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1.
Mol Psychiatry ; 29(2): 505-517, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167865

RESUMO

Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, we observe that the K4R variant, associated with reduced PD risk, exhibits increased stability compared to WT SHLP2. Additionally, both WT and K4R SHLP2 show enhanced protection against mitochondrial dysfunction in in vitro experiments and confer protection against a PD-inducing toxin, a mitochondrial complex 1 inhibitor, in a mouse model. This study sheds light on the functional consequences of the m.2158 T > C mtSNP on SHLP2 and provides insights into the potential mechanisms by which this mtSNP may reduce the risk of PD.


Assuntos
Mitocôndrias , Doença de Parkinson , Polimorfismo de Nucleotídeo Único , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Animais , Camundongos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Mitocôndrias/metabolismo , DNA Mitocondrial/genética , Fatores de Proteção , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Modelos Animais de Doenças , Masculino , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/genética , Peptídeos/genética , Peptídeos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular
2.
J Am Chem Soc ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358830

RESUMO

Boranes with closed polyhedral structures feature peculiar bonding and structural characteristics, rendering them widely applicable in diverse research areas ranging from basic functionalization reactions to applications such as medicine, nanomaterials, molecular electronics, and neutron capture therapy. Among the closed borane family, the neutral and cationic heptaborane B7 clusters have been missing in contemporary boron cluster chemistry to date. Herein, we report a polyhedral expansion protocol to construct a neutral derivative of closo-heptaborane (B7) from closo-hexaborane (B6) mediated by borane. Conversion of the neutral derivative of closo-heptaborane to a cationic derivative is also demonstrated. X-ray crystallographic and spectroscopic analyses with the aid of quantum chemical calculations reveal that both neutral and cationic derivatives of closo-heptaborane exhibit a pentagonal-bipyramidal geometry and involve the delocalized σ skeletal electrons, leading to three-dimensional aromaticity. Moreover, the B7 core of the former undergoes a complexation reaction with silver tetrafluoroborate, representing the first experimental demonstration of the nucleophilic nature of the closo-heptaborane.

3.
Inorg Chem ; 63(5): 2745-2755, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38241145

RESUMO

Hematite (α-Fe2O3) photoanode is a promising candidate for efficient PEC solar energy conversion. However, the serious charge recombination together with the sluggish water oxidation kinetics of α-Fe2O3 still restricts its practical application in renewable energy systems. In this work, a CoOOH/α-Fe2O3/SnO2 photoanode was fabricated, in which the ultrathin SnO2 underlayer is deposited on the fluorine-doped tin oxide (FTO) substrate, α-Fe2O3 nanorod array is the absorber layer, and CoOOH nanosheet is the surface modifier, respectively. The resulting CoOOH/α-Fe2O3/SnO2 exhibited excellent PEC water splitting with a high photocurrent density of 2.05 mA cm-2 at 1.23 V vs RHE in the alkaline electrolyte, which is ca. 3.25 times that of bare α-Fe2O3. PEC characterizations demonstrated that SnO2 not only could block hole transport from α-Fe2O3 to FTO substrate but also could efficiently enhance the light-harvesting property and reduce the surface states by controlling the growth process of α-Fe2O3, while the CoOOH overlayer as cocatalysts could rapidly extract the photogenerated holes and provide catalytic active sites for water oxidation. Benefiting from the synergistic effects of SnO2 and CoOOH, the efficiency of the charge recombination and the overpotential for water oxidation of α-Fe2O3 are obviously decreased, resulting in the boosted PEC efficiency for water oxidation. The rational design and simple fabrication strategy display great potentials to be used for other PEC systems with excellent efficiency.

