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1.
iScience ; 27(7): 110319, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39055957

RESUMO

The rhizosphere microbiome is important for plant health, yet their contributions to disease resistance and assembly dynamics remain unclear. This study employed rhizosphere microbiome transplantation (RMT) to delineate the impact of the rhizosphere microbiome and the immune response of eggplant (Solanum melongena) on resistance to bacterial wilt caused by Ralstonia solanacearum. We first identified disease-suppressive and disease-conducive rhizosphere microbiome in a susceptible tomato recipient. Using a non-destructive rhizobox and 16S rRNA amplicon sequencing, we monitored the dynamics of both microbiome types during the eggplant development. Most differences were observed at the early stage and then diminished over time. The suppressive microbiome maintained a higher proportion of initial community members throughout eggplant development and exhibited stronger deterministic processes in the early stage, underscoring the importance of plant selection in recruiting protective microbes for rhizosphere immunity. Our study sheds light on the development of microbiome-based strategies for plant disease management and resistance breeding.

2.
Hematology ; 29(1): 2379597, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39056503

RESUMO

BACKGROUND: Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells. METHODS: Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2. RESULTS: Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells. CONCLUSION: EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Vesículas Extracelulares , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Mesilato de Imatinib/farmacologia , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
3.
Angew Chem Int Ed Engl ; 63(34): e202405131, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-38845566

RESUMO

The limited analgesic efficiency of magnesium restricts its application in pain management. Here, we report boron hydride (BH) with ion currents rectification activity that can enhance the analgesic efficiency of magnesium without the risks of drug tolerance or addiction. We synthesize MgB2, comprising hexagonal boron sheets alternating with Mg2+. In pathological environment, Mg2+ is exchanged by H+, forming two-dimensional borophene-analogue BH sheets. BH interacts with the charged cations via cation-pi interaction, leading to dynamic modulation of sodium and potassium ion currents around neurons. Additionally, released Mg2+ competes Ca2+ to inhibit its influx and neuronal excitation. In vitro cultured dorsal root neurons show a remarkable increase in threshold potential from the normal -35.9 mV to -5.9 mV after the addition of MgB2, indicating potent analgesic effect. In three typical pain models, including CFA-induced inflammatory pain, CINP- or CCI-induced neuropathic pain, MgB2 exhibits analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than clinical MgSO4, respectively, and even about 1.04, 1.66, and 1.95 times higher than morphine, respectively. The development of magnesium based intermetallic compounds holds promise in addressing the non-opioid medical need for pain relief.


Assuntos
Magnésio , Magnésio/química , Animais , Nanoestruturas/química , Camundongos , Analgésicos/química , Analgésicos/farmacologia , Boroidretos/química
4.
Viruses ; 16(3)2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38543818

RESUMO

Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of PoRVA in the world, including China, is of significance for disease prevention. In 2022, a total of 25,768 samples were collected from 230 farms across China, undergoing porcine RVA positivity testing. The results showed that 86.52% of the pig farms tested positive for porcine RVA, with an overall positive rate of 51.15%. Through the genetic evolution analysis of VP7, VP4 and VP6 genes, it was revealed that G9 is the predominant genotype within the VP7 segment, constituting 56.55%. VP4 genotypes were identified as P[13] (42.22%), P[23] (25.56%) and P[7] (22.22%). VP6 exhibited only two genotypes, namely I5 (88.81%) and I1 (11.19%). The prevailing genotype combination for RVA was determined as G9P[23]I5. Additionally, some RVA strains demonstrated significant homology between VP7, VP4 and VP6 genes and human RV strains, indicating the potential for human RV infection in pigs. Based on complete genome sequencing analysis, a special PoRVA strain, CHN/SD/LYXH2/2022/G4P[6]I1, had high homology with human RV strains, revealing genetic reassortment between human and porcine RV strains in vivo. Our data indicate the high prevalence, major genotypes, and cross-species transmission of porcine RVA in China. Therefore, the continuous monitoring of porcine RVA prevalence is essential, providing valuable insights for virus prevention and control, and supporting the development of candidate vaccines against porcine RVA.


