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1.
J Mol Model ; 27(12): 363, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825997

RESUMO

The study of the reaction between plutonium and nitrogen is helpful in further understanding the interaction between plutonium and air molecules. Currently, there is no research on the microscopic reaction mechanism of plutonium nitridation reactions. Therefore, the microscopic mechanism of the Pu with N2 gas phase reaction is explored in this study, based on density functional theory (DFT) using different basis functions. In this paper, the geometry of stationary points on the potential energy surface is optimized. In addition, the transition states are verified by frequency analysis and intrinsic reaction coordination (IRC). Finally, we obtained the reaction potential energy curve and micro reaction pathways. Analysis of the reaction mechanism shows that the reaction of Pu with N2 has two pathways. Pathway 1 (Pu + N2 → R1 → TS1 → PuN2) has a T-shaped transition state and pathway 2 (Pu + N2 → R2 → TS2 → PuN + N) has an L-shaped transition state. Both transition states have only one imaginary frequency. According to the comparison of the energy at each stagnation point along the two pathways, and the heat energy emitted by the two reaction paths, we found that pathway 1 is the main reaction pathway. The nature of Pu-N bonding evolution along the pathways was studied by atoms in molecules (AIM) and electron localization function (ELF) topological approaches. In order to analyze the role of the plutonium atom 5f orbital in the reaction, the variation in density state along the pathways was measured. Results show that the 5f orbital mainly contributes to the formation of Pu-N bonds, and the influence of temperature on the reaction rate is revealed by calculating the rate constants of the two reaction pathways.

2.
Biochem Biophys Res Commun ; 580: 48-55, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34624569

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal human cancers with a lower 5-year survival rate. N6-methyladenosine (m6A) methylation, an important epigenetic modification, has been reported to associate with physiological and pathological processes of cancers. However, its role in ESCC remains unclear. In this work, we found that the m6A levels were elevated in ESCC cancer tissues and ESCC cells. The PPI network demonstrated that METTL3, METTL14, WTAP, RBM15, and KIAA1429 were all significantly associated with each other. Moreover, we found a significant upregulation of METTL3 mRNA and protein amounts in ESCC tissues. The METTL3 mRNA expression level of tissues had associations with ESCC differentiation extent and sex (p < 0.05). The METTL3 mRNA expression level of tissues, sensitivity for diagnosing ESCC was 75.00%, specificity was 72.06% and area under the ROC curve was 0.8030. Depletion of METTL3 markedly diminished m6A levels in human ESCC cell lines and METTL3 overexpression restored the reduction in m6A levels. These results suggested that METTL3 is the primary enzyme that modulates m6A methylation and a critical regulatory factor in ESCC. Additionally, METTL3 knockdown significantly suppressed the ESCC cell proliferation, while METTL3 overexpression markedly promoted ESCC cell proliferation both in cell and animal models. These results demonstrated that METTL3 promotes ESCC development. Furthermore, METTL3 may modulate the cell cycle of ESCC cells through a p21-dependent pattern. METTL3-guided m6A modification may contribute to the progression of ESCC via the p21-axis. Our study is the first investigation to report that METTL3-mediated m6A methylation plays a crucial role in ESCC oncogenesis and highlights that METTL3 might be a potential biomarker and therapeutic target for ESCC patients.

3.
J Clin Lab Anal ; 35(11): e24035, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34606646

RESUMO

BACKGROUND: Humoral immunity is thought to play a central role in mediating the immunopathogenesis of dengue virus (DENV) infection; however, the B-cell responses elicited by primary DENV2 infection are incompletely understood. Follicular helper T cells (Tfh) are important to promote B-cell activation and differentiation. METHODS: The present study analyzed the detailed dynamic changes of circulating B-cell subsets and Tfh (cTfh) using flow cytometry to explore their responses to DENV2 infection. RESULTS: Thirty-six patients with DENV2 and 21 healthy individuals were included. The results showed that CD27+ CD38+ plasmablasts emerged after DENV2 infection, and correlated with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh, which increased after DENV2 infection, and correlated with DENV2 RNA viral loads. Significantly low levels of CD27- naïve B cells, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells (Breg) were observed after DENV2 infection, which correlated negatively with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh cells. CONCLUSION: Overall, these results provide insights into the DENV2-elicited B-cell response and revealed previously unidentified CD24hi CD27hi and CD24hi CD38hi Breg responses to DENV2 infection.