4.
Exp Parasitol ; 260: 108746, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513972

RESUMO

In Dermanyssus gallinae, a hematophagous mite, the initiation of vitellogenesis induced by blood feeding is essential for its reproduction. However, the precise gene structures and physiological functions of Vg in D. gallinae and its upstream gene, Target of Rapamycin (TOR), have not been fully understood. This study revealed the presence of four homologous genes within D. gallinae, named Dg-Vg1, Dg-Vg1-like, Dg-Vg2, and Dg-Vg2-like, especially, Dg-Vg2-like was firstly identified in the mites. The expression levels of all these Vg genes were significantly higher in adult females than other stages. Following blood feeding, the expression levels of these genes increased significantly, followed by a subsequent decrease, aligning with egg production. Silencing Dg-Vgs by RNA interference (RNAi) led to decreased fecundity and egg hatching rates, as well as abnormal embryonic development, suggesting a vital role for Dg-Vgs in both egg formation and embryonic development. Furthermore, the knockdown of Dg-TOR significantly reduced the expression of Dg-Vgs and negatively impacted the reproductive capabilities of PRMs, indicating that TOR influences PRM reproduction by regulating the expression of Dg-Vgs. In summary, these findings demonstrated the crucial roles of Dg-Vgs and Dg-TOR in PRM reproduction, highlighting their potential as targets for pest control.


Assuntos
Ácaros , Interferência de RNA , Reprodução , Serina-Treonina Quinases TOR , Vitelogeninas , Animais , Vitelogeninas/genética , Vitelogeninas/metabolismo , Feminino , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Ácaros/genética , Ácaros/fisiologia , Masculino , Sequência de Aminoácidos , Filogenia , Fertilidade/genética , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Vitelogênese/genética
5.
Pestic Biochem Physiol ; 202: 105960, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879342

RESUMO

Dermanyssus gallinae, a worldwide pest in birds, has developed varying degrees of resistance to insecticides. The ATP-binding cassette (ABC) transporters are essential for the removal of xenobiotics from arthropods. However, our knowledge about ABC transporter proteins in D. gallinae is limited. Forty ABC transporters were identified in the transcriptome and genome of D. gallinae. The resistant population displayed an augmented metabolic rate for beta-cypermethrin compared to the susceptible group, with a remarkable increase in the content of ABC transporters. Verapamil was found able to increase the toxicity of beta-cypermethrin in the resistant population. Results from qRT-PCR analysis showed that eleven ABC transcripts were more highly expressed in the resistant population than the susceptible group at all stages of development, and beta-cypermethrin was observed to be able to induce the expression of DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 in D. gallinae. RNAi-mediated knockdown of the five genes was observed to increase the susceptibility of resistant mites to beta-cypermethrin. These results suggest that ABC transporters, DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 genes, may be related to beta-cypermethrin resistance in D. gallinae. This research will serve as a foundation for further studies on mechanism of insecticide resistance, which could be beneficial for controlling D. gallinae.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Ácaros , Piretrinas , Animais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Piretrinas/farmacologia , Piretrinas/toxicidade , Ácaros/efeitos dos fármacos , Ácaros/genética , Inseticidas/farmacologia , Inseticidas/toxicidade , Aves Domésticas , Resistência a Inseticidas/genética
6.
BMC Genomics ; 24(1): 531, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679709

RESUMO

BACKGROUND: Due to the influence of extreme weather, the environment in China's main cotton-producing areas is prone to drought stress conditions, which affect the growth and development of cotton and lead to a decrease in cotton yield. RESULTS: In this study, 188 upland cotton germplasm resources were phenotyped for data of 8 traits (including 3 major yield traits) under drought conditions in three environments for two consecutive years. Correlation analysis revealed significant positive correlations between the three yield traits. Genetic analysis showed that the estimated heritability of the seed cotton index (SC) under drought conditions was the highest (80.81%), followed by that of boll weight (BW) (80.64%) and the lint cotton index (LC) (70.49%) With genome-wide association study (GWAS) analysis, a total of 75 quantitative trait loci (QTLs) were identified, including two highly credible new QTL hotspots. Three candidate genes (Gh_D09G064400, Gh_D10G261000 and Gh_D10G254000) located in the two new QTL hotspots, QTL51 and QTL55, were highly expressed in the early stage of fiber development and showed significant correlations with SC, LC and BW. The expression of three candidate genes in two extreme materials after drought stress was analyzed by qRT-PCR, and the expression of these two materials in fibers at 15, 20 and 25 DPA. The expression of these three candidate genes was significantly upregulated after drought stress and was significantly higher in drought-tolerant materials than in drought-sensitive materials. In addition, the expression levels of the three candidate genes were higher in the early stage of fiber development (15 DPA), and the expression levels in drought-tolerant germplasm were higher than those in drought-sensitive germplasm. These three candidate genes may play an important role in determining cotton yield under drought conditions. CONCLUSIONS: This study is helpful for understanding the regulatory genes affecting cotton yield under drought conditions and provides germplasm and candidate gene resources for breeding high-yield cotton varieties under these conditions.