Assuntos
Infecções por Rotavirus , Rotavirus , Humanos , Animais , Suínos , Rotavirus/genética , Filogenia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/veterinária , Infecções por Rotavirus/genética , Genoma Viral , Genótipo
5.
Environ Sci Pollut Res Int ; 31(1): 785-802, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38017212

RESUMO

There is a considerable challenge to meeting the Sustainable Development Goals (SDGs) of ending poverty and maintaining ecosystems' function in rural areas, largely due to that the rural people's livelihood relied heavily on fragile ecosystems. China is ambitious to solve this issue by enacting economic stimulus policies such as ecological protection compensation and payment for ecosystem services (ESs). However, these interventions are generally based on stockholders' willingness and lack of scientific basis. Here, we firstly combined InVEST model and social-economic data to evaluate the ecosystem services supply and demand (ESSD), by taking 25 key counties to receive assistance in pursuing rural revitalization in Sichuan province as the study cases. The coupling coordination degree model was then employed to measure the coordination relationship of ESSD. Finally, the driving factors were analyzed based on correlation analysis and stepwise regression method. The results showed that all ESs, except carbon sequestration, were oversupplied with significant spatial heterogeneity. From 2000 to 2020, the supply of all ESs increased, in which the food production had the most notable increase ratio amounting to 48.20%, while the demand of water retention and air purification decreased substantially. Due to the inconsistency between cultivated land area and population changes, significant spatial heterogeneity existed in the coordination relationship of food production. The counties with the highest and the lowest annual average coordination index were Yanyuan (0.9950) and Rangtang (0.1208), respectively. The rural employees and the agricultural gross output value were the key positive factors influencing the quantity and coordination of ESSD, while ecological compensation and financial expenditure had no significant impact, further indicating that these policies were not linked to the performance of ecosystems' function. Finally, policy implications were raised. This study provides a scientific framework for enacting the interventions towards ecological sustainability and poverty ending from ESSD perspective.


Assuntos
Agricultura , Ecossistema , Humanos , Sequestro de Carbono , China , Alimentos , Conservação dos Recursos Naturais
6.
Am J Transl Res ; 15(10): 6189-6198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37969186

RESUMO

PURPOSE: Larger-than-planned capsulotomies can occur, yet their association with age and eye parameters remains poorly understood. This study aimed to assess capsulotomy enlargement after femtosecond laser treatment in cataract surgery and to explore a possible correlation of capsulotomy enlargement with age and eye parameters. METHODS: This retrospective case series included consecutive patients diagnosed with cataracts between 05/2018 and 11/2019. Among them, patients within the age ranges of <18, 18-49, and ≥50 years were assigned to the childhood cataract (CC), young adult cataract (YAC), and age-related cataract (ARC) groups, respectively. The capsulotomy enlargement ratio (CER), age, degree of cataract, lens thickness (LT), axial length, and anterior chamber depth were recorded and analyzed. RESULTS: A total of 155 participants (179 eyes) were enrolled. The CER was significantly different among the three groups (CC: 1.245 vs. YAC: 1.060 vs. ARC: 1.029, P<0.001). The CER was found to be independently associated with both age (ß=-0.011 (0.001), P<0.001) and LT (ß=-0.049 (0.017), P=0.006) in the CC group, but it was only independently correlated with age (ß=-0.004 (0.001), P=0.002) in the YAC group and LT (ß=-0.014 (0.007), P=0.048) in the ARC group. CONCLUSIONS: Capsulotomy enlargement can occur after femtosecond laser treatment in cataract surgery, especially in the non-adult group. Age was a determinant of the CER in CC and YAC groups, while LT was an independent determinant of the CER in CC and ARC groups. These two factors should be taken into consideration for more precise sized capsulotomy.

