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1.
Biotechnol Lett ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076042

RESUMO

OBJECTIVES: Polymyxins are antibacterial polypeptides used as "last resort" therapy option for multidrug-resistant Gram-negative bacteria. The expansion of polymyxin-resistant infections has inspired development of novel polymyxin derivatives, and deacylation is one of the critical steps in generating those antibiotics. Deacylase from Actinoplanes utahensis hydrolyze the acyl moieties of echinocandins, and also efficiently deacylates daptomycin, ramoplanin and other important antibiotics. Here, deacylase was studied considering its potential usefulness in deacylating polymyxin B1. RESULTS: All the six recombinant strains containing the deacylase gene catalyzed hydrolysis of polymyxin B1, yielding cyclic heptapeptides. The efficiency of recombinant S. albus (SAL701) was higher than that of the others, and deacylation was the most efficient at 40 °C in 0.2 M Tris buffer (pH 8.0) with 0.2 M Mg2+. The optimal substrate concentration of SAL701 was increased from 2.0 to 6.0 g/L. SAL701 was highly thermostable, showing no loss of activity at 50 °C for 12 h, and the mycelia could be recycled at least three times without loss of catalytic activity. SAL701 could not deacylate ß-lactam substrate such as penicillin G and cephalosporin C. Deacylase catalyzes the amide bond 1 closest to the nucleus of polymyxin B1 rather than the other bond, suggesting that it has high catalytic site specificity. Homology modeling and the docking results implied that Thr190 in deacylase could facilitate hydrolysis with high regioselectivity. CONCLUSIONS: These results show that SAL701 is effective in increasing the cyclic heptapeptide moiety of polymyxin B1. These properties of the biocatalyst may enable its development in the industrial production of polymyxins antibiotics.

2.
Nanoscale Adv ; 4(18): 3689-3706, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36133327

RESUMO

Polyoxometalates (POMs), as emerging inorganic metal oxides, have been shown to have significant biological activity and great medicinal value. Nowadays, biologically active POM-based organic-inorganic hybrid materials have become the next generation of antibacterial and anticancer drugs because of their customizable molecular structures related to their highly enhanced antitumor activity and reduced toxicity to healthy cells. In this review, the current developed strategies with POM-based materials for the purpose of antibacterial and anticancer activities from different action principles inducing cell death and hyperpolarization, cell plasma membrane destruction, interference with bacterial respiratory chain and inhibiting bacterial growth are overviewed. Moreover, specific interactions between POM-based materials and biomolecules are highlighted for a better understanding of their antibacterial and anticancer mechanisms. POMs have great promise as next-generation antibacterial and anticancer drugs, and this review will provide a valuable systematic reference for the further development of POM-based nanomaterials.

3.
Front Genet ; 13: 983672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110217

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer in humans globally. In addition to smoking and drinking, genetic and epigenetic changes also play a big role in how HNSCC starts and grows. MicroRNAs are short, non-coding RNAs that control cell differentiation and apoptosis by interfering with gene expression. In addition, microRNAs in HNSCC have been shown to affect the clinical behaviors of HNSCC in amazing ways. Moreover, metabolic reprogramming is a key part of cancer and is needed for cancer to turn into a tumor and grow. But it is still not clear what effect microRNAs related to fatty acid metabolism have on the prognosis of HNSCC patients. We downloaded the data of HNSCC patients from the TCGA database and obtained the genes associated with fatty acid metabolism according to the GSEA database. Then, the microRNAs associated with fatty acid metabolism genes were matched. Finally, fatty acid metabolism gene-associated microRNAs for calculating risk scores and then building multifactorial Cox regression models in patients with HNSCC. Heatmap analysis showed that microRNAs involved in fatty acid metabolism were significantly different in HNSCC patients than in healthy controls. A total of 27 microRNAs associated with fatty acid metabolism were screened by univariate Cox analysis (p < 0.05). Using lasso regression, 18 microRNAs substantially linked with the prognosis of HNSCC patients were identified and included in risk scores. The ROC curves demonstrate that risk scores derived from microRNAs involved in fatty acid metabolism can accurately predict the prognosis of HNSCC patients at 1, 3, and 5 years. Moreover, we discovered that 11 microRNAs included in the risk score properly distinguished the prognosis of HNSCC patients. This paper indicated that microRNAs involved with fatty acid metabolism are strongly linked to the prognosis of HNSCC patients. It also indicated that reprogramming of fatty acid metabolism in tumor tissues may play an important role in HNSCC cancer.