Assuntos
Secas , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Melhoramento Vegetal , Gossypium/genética
7.
Hum Mol Genet ; 31(2): 309-319, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34415308

RESUMO

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.


Assuntos
Epigenoma , Genoma Mitocondrial , Idoso , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Epigenoma/genética , Feminino , Genoma Mitocondrial/genética , Humanos , Masculino , Pessoa de Meia-Idade
8.
Small ; 19(5): e2205528, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36446719

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA)-infected skin wounds have caused a variety of diseases and seriously endanger global public health. Therefore, multidimensional strategies are urgently to find antibacterial dressings to combat bacterial infections. Antibacterial hydrogels are considered potential wound dressing, while their clinical translation is limited due to the unpredictable risks and high costs of carrier excipients. it is found that the natural star antibacterial and anti-inflammatory phytochemicals baicalin (BA) and sanguinarine (SAN) can directly self-assemble through non-covalent bonds such as electrostatic attraction, π-π stacking, and hydrogen bonding to form carrier-free binary small molecule hydrogel. In addition, BA-SAN gel exhibited a synergistic inhibitory effect on MRSA. And its plasticity and injectability allowed it to be applied as a wound dressing. Due to the matched physicochemical properties and synergistic therapeutic effects, BA-SAN gel can inhibit bacterial virulence factors, alleviate wound inflammation, promote wound healing, and has good biocompatibility. The current study not only provided an antibacterial hydrogel with clinical value but also opened up new prospects that carrier-free hydrogels can be designed and originated from clinically used small-molecule phytochemicals.


Assuntos
Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Hidrogéis/farmacologia , Cicatrização
9.
Rapid Commun Mass Spectrom ; 37 Suppl 1: e9482, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36718938

RESUMO

Pomegranate seeds are a potential source of bioactive compounds. Nonetheless, most pomegranate seeds are discarded in the food processing industry, likely due to the lack of convincing data on their component analysis. METHODS: To reveal the main chemical constituents of pomegranate seeds, a reliable and sensitive method based on ultra-high-performance supercritical fluid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry (MS) was developed. A time-dependent MSE data acquisition mode was applied to acquire the mass spectrometric data. The chemical constituents were identified by an automatic retrieval of a traditional Chinese medicine library and relevant literature. RESULTS: A total number of 59 compounds, including fatty acids, sterols, vitamins, cerebrosides, phospholipids, flavonoids, phenylpropanoids, and others, were tentatively identified. Their possible fragmentation pathways and characteristic ions were proposed and elucidated. CONCLUSIONS: The findings of this study, along with the developed methodology, could provide a reference for basic research on the pharmacodynamic substances of pomegranate seeds and shed light on their potential nutritional and therapeutic applications in the future.


Assuntos
Cromatografia com Fluido Supercrítico , Medicamentos de Ervas Chinesas , Punica granatum , Espectrometria de Massas por Ionização por Electrospray/métodos , Punica granatum/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Sementes/química
10.
Bioorg Chem ; 131: 106337, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603244

RESUMO

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.