7.
Chem Biodivers ; 20(12): e202301047, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37577846

RESUMO

Two pairs of new bisabolane-type sesquiterpenoids, (+)-aspersydowin A (7S) [(+)-1], (-)-aspersydowin A (7R) [(-)-1], (+)-aspersydowin B (7S,11S) [(+)-2], (-)-aspersydowin B (7R,11R) [(-)-2], along with six known compounds (1-8) were isolated from the fungus Aspergillus sydowii. Compounds 1 and 2 are enantiomers resolved by the Chiralpak IC, using a hexane- propan-2-ol mobile phase. The structure of 1 and 2 with absolute configuration were assigned tentatively by 1D (1 H, 13 C, and DEPT) & 2D (HSQC, 1 H-1 H COSY, HMBC, and NOESY) NMR data analyses and ECD calculations. Compounds 1-8 were screened for the biological activities in vitro. The results showed that compounds 3, 4 and 8 exhibited immunosuppressive activities with IC50 values of 10.9, 17.6 and 13.4 µM, respectively.


Assuntos
Aspergillus , Sesquiterpenos , Sesquiterpenos Monocíclicos , Estrutura Molecular , Aspergillus/química , Sesquiterpenos/química
8.
Curr Issues Mol Biol ; 45(4): 2832-2846, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37185709

RESUMO

The eggplant (Solanum melongena) is a popular vegetable around the world. However, the origin and evolution of eggplant has long been considered complex and unclear, which has become the barrier to improvements in eggplant breeding. Sequencing and comparative analyses of 13 complete chloroplast (cp) genomes of seven Solanum species were performed. Genome sizes were between 154,942 and 156,004 bp, the smallest genome was from S. torvum and the largest from S. macrocapon. Thirteen cp genomes showed highly conserved sequences and GC contents, particularly at the subgenus level. All genes in the 13 genomes were annotated. The cp genomes in this study comprised 130 genes (i.e., 80 protein-coding genes, 8 rRNA genes, and 42 tRNA genes), apart from S. sisymbriifolium, which had 129 (79 protein-coding genes, 8 rRNA genes, and 42 tRNA genes.). The rps16 was absent from the cp genome of S. sisymbriifolium, resulting in a nonsense mutation. Twelve hotspot regions of the cp genome were identified, which showed a series of sequence variations and differed significantly in the inverted repeat/single-copy boundary regions. Furthermore, phylogenetic analysis was conducted using 46 cp genomic sequences to determine interspecific genetic and phylogenetic relationships in Solanum species. All species formed two branches, one of which contained all cultivars of the subgenus Leptostemonum. The cp genome data and phylogenetic analysis provides molecular evidence revealing the origin and evolutionary relationships of S. melongena and its wild relatives. Our findings suggest precise intra- and interspecies relatedness within the subgenus Leptostemonum, which has positive implications for work on improvements in eggplant breeding, particularly in producing heterosis, expanding the source of species variation, and breeding new varieties.

9.
Org Biomol Chem ; 21(10): 2236-2242, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36815264

RESUMO

Fumitryprostatin A (1), the first example of an indole diketopiperazine alkaloid with a tricyclic 5/6/5 skeleton characterized by a dipyrrolo[1,2-a:1',2'-d]pyrazine-5,10-dione ring system decorated with a prenylated indole moiety, and fuminoid A (2), a sesquiterpenoid with a bicyclo[3.2.1]octane ring featuring a novel carbon skeleton via the transformation of the methyl, were isolated from the fungus Aspergillus fumigatus along with six known diketopiperazine alkaloids. The structure with the absolute configuration of 1 was determined based on spectroscopic analyses and X-ray crystallographic analysis, while the configuration of 2 was assigned tentatively by 13C NMR data with DP4+ probability analyses and ECD calculations. A plausible biosynthetic pathway for 1 was proposed starting from L-Trp and L-Pro via normal indole diketopiperazine. Compound 1 exhibited moderate cytotoxic activity with an IC50 value of 14.6 µM, while compound 8 exhibited moderate immunosuppressive activity in vitro.