4.
Chem Commun (Camb) ; 57(74): 9390-9393, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528958

RESUMO

Herein, a highly regioselective alkylation of propargylic carbonates for trisubstituted allenes with alkyl 1,4-dihydropyridine derivatives (1,4-DHPs) is developed via a photoredox/nickel dual-catalyzed process, which represents the first direct approach to access alkylated allene products without alkyl organometallic reagents. This method features a broad substrate scope and mild conditions. A hypothetical mechanism with an alkyl radical and an allenyl Ni(III) species is proposed. Benzylation products were also obtained to be the complement building blocks for the potential synthesis of pharmaceuticals.


Assuntos
Alcadienos/síntese química , Carbonatos/química , Níquel/química , Alcadienos/química , Alquilação , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Estereoisomerismo
5.
Cell Death Dis ; 12(8): 758, 2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34333526

RESUMO

Heterogeneous nuclear ribonucleoprotein L (hnRNPL) is a type of RNA binding protein that highly expressed in a variety of tumors and plays a vital role in tumor progression. However, its post-translational regulation through ubiquitin-mediated proteolysis and the cellular mechanism responsible for its proteasomal degradation remains unclear. F-box proteins (FBPs) function as the substrate recognition subunits of SCF ubiquitin ligase complexes and directly bind to substrates. The aberrant expression or mutation of FBPs will lead to the accumulation of its substrate proteins that often involved in tumorigenesis. Here we discover FBXO16, an E3 ubiquitin ligase, to be a tumor suppressor in ovarian cancer, and patients with the relatively high expression level of FBXO16 have a better prognosis. Silencing or depleting FBXO16 significantly enhanced ovarian cancer cell proliferation, clonogenic survival, and cell invasion by activating multiple oncogenic pathways. This function requires the F-box domain of FBXO16, through which FBXO16 assembles a canonical SCF ubiquitin ligase complex that constitutively targets hnRNPL for degradation. Depletion of hnRNPL is sufficient to inactive multiple oncogenic signaling regulated by FBXO16 and prevent the malignant behavior of ovarian cancer cells caused by FBXO16 deficiency. FBXO16 interacted with the RRM3 domain of hnRNPL via its C-terminal region to trigger the proteasomal degradation of hnRNPL. Failure to degrade hnRNPL promoted ovarian cancer cell proliferation in vitro and tumor growth vivo, phenocopying the deficiency of FBXO16 in ovarian cancer.

6.
Int J Cosmet Sci ; 43(5): 495-509, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34312881

RESUMO

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

7.
Anal Chem ; 93(29): 10196-10203, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34270226

RESUMO

Ultrasensitive detection of metallic elements in liquids has attracted considerable attention in fields such as environmental pollution monitoring and drinking water quality control. Hence, it is of great significance to develop a sensitive and simultaneous detection strategy for multiple metal elements in liquid. Laser-induced breakdown spectroscopy (LIBS) technology shows unique advantages because of its simple, rapid, and real-time in situ detection, but the laser energy will be greatly attenuated in the liquids; thus, the sensitivity of LIBS for direct detection of metal elements in liquid samples will decrease sharply. In this study, inspired by the structure of Stenocara beetle's back, a superhydrophobic biomimetic interface with hydrophilic array was prepared for enriching low-concentration targets into detection regions, and the biomimetic array LIBS (BA-LIBS) was successfully established. The ultrasensitive and simultaneous detection of nine metal elements in drinking water was realized based on the effective enrichment method. The limits of detection of the nine metal elements in mixed solution ranged from 8.3 ppt to 13.49 ppb. With these excellent properties, this facile and ultrasensitive BA-LIBS strategy might provide a new idea for the prevention and control of metal hazards in the liquid environment.


Assuntos
Biomimética , Água Potável , Monitoramento Ambiental , Lasers , Análise Espectral
8.
Org Biomol Chem ; 19(25): 5659, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34137424

RESUMO

Correction for 'Visible-light-mediated borylation of aryl and alkyl halides with a palladium complex' by Jia-Hui Zhao, et al., Org. Biomol. Chem., 2020, 18, 4390-4394, DOI: 10.1039/D0OB00028K.