Assuntos
Antibacterianos , Arginina , Desenho de Fármacos , Ácido Glicirretínico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Arginina/biossíntese , Escherichia coli/efeitos dos fármacos , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo
11.
Exp Parasitol ; 249: 108530, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37040857

RESUMO

The lifecycle of poultry red mite (PRM), Dermanyssus gallinae,includes several stages and only the adult has been reported to have sex discrimination based on body structures and color patterns. Currently, it's still unknown how to distinguish two sexes of deutonymphs. We measured body length of 254 engorged deutonymphs and examined body size and shape variation of 104 engorged deutonymphs using geometric morphometric techniques. Our findings showed that deutonymph females (with average values of 813.08 µm) had a longer body length than deutonymph males (713.39 µm). Additionally, deutonymph females were found to had a narrow and elongated posterior body shape while deutonymph males had a suboval shape, and the former was bigger than the latter. These results suggest that there is sexual dimorphism in PRM deutonymphs, and the differentiation of deutonymph females and males based on their body length, shape, and size will facilitate a better understanding of reproductive behavior and the accurate population dynamics of PRMs.


Assuntos
Infestações por Ácaros , Ácaros , Doenças das Aves Domésticas , Animais , Feminino , Masculino , Caracteres Sexuais , Estágios do Ciclo de Vida , Galinhas , Infestações por Ácaros/veterinária
12.
Parasitology ; 149(12): 1623-1630, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35993334

RESUMO

The poultry red mite (PRM), Dermanyssus gallinae, is one of the most detrimental ectoparasite on poultry farms worldwide. The blood fed on birds provides the mites with nutrition and energy for their activities, development and reproduction. In the evaluation of the efficacy of novel drugs or vaccines against PRMs, their effects on blood digestion are generally used as a key parameter. The blood digestion of haematophagous arthropods (including D. gallinae) is usually assessed by weighing; however, this method shows some limitations. The main objective of the present study was to develop a scoring method that can quickly and visually evaluate the blood digestion status of PRMs. A 0­4 point scoring criterion was established to describe the blood digestion status of D. gallinae based on the changes in appearance in the intestinal tract of PRMs during the blood digestion process. There was a good consistency between the results obtained by the blood digestion scoring and the weighing, indicating the reliability of this new method. The results obtained from volunteers were consistent with the results from researchers with low coefficient of variation, indicating that the scoring method has good practicability. The applicability of the scoring method was confirmed in an efficacy study, where it was found that doramectin could significantly inhibit the blood digestion of PRMs, lowering the blood digestion score.


Assuntos
Infestações por Ácaros , Ácaros , Doenças das Aves Domésticas , Animais , Humanos , Infestações por Ácaros/prevenção & controle , Infestações por Ácaros/veterinária , Infestações por Ácaros/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/parasitologia , Aves Domésticas , Galinhas/parasitologia , Projetos de Pesquisa , Reprodutibilidade dos Testes , Digestão
13.
Bioorg Chem ; 128: 106066, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35964500

RESUMO

Podophyllotoxin's undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids' moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066-0.831 µM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319-41.080 µM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230-0.745 µM). Moreover, structure-activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 µM) than MDCK cell lines (IC50 = 4.780 ± 0.50 µM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.


Assuntos
Antineoplásicos , Neoplasias , Animais , Antineoplásicos/farmacologia , Apoptose , Ácidos e Sais Biliares/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo/farmacologia , Glucosídeos/farmacologia , Humanos , Camundongos , Estrutura Molecular , Podofilotoxina , Relação Estrutura-Atividade
14.
J Nanobiotechnology ; 20(1): 527, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510210

RESUMO

Through the self-assembled strategy to improve the clinical efficacy of the existing drugs is the focus of current research. Herbal formula granule is a kind of modern dosage form of traditional Chinese medicine (TCM) which has sprung up in recent decades. However, whether it is equivalent to the TCM decoction that has been used for thousands of years has always been a controversial issue. In this paper, taking the herb pair of Coptidis Rhizoma-Scutellariae Radix and its main component berberine-baicalin as examples, the differences and mechanisms of self-assemblies originated from the co-decoction and physical mixture were studied, respectively. Moreover, the relationship between the morphology and antibacterial effects of self-assemblies was illuminated via multi-technology. Our study revealed that the physical mixture's morphology of both the herb pair and the phytochemicals was nanofibers (NFs), while their co-decoction's morphology was nanospheres (NPs). We also found that the antibacterial activity was enhanced with the change of self-assemblies' morphology after the driving by thermal energy. This might be attributed to that NPs could influence amino acid biosynthesis and metabolism in bacteria. Current study provides a basis that co-decoction maybe beneficial to enhance activity and reasonable use of herbal formula granule in clinic.