Assuntos
Alcaloides , Sesquiterpenos , Aspergillus fumigatus , Sesquiterpenos Monocíclicos , Dicetopiperazinas/farmacologia , Dicetopiperazinas/química , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , Alcaloides/farmacologia , Alcaloides/química , Espectroscopia de Ressonância Magnética , Sesquiterpenos/farmacologia
10.
Food Chem ; 403: 134469, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358102

RESUMO

Radishes are root vegetables that are rich in bioactive compounds and provide numerous health benefits, but the overall metabolic profiles of radish taproots and the metabolic differences among different edible types are not fully understood. In this research, we used UHPLC-Q-TOF-MS to identify the metabolites in cooked, processed and fruit radishes of ten varieties. In total, 264 metabolites belonging to 18 categories were detected. A multivariate analysis revealed that the metabolite composition differed among the three radish groups, and a comparative analysis showed that the significantly differentially accumulated metabolites were mainly amino acids and derivatives, lipids, flavonoids, hydroxycinnamate derivatives and carbohydrates. The accumulation of metabolites, particularly flavonoids, was greater in fruit radishes than in cooked and processed radishes. This work provides novel insights into the radish metabolomic profiles for assessment of the nutritional value of different edible radish types for humans.


Assuntos
Raphanus , Humanos , Raphanus/química , Cromatografia Líquida de Alta Pressão , Metaboloma , Flavonoides/análise , Metabolômica , Suplementos Nutricionais
11.
J Agric Food Chem ; 70(32): 9948-9960, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35917470

RESUMO

Aromatic aldehydes find extensive applications in food, perfume, pharmaceutical, and chemical industries. However, a limited natural enzyme selectivity has become the bottleneck of bioconversion of aromatic aldehydes from natural phenylpropanoid acids. Here, based on the original structure of feruloyl-coenzyme A (CoA) synthetase (FCS) from Streptomyces sp. V-1, we engineered five substrate-binding domains to match specific phenylpropanoid acids. FcsCIAE407A/K483L, FcsMAE407R/I481R/K483R, FcsHAE407K/I481K/K483I, FcsCAE407R/I481R/K483T, and FcsFAE407R/I481K/K483R showed 9.96-, 10.58-, 4.25-, 6.49-, and 8.71-fold enhanced catalytic efficiency for degrading CoA thioesters of cinnamic acid, 4-methoxycinnamic acid, 4-hydroxycinnamic acid, caffeic acid, and ferulic acid, respectively. Molecular dynamics simulation illustrated that novel substrate-binding domains formed strong interaction forces with substrates' methoxy/hydroxyl group and provided hydrophobic/alkaline catalytic surfaces. Five recombinant E. coli with FCS mutants were constructed with the maximum benzaldehyde, p-anisaldehyde, p-hydroxybenzaldehyde, protocatechualdehyde, and vanillin productivity of 6.2 ± 0.3, 5.1 ± 0.23, 4.1 ± 0.25, 7.1 ± 0.3, and 8.7 ± 0.2 mM/h, respectively. Hence, our study provided novel and efficient enzymes for the bioconversion of phenylpropanoid acids into aromatic aldehydes.


Assuntos
Enoil-CoA Hidratase , Escherichia coli , Acil Coenzima A , Aldeídos , Ácidos Cumáricos/química , Enoil-CoA Hidratase/química , Escherichia coli/genética
12.
Adv Mater ; 34(17): e2108653, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35244228