9.
J Colloid Interface Sci ; 602: 748-755, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171745

RESUMO

Highly active and efficient photocatalysts are crucial for the exploration of ammonia synthesis because of the serious problem of energy deficiency. La2TiO5 (LTO) perovskite materials have great advantages in the field of photocatalytic nitrogen fixation because of the broadly diversified properties. The rational design of surface defect is a valid method to modulate photoinduced charge traps and create defect energy levels, especially it is an effective way to suppress the photoinduced charge recombination. Herein, LTO was obtained by a simple sol-gel method and was further reduced by NaBH4 to introduce oxygen defect on its surface. UV-vis spectra proved that the surface defects could reduce the band gap value of samples, which is beneficial for improving photocatalytic nitrogen fixation activity. For the best photocatalytic samples with good cycle stability, the nitrogen fixation rate is 158.13 µmol·g-1·h-1. The mechanism of photocatalytic nitrogen fixation was proposed by the PL, XPS, and PEC results, which provided possibilities for exploring more promising perovskite catalysts in the field of nitrogen fixation.


Assuntos
Elétrons , Fixação de Nitrogênio , Amônia , Catálise , Recombinação Genética
10.
J Fish Dis ; 44(10): 1587-1594, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34165796

RESUMO

Spring viraemia of carp (SVC) caused by spring viraemia of carp virus (SVCV) can infect almost all fish of cyprinids, which bring huge economic losses to aquaculture. Glycoprotein (G), as the most important antigenic determinant protein of SVCV, is widely considered as an effective method against SVCV. In our previous study, we found that G3 (131 aa) is the potential dominant antigen epitope that induces strong immune responses similar to G protein (510 aa). Here, in order to further improve the immune effect, we reported a subunit vaccine (PEG-G3) constructed by PEG-modified dominant epitope protein (G3). The results of serum antibody production, enzyme activities and immune-related genes expression showed that PEG-G3 induces significantly stronger immune protective responses against SVCV than G3. PEG modification significantly increased the serum antibody level of the vaccine, which increased significantly after immunization and reached the peak at 21 day post-vaccination. T-AOC and AKP activities in the lowest concentration group (5 µg) of PEG-G3 were significantly higher than those in the highest concentration group (20 µg) of G3. In PEG-G3 group, the expression of almost all genes increased at least 4 times compared with the control group. After 14-day challenge, the RPS (relative percentage survival) of the highest concentration of PEG-G3 group was 53.6%, while that of G3 group is 38.9%. Therefore, this work shows that PEG modification and dominant epitope screening may be effective methods to improve the immune protective effect of vaccines and to resist the infection of aquatic animal viral diseases.


Assuntos
Carpas , Doenças dos Peixes/prevenção & controle , Imunização/veterinária , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/imunologia , Vacinas de Subunidades/imunologia , Vacinas Virais/imunologia , Animais , Epitopos/imunologia , Doenças dos Peixes/virologia , Imunidade , Infecções por Rhabdoviridae/prevenção & controle , Infecções por Rhabdoviridae/virologia , Vacinas de Subunidades/administração & dosagem , Vacinas Virais/administração & dosagem
11.
Phys Chem Chem Phys ; 23(31): 16707-16717, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34037001

RESUMO

Electrochemical techniques for ammonia synthesis are considered as an encouraging energy conversion technology to efficiently meet the challenge of nitrogen cycle balance. Herein, we find that TiO2(101)-supported Ni4 and Ni13 clusters can serve as efficient catalysts for electrocatalytic N2 reduction based on theoretical calculations. Electronic property calculations reveal the formation of electron-deficient Ni clusters on the TiO2 surface, which provides multiple active sites for N2 adsorption and activation. Theoretical calculation identifies the strongest activated configuration of N2* on the catalysts and confirms the potential-limiting step in the nitrogen reduction reaction (NRR). On Ni4-TiO2(101), N2* → NNH* is the potential-limiting step with a very small free energy increase (ΔG) of 0.24 eV (the corresponding overpotential is 0.33 V), while on Ni13-TiO2(101) the potential-limiting step occurs at NH* → NH2* with ΔG of 0.49 eV (the corresponding overpotential is 0.58 V). Moreover, the Nin-TiO2(101) catalyst, especially Ni13-TiO2(101), involves in a highly selective NRR even at the corresponding NRR overpotential. This work will enlighten material design to construct metal oxide supported transition metal clusters for the highly efficient NRR and NH3 synthesis.

12.
Front Immunol ; 12: 611711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763062

RESUMO

Background and Aims: There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients. Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model. Results: Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07-1.27; I 2, 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05-1.25; I 2, 78%), or a serious infection (RR, 1.49; 95% CI, 1.06-2.10; I 2, 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19-1.85; I 2, 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01-1.78; I 2, 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07-1.25; I 2, 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97-1.28; I 2, 81%; Pinteraction = 0.66). Conclusions: Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.