Assuntos
Berberina , Medicamentos de Ervas Chinesas , Humanos , Antibacterianos/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa
15.
J Nanobiotechnology ; 20(1): 116, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248067

RESUMO

BACKGROUND: Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers. RESULT: In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model. CONCLUSION: This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy.


Assuntos
Produtos Biológicos , Diabetes Mellitus Experimental , Nanopartículas , Administração Oral , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Insulina , Nanopartículas/química , Ratos , Junções Íntimas
16.
Exp Parasitol ; 243: 108422, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36372092

RESUMO

The poultry red mite (PRM) is a detrimental blood-feeding ectoparasite infesting poultry and sylvatic birds. A traditional rearing system of PRMs was usually established by using chickens as the host. However, the system with chickens had some defects, such as high feed consumption, large amount of feces, high cost, and intensive labor. In present study, we used quails as the host to rear mites, and compared the reproductive efficiency of this new system with that of the chicken system. The results showed that the number of mites increased 96-fold and the number of eggs increased 50-fold after four weeks in the quail system, which were significantly higher than those in the system with chickens. The survival rates of mites in both systems were higher than 95%, and the value in the quail system at the fourth week was significantly better than that of the chicken system. The statistical results of feed consumption, live weight, and daily excrement of chickens and quails showed that the quail system was more stable with less feed consumption and less waste excretion than the chicken system. Comparing the number of eggs laid by each female mite, hatching rates and molting rates in both systems, we can conclude that the breeding system, in which quails replaced chickens as hosts, had no effect on the fecundity of D. gallinae. In conclusion, the new system established using quails as the host, is a highly efficient alternative for largely rearing of mites under laboratory conditions.


Assuntos
Infestações por Ácaros , Ácaros , Doenças das Aves Domésticas , Animais , Feminino , Infestações por Ácaros/veterinária , Galinhas/parasitologia , Doenças das Aves Domésticas/parasitologia , Coturnix , Codorniz
17.
Exp Parasitol ; 238: 108230, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35151652

RESUMO

Resistance of Haemonchus contortus to ivermectin has become an increasingly serious problem worldwide. Drug-based control and management of this parasite requires reliable methods for testing drug resistance to evaluate and monitor their anthelmintic effects. In this study, the larval migration inhibition test (LMIT) and the larval feeding inhibition test (LFIT) were used to assess and compare seven strains of H. contortus, including one resistant and one susceptible strain from abroad (UKR and ASS, respectively), and five strains native to China (SXS, WMR, WSR1, WSR2, and WSR3). LFIT results showed that fluorescent-labeled Escherichia coli could be clearly observed after ivermectin (IVM) treatment inside UKR, WMR, WSR1, WSR2, and WSR3 larvae, but not inside ASS and SXS strains. Moreover, LMIT results showed that migration of SXS strain did not change significantly after IVM treatment compared with the susceptible ASS strain, whereas migration increased significantly in the UKR, WMR, WSR1, WSR2, and WSR3 strains. Taken together, SXS was found to be an IVM-susceptible strain, whereas WMR, WSR1, WSR2, and WSR3 were IVM-resistant strains. These results demonstrate that assessment of the motility and feeding ability of H. contortus larvae can be effectively used to determine resistance of H. contortus to IVM.