RESUMO

The tumor microenvironment is a complex milieu where neurons constitute an important non-neoplastic cell type. From "cancer neuroscience," the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer-nerve interaction a reciprocally beneficial process. Thus, cancer-nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer-related symptoms. We proposed a nerve-cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered-double-hydroxide nanoshells (Mg/Al-LDH) with AZ-23 loaded inside and alendronate decorated outside. The pain-causing H+ is rapidly eliminated by the LDH, with neurogenesis inhibited by the antagonist AZ-23. As positive feedback, the decreased pain reverses the nerve-to-cancer Ca2+ crosstalk-related cell cycle, dramatically inhibiting tumor growth. All experiments confirm the improved pain threshold and enhanced tumor inhibition. The study may inspire multidisciplinary researchers to focus on cancer-nerve crosstalk for treating cancer and accompanied neuropathic diseases.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Dor do Câncer/tratamento farmacológico , Dor do Câncer/metabolismo , Humanos , Neurônios/metabolismo , Dor/metabolismo , Microambiente Tumoral
13.
ISME Commun ; 2(1): 10, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37938685

RESUMO

The development of strategies for effectively manipulating and engineering beneficial plant-associated microbiomes is a major challenge in microbial ecology. In this sense, the efficacy and potential implications of rhizosphere microbiome transplant (RMT) in plant disease management have only scarcely been explored in the literature. Here, we initially investigated potential differences in rhizosphere microbiomes of 12 Solanaceae eggplant varieties and accessed their level of resistance promoted against bacterial wilt disease caused by the pathogen Ralstonia solanacearum, in a 3-year field trial. We elected 6 resistant microbiomes and further tested the broad feasibility of using RMT from these donor varieties to a susceptible model Solanaceae tomato variety MicroTom. Overall, we found the rhizosphere microbiome of resistant varieties to enrich for distinct and specific bacterial taxa, of which some displayed significant associations with the disease suppression. Quantification of the RMT efficacy using source tracking analysis revealed more than 60% of the donor microbial communities to successfully colonize and establish in the rhizosphere of recipient plants. RTM from distinct resistant donors resulted in different levels of wilt disease suppression, reaching up to 47% of reduction in disease incidence. Last, we provide a culture-dependent validation of potential bacterial taxa associated with antagonistic interactions with the pathogen, thus contributing to a better understanding of the potential mechanism associated with the disease suppression. Our study shows RMT from appropriate resistant donors to be a promising tool to effectively modulate protective microbiomes and promote plant health. Together we advocate for future studies aiming at understanding the ecological processes and mechanisms mediating rates of coalescence between donor and recipient microbiomes in the plant rhizosphere.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1752-1756, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893105

RESUMO

OBJECTIVE: To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients. METHODS: The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR. RESULTS: There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months. CONCLUSION: For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Dasatinibe , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Adulto Jovem
15.
Pharmaceutics ; 13(12)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34959440

RESUMO

Active pharmaceutical ingredients (APIs) extracted and isolated from traditional Chinese medicines (TCMs) are of interest for drug development due to their wide range of biological activities. However, the overwhelming majority of APIs in TCMs (T-APIs), including flavonoids, terpenoids, alkaloids and phenolic acids, are limited by their poor physicochemical and biopharmaceutical properties, such as solubility, dissolution performance, stability and tabletability for drug development. Cocrystallization of these T-APIs with coformers offers unique advantages to modulate physicochemical properties of these drugs without compromising the therapeutic benefits by non-covalent interactions. This review provides a comprehensive overview of current challenges, applications, and future directions of T-API cocrystals, including cocrystal designs, preparation methods, modifications and corresponding mechanisms of physicochemical and biopharmaceutical properties. Moreover, a variety of studies are presented to elucidate the relationship between the crystal structures of cocrystals and their resulting properties, along with the underlying mechanism for such changes. It is believed that a comprehensive understanding of cocrystal engineering could contribute to the development of more bioactive natural compounds into new drugs.

