16), including four new limonoids, toonasinenoids A-D (1-4), and a new naturally occurring limonoid, toonasinenoid E (5), were isolated and characterized from the fresh young leaves and buds of T. sinensis. The chemical structures and absolute configurations of limonoids 1-5 were elucidated by comprehensive spectroscopic data analyses. All known limonoids (6-16) were identified via comparing their experimental spectral data containing mass spectrometry data, 1H and 13C nuclear magnetic resonance data, and optical rotation values to the data reported in the literature. All known limonoids (6-16) were isolated from T. sinensis for the first time. Furthermore, the neuroprotective effects of all isolated limonoids 1-16 against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells were assessed in vitro. Limonoids 1-16 exhibited notable neuroprotective activities, with EC50 values in the range from 0.27 ± 0.03 to 17.28 ± 0.16 µM. These results suggest that regular consumption of the fresh young leaves and buds of T. sinensis might prevent the occurrence and development of Parkinson's disease (PD). Moreover, the isolation and characterization of these limonoids that exhibit notable neuroprotective activities from the fresh young leaves and buds of T. sinensis could be very significant for researching and developing new neuroprotective drugs used for the prevention and treatment of PD.


Assuntos
Medicamentos de Ervas Chinesas/química , Limoninas/química , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Folhas de Planta/química , Brotos de Planta/química , Toona/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Limoninas/isolamento & purificação , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/isolamento & purificação
19.
Oxid Med Cell Longev ; 2020: 8905860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32934763

RESUMO

With more powerful penetrability and ionizing capability, high energetic neutron radiation (HENR) often poses greater threats than photon radiation, especially on such occasions as nuclear bomb exposure, nuclear accidents, aerospace conduction, and neutron-based radiotherapy. Therefore, there emerges an urgent unmet demand in exploring highly efficient radioprotectants against HENR. In the present study, high-throughput 14.1 MeV neutrons were generated by the high-intensity D-T fusion neutron generator (HINEG) and succeeded in establishing the acute radiation syndrome (ARS) mouse model induced by HENR. A series of preclinical studies, including morphopathological assessment, flow cytometry, peripheral complete blood, and bone marrow karyocyte counting, were applied showing much more serious detriments of HENR than the photon radiation. In specific, it was indicated that surviving fraction of polydatin- (PD-) treated mice could appreciably increase to up to 100% when they were exposed to HENR. Moreover, polydatin contributed much in alleviating the HENR-induced mouse body weight loss, spleen and testis indexes decrease, and the microstructure alterations of both the spleen and the bone marrow. Furthermore, we found that the HENR-damaged hematopoiesis was greatly prevented by PD treatment in such aspects as bone marrow hemocytogenesis, splenocytes balancing, or even the peripheral blood cellularity. The additional IHC investigations revealed that PD could exert potent hematopoiesis-promoting effects against HENR via suppressing apoptosis and promoting the antioxidative enzymes such as HO-1.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Glucosídeos/farmacologia , Hematopoese/efeitos dos fármacos , Nêutrons , Estilbenos/farmacologia , Animais , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos da radiação , Glucosídeos/administração & dosagem , Hematopoese/efeitos da radiação , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Radiação Ionizante , Sirtuína 1/metabolismo , Baço/patologia , Estilbenos/administração & dosagem , Análise de Sobrevida
20.
Bioorg Chem ; 102: 104101, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32721778

RESUMO

Three new carbazole alkaloids, zanthoaustrones A-C (1-3), as well as nine known compounds 4-12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1-12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1-12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC50 values displaying IC50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Raízes de Plantas/química , Zanthoxylum/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Relação Estrutura-Atividade
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