Assuntos
Anti-Helmínticos , Hemoncose , Haemonchus , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Larva , Ovinos , Doenças dos Ovinos/parasitologia
18.
Proc Natl Acad Sci U S A ; 116(36): 17654-17658, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31427529

RESUMO

The chemistry of d-block metal-metal multiple bonds has been extensively investigated in the past 5 decades. However, the synthesis and characterization of species with f-block metal-metal multiple bonds are significantly more challenging and such species remain extremely rare. Here, we report the identification of a uranium-rhodium triple bond in a heterometallic cluster, which was synthesized under routine conditions. The uranium-rhodium triple-bond length of 2.31 Å in this cluster is only 3% longer than the sum of the covalent triple-bond radii of uranium and rhodium (2.24 Å). Computational studies reveal that the nature of this uranium-rhodium triple bond is 1 covalent bond with 2 rhodium-to-uranium dative bonds. This heterometallic cluster represents a species with f-block metal-metal triple bond structurally authenticated by X-ray diffraction. These studies not only demonstrate the authenticity of the uranium-metal triple bond, but also provide a possibility for the synthesis of other f-block metal-metal multiple bonds. We expect that this work may further our understanding of the bonding between uranium and transition metals, which may help to design new d-f heterometallic catalysts with uranium-metal bonds for small-molecule activation and to promote the utilization of abundant depleted uranium resources.

19.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6066-6075, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471931

RESUMO

The present study aimed to explore the material basis of Rhei Radix et Rhizoma-Coptidis Rhizoma combination in alleviating "bitter-cold" properties based on the supramolecular chemistry of Chinese medicine.Dynamic light scattering and scanning/transmission electron microscopy were used to characterize the morphological characteristics of supramolecules in the decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma.The chemical composition of supramolecules, as well as the dissolution and release processes of supramolecules and the medicinal components of Coptidis Rhizoma decoction, was determined by the high-performance liquid chromatography-mass spectrometry.The differences in "bitter-cold" medicinal properties between Rhei Radix et Rhizoma decoction, Coptidis Rhizoma decoction, and co-decoction were analyzed by sensory evaluation, electronic tongue, mouse diarrhea model, and pathological indicators.The anthraquinones/tannins and alkaloids interacted to form supramolecules with a scale of about 400 nm when Rhei Radix et Rhizoma and Coptidis Rhizoma were decocted together, which delayed the dissolution and release of the active components represented by berberine. Compared with the consequence of single drug administration at 4 g·kg~(-1), the combination of the two drugs at 8 g·kg~(-1) significantly alleviated the "bitter-cold" properties.The effective components interacted to form supramolecules in the co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma, which affected the dissolution and release of the effective components of Chinese medicinal decoction, thereby alleviating the "bitter-cold" properties.The findings of this study provide a new idea for revealing the scientific compatibility of Rhei Radix et Rhizoma and Coptidis Rhizoma.


Assuntos
Antineoplásicos , Medicamentos de Ervas Chinesas , Camundongos , Animais , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Rizoma/química , Antraquinonas/análise , Cromatografia Líquida de Alta Pressão/métodos
20.
Angew Chem Int Ed Engl ; 61(45): e202209438, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36102181

RESUMO

Herein, we report the structures of chiral-at-cage carborane derivatives bearing carbazole chromophores that emit circularly polarized luminescence (CPL) and aggregation-induced electrochemiluminescence (AIECL). By adjusting the substituent positions on the carborane derivatives, two chiral luminescent molecules, Cb1 and Cb2, with different properties were obtained. The photoluminescence dissymmetry factors |gPL | of both (R/S)-Cb1 and (R/S)-Cb2 enantiomers in neat films were as high as 6.24×10-3 and 7.38×10-3 , respectively. Cb1 showed a deep blue emission peak at 434 nm in n-pentane. Interestingly, distinct fluorescence and CPL spectra were observed in solvents of different polarities due to the twisted intramolecular charge transfer effect, suggesting its potential use in solvent recognition. Meanwhile, Cb2 exhibited good AIECL property, excellent ECL stability and could be used for determining dopamine concentrations, suggesting its potential applications in biology and diagnosis.


Assuntos
Luminescência , Medições Luminescentes , Estereoisomerismo
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