16.
Angew Chem Int Ed Engl ; 60(40): 21905-21910, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34322970

RESUMO

In solid tumors, tumor invasion and metastasis account for 90 % of cancer-related deaths. Cell migration is steered by the lamellipodia formed at the leading edge. These lamellipodia can drive the cell body forward by its mechanical deformation regulated by cofilin. Inhibiting cofilin activity can cause significant defects in directional lamellipodia formation and the locomotory capacity of cell invasion, thus contributing to antimetastatic treatment. Herein, a near infrared light (NIR)-controlled nanoscale proton supplier was designed with upconversion nanoparticles (UCNPs) as a core coated in MIL-88B for interior photoacids loading; this photoacids loading can boost H+ transients in cells, which converts the cofilin to an inactive form. Strikingly, inactive cofilin loses the ability to mediate lamellipodia deformation for cell migration. Additionally, the iron, which serves as a catalyticaly active center in MIL-88B, initiates an enhanced Fenton reaction due to the increased H+ in the tumor, ultimately achieving intensive chemodynamic therapy (CDT). This work provides new insight into H+ transients in cells, which not only regulates cofilin protonation for antimetastatic treatment but also improves chemodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Pseudópodes/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Raios Infravermelhos , Estruturas Metalorgânicas/química , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Propriedades de Superfície
17.
Angew Chem Int Ed Engl ; 60(28): 15472-15481, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33964189

RESUMO

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2- ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2- , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Imidazóis/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Zeolitas/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidazóis/química , Masculino , Estruturas Metalorgânicas/química , Estresse Nitrosativo/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Raios X , Zeolitas/química
18.
Mitochondrial DNA B Resour ; 6(2): 650-652, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33763537

RESUMO

Eggplant is an important vegetable crop because of its rich nutrition, but to date no mitochondrial genome has been reported. In this study, the complete mitochondrial genome of the eggplant was sequenced. The complete mitochondrial genome was 498,136bp, linear structure, containing 54 protein-coding genes, four rRNAs, and 32 tRNAs. The phylogenetic tree supported the hypothesis that the eggplant is most closely related to Solanum tuberosum and Solanum lycopersicum.

19.
Mitochondrial DNA B Resour ; 6(2): 351-357, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33659675

RESUMO

The chloroplast genomic information was obtained from three wild Solanum and four hybrids by chloroplast genome sequencing. The chloroplast genomes of the seven samples comprise of a circular structure and sizes from 155,581 to 155,612 bp and composed of 130 genes. The genome structures of the two hybrids were identical, while the other two hybrids showed 2 bp differences in the LSC when compared with their maternal parent. The total sites of SNP and InDel were 39-344 and 54-90, respectively. With the exception of one hybrid with two additional sites, the other hybrids were identical to their maternal.

20.
Angew Chem Int Ed Engl ; 60(16): 8905-8912, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33527642

RESUMO

The local electron density of an atom is one key factor that determines its chemical properties. Regulating electron density can promote the atom's reactivity and so reduce the reaction activation energy, which is highly desired in many chemical applications. Herein, we report an intra-crystalline electron lever strategy, which can regulate the electron density of reaction centre atoms via manipulating ambient lattice states, for Fenton activity improvement. Typically, with the assistance of ultrasound, the Mn4+ -O-Fe3+ bond in BiFe0.97 Mn0.03 O3 perovskite nanocrystals can drive valence electrons and free electrons to accumulate on Fe atoms by a polarization electric field originated from the designed lattice strain. The increase of electron density significantly improves the catalytic activity of Fe, decreasing the activation energy of BiFe0.97 Mn0.03 O3 -mediated Fenton reaction by 52.55 %, and increasing the . OH yield by 9.21-fold. This study provides a new way to understand the sono-Fenton chemistry, and the increased . OH production enables a highly effective chemodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Compostos de Cálcio/química , Elétrons , Nanopartículas/química , Neoplasias/tratamento farmacológico , Óxidos/química , Terapia Fototérmica , Titânio/química , Antineoplásicos/química , Compostos de Cálcio/metabolismo , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Neoplasias/metabolismo , Óxidos/metabolismo , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Titânio/metabolismo
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