Assuntos
Cloridrato de Fingolimode/efeitos adversos , Imunossupressores/efeitos adversos , Infecções/epidemiologia , Infecções/etiologia , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Incidência , Infecções/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Razão de Chances , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco
13.
Cell Death Dis ; 12(4): 317, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767133

RESUMO

RNASET2 (Ribonuclease T2) functions as a tumor suppressor in preventing ovarian tumorigenesis. However, the mechanisms underlying the regulation of RNASET2 protein are completely unknown. Here we identified the F-box protein FBXO6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin E3 ligase for RNASET2. We found that the interaction between FBXO6 and RNASET2 induced RNASET2 instability through the ubiquitin-mediated proteasome degradation pathway. FBXO6 promoted K48-dependent ubiquitination of RNASET2 via its FBA domain. Through analysis of the TCGA dataset, we found that FBXO6 was significantly increased in ovarian cancer tissues and the high expression of FBXO6 was related to the poor overall survival (OS) of ovarian cancer patients at advanced stages. An inverse correlation between the protein levels of FBXO6 and RNASET2 was observed in clinic ovarian cancer samples. Depletion of FBXO6 promoted ovarian cancer cells proliferation, migration, and invasion, which could be partially reversed by RNASET2 silencing. Thus, our data revealed a novel FBXO6-RNASET2 axis, which might contribute to the development of ovarian cancer. We propose that inhibition of FBXO6 might represent an effective therapeutic strategy for ovarian cancer treatment.


Assuntos
Neoplasias Ovarianas/metabolismo , Ribonucleases/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Proteínas Culina/metabolismo , Feminino , Células HEK293 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ribonucleases/genética , Proteínas Ligases SKP Culina F-Box/genética , Transfecção , Proteínas Supressoras de Tumor/genética , Ubiquitinação
14.
Angew Chem Int Ed Engl ; 60(21): 11910-11918, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33605019

RESUMO

Efficient coupling solar energy conversion and N2 fixation by photocatalysis has been shown promising potentials. However, the unsatisfied yield rate of NH3 curbs its forward application. Defective typical perovskite, BaTiO3 , shows remarkable activity under an applied magnetic field for photocatalytic N2 fixation with an NH3 yield rate exceeding 1.93 mg L-1 h-1 . Through steered surface spin states and oxygen vacancies, the electromagnetic synergistic effect between the internal electric field and an external magnetic field is stimulated. X-ray absorption spectroscopy and density functional theory calculations reveal the regulation of electronic and magnetic properties through manipulation of oxygen vacancies and inducement of Lorentz force and spin selectivity effect. The electromagnetic effect suppresses the recombination of photoexcited carriers in semiconducting nanomaterials, which acts synergistically to promote N2 adsorption and activation while facilitating fast charge separation under UV-vis irradiation.

15.
Org Lett ; 23(3): 1107-1112, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33439665

RESUMO

A photocatalytic decarboxylative radical addition bifunctionalization cascade for the synthesis of functionalized alcohols is described. The catalytic cycle is completed through single-electron transfer. The advantages of this reaction are the commercially available materials, wide functional group compatibility, and mild conditions. Notably, some amino acids and bioactive carboxylic acids can provide corresponding products in moderate to good yields, reflecting the potential value in drug development.

16.
Contraception ; 103(4): 282-283, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33482142

RESUMO

A 31-year-old woman with epigastric pain underwent a "pi"-shaped copper bearing intrauterine device placement 11 years prior while lactating approximately 14 months after delivery. The patient experienced intermittent epigastric pain caused by the intrauterine device penetrating through the gastric wall. Removal required partial gastrectomy.


Assuntos
Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Dor Abdominal/etiologia , Adulto , Feminino , Humanos , Lactação
17.
Angew Chem Int Ed Engl ; 60(6): 3062-3070, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33112477

RESUMO

Molecular self-assembly has been widely used to develop nanocarriers for drug delivery. However, most of them have unsatisfactory drug loading capacity (DLC) and the dilemma between stimuli-responsiveness and stability, stagnating their translational process. Herein, we overcame these drawbacks using dynamic combinatorial chemistry. A carrier molecule was spontaneously and quantitatively synthesized, aided by co-self-assembly with a template molecule and an anti-cancer drug doxorubicin (DOX) from a dynamic combinatorial library that was operated by disulfide exchange under thermodynamic control. The highly selective synthesis guaranteed a stable yet pH- and redox- responsive nanocarrier with a maximized DLC of 40.1 % and an enhanced drug potency to fight DOX resistance in vitro and in vivo. Our findings suggested that harnessing the interplay between synthesis and self-assembly in complex chemical systems could yield functional nanomaterials for advanced applications.


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Nanotubos/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxirredução , Transplante Heterólogo
18.
Biol Trace Elem Res ; 199(5): 1686-1692, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32770328

RESUMO

The role of elements in physiological and pathological metabolic processes remains an unmet challenge in biomedical research and clinical applications. Herein, a visual elemental imaging of tumor tissue platform of a laser-induced breakdown spectroscopy (LIBS) was developed to initially understand anti-tumor mechanisms. The relative enrichment degree and heterogeneous spatial distributions of four elements (calcium, sodium, copper, and magnesium) of tumor tissue from different treated could be easy to visualize. In particular, significant differences in the distribution of elements were observed in tumor tissue from drug-loading complex (hydrogel/DOX) treatment group. Correspondingly, the analysis of histopathological morphology showed that the morphology and density of tumor tissue in hydrogel/DOX treatment group changed obviously by using hematoxylin and eosin (H&E) staining assay, meanwhile cleaved caspase-3 (caspase-3) and tumor necrosis factor (TNF-α) were expressed at high levels tumors tissue in hydrogel/DOX treatment group by using immunohistochemical (IHC) staining. These results would endow different biological elements with incredible potential to study the mechanisms of anti-tumor, which opens new direction and perspectives for the multi-elemental mapping of biological tissues, especially in clinic application. The integrated platform of DNA nanohydrogel drug carrier-based anti-tumor treatment combined with LIBS elemental imaging, via tail intravenous injection of saline, hydrogel, DOX, and hydrogel/DOX in breast cancer xenograft tumor mice. (A) The workflow is outlined starting from nanohydrogel drug carrier-based anti-tumor treatment. (B) Schematic diagram of LIBS imaging platform.


Assuntos
Neoplasias da Mama , Lasers , Animais , Neoplasias da Mama/tratamento farmacológico , Cobre , Feminino , Humanos , Magnésio , Camundongos , Análise Espectral
19.
Mol Microbiol ; 115(4): 739-757, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33155333

RESUMO

Both isomeric forms of alanine play a crucial role in bacterial growth and viability; the L-isomer of this amino acid is one of the building blocks for protein synthesis, and the D-isomer is incorporated into the bacterial cell wall. Despite a long history of genetic manipulation of Bacillus subtilis using auxotrophic markers, the genes involved in alanine metabolism have not been characterized fully. In this work, we genetically characterized the major enzymes involved in B. subtilis alanine biosynthesis and identified an alanine permease, AlaP (YtnA), which we show has a major role in the assimilation of D-alanine from the environment. Our results provide explanations for the puzzling fact that growth of B. subtilis does not result in the significant accumulation of extracellular D-alanine. Interestingly, we find that in B. subtilis, unlike E. coli where multiple enzymes have a biochemical activity that can generate alanine, the primary synthetic enzyme for alanine is encoded by alaT, although a second gene, dat, can support slow growth of an L-alanine auxotroph. However, our results also show that Dat mediates the synthesis of D-alanine and its activity is influenced by the abundance of L-alanine. This work provides valuable insights into alanine metabolism that suggests that the relative abundance of D- and L-alanine might be linked with cytosolic pool of D and L-glutamate, thereby coupling protein and cell envelope synthesis with the metabolic status of the cell. The results also suggest that, although some of the purified enzymes involved in alanine biosynthesis have been shown to catalyze reversible reactions in vitro, most of them function unidirectionally in vivo.

20.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300082

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor in humans. Chemotherapy is used for the treatment of CRC. However, the effect of chemotherapy remains unsatisfactory due to drug resistance. Growing evidence has shown that the presence of highly metastatic tumor stem cells, regulation of non­coding RNAs and the tumor microenvironment contributes to drug resistance mechanisms in CRC. Wnt/ß­catenin signaling mediates the chemoresistance of CRC in these three aspects. Therefore, the present study analyzed the abundant evidence of the contribution of Wnt/ß­catenin signaling to the development of drug resistance in CRC and discussed its possible role in improving the chemosensitivity of CRC, which may provide guidelines for its clinical treatment.


Assuntos
Neoplasias Colorretais , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas , Via de Sinalização Wnt , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
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