4.
China CDC Wkly ; 4(30): 660-664, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36062070

RESUMO

Introduction: Since first appearing in late 2021, the Omicron variant has spread rapidly around the world. Nevertheless, the XXIV Winter Olympic Games (WOG) were held in Beijing in February 2022, which undoubtedly posed a huge challenge to domestic epidemic prevention and control. Methods: To analyze and evaluate the spread of the epidemic within the closed-loop management of the Beijing 2022 WOG, an improved dynamics model was established. Using the known dynamics parameters, the new daily cases and final members of quarantined people were predicted, and the influence of different factors on the change of the number of quarantined people was analyzed. Results: When the proportion of exposed persons being detected and the degree of admixture between the two populations varied between 0.5 and 0.9, there was little change in the daily predicted number of new cases and the final number of quarantined patients. As the initial value of the exposed among inbound personnel increased, the final size of quarantined patients increased proportionally. Discussion: From the analysis results, detecting potential virus carriers at the entry stage is the most effective way to control the spread of the epidemic within the closed-loop management of the Beijing 2022 WOG.

5.
Plant Cell Rep ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36063182

RESUMO

KEY MESSAGE: Five PeAOX genes from Moso bamboo genome were identified. PeAOX1b_2-OE improved tolerance to drought and salinity stress in Arabidopsis, indicating it is involved in positive regulation of abiotic stress response. Mitochondrial alternative oxidase (AOX), the important respiratory terminal oxidase in organisms, catalyzes the energy wasteful cyanide (CN)-resistant respiration, which can improve abiotic stresses tolerance and is considered as one of the functional markers for plant resistance breeding. Here, a total of five putative AOX genes (PeAOXs) were identified and characterized in a monocotyledonous woody grass Moso bamboo (Phyllostachys edulis). Phylogenetic analysis revealed that PeAOXs belonged to AOX1 subfamily, and were named PeAOX1a_1, PeAOX1a_2, PeAOX1b_1, PeAOX1b_2 and PeAOX1c, respectively. Evolutionary and divergence patterns analysis revealed that the PeAOX, OsAOX, and BdAOX families experienced positive purifying selection and may have undergone a large-scale duplication event roughly 1.35-155.90 million years ago. Additionally, the organ-specific expression analysis showed that 80% of PeAOX members were mainly expressed in leaf. Promoter sequence analysis of PeAOXs revealed cis-acting regulatory elements (CAREs) responding to abiotic stress. Most PeAOX genes were significantly upregulated after methyl jasmonate (MeJA) and abscisic acid (ABA) treatment. Moreover, under salinity and drought stresses, the ectopic overexpression of PeAOX1b_2 in Arabidopsis enhanced seed germination and seedling establishment, increased the total respiratory rate and the proportion of AOX respiratory pathway in leaf, and enhanced antioxidant ability, suggesting that PeAOX1b_2 is crucial for abiotic stress resistance in Moso bamboo.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36098999

RESUMO

We report the bi-polaron transport and magnetic field induced Pauli spin-blockade in solid-state molecular junctions (MJs) evidenced by a positive magnetoresistance (MR). The junction was made of thin layers of redox-active ruthenium polypyridyl-oligomers Ru(tpy) 2 sandwiched between conducting amorphous carbon (a-C) electrodes. The redox-active Ru(tpy) 2 molecule, which enables small polaron and deep traps in the charge transport of the Ru(tpy) 2 MJ as revealed by the temperature-dependent current-voltage response, leads to the formation of the bi-polaron and magnetic field induced Pauli spin blockade, resulting into the MR. At the meantime, the reliable and controllable device performance renders a rigid thickness-dependent MR evolution. The bi-polaron transport revealed in our study underscores the importance of the multi-particle transport by molecular design in MJs and laid the foundation for magnetic-electronic function in molecular-scale devices.

7.
Foods ; 11(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36076775

RESUMO

Betulinic acid (BA) has anti-inflammatory, antioxidative stress, and antitumor activities, but BA bioavailability is low due to its poor water solubility and short half-life. This study aimed to construct a BA delivery system to improve its utilization in vitro. Glycosylated zein (G-zein) was prepared using the wet heating method, and BA-loaded zein composite nanoparticles were prepared using the antisolvent method. Compared to zein, G-zein had the advantages of higher solubility and lower surface hydrophobicity. The encapsulation efficiency of G-zein@BA reached over 80% when the BA concentration was 1 mg/mL. Compared to zein@BA nanoparticles, G-zein@BA was characterized by smaller droplets, higher encapsulation efficiency, and a more stable morphology. The sustained release and solubility of G-zein@BA nanoparticles were also superior to those of zein@BA. Compared with free BA, the dispersions of zein@BA and G-zein@BA nanoparticles in water increased 2.27- and 2.91-fold, respectively. In addition, zein@BA and G-zein@BA nanoparticles markedly inhibited the proliferation of HepG2 cells. This study provides new insights into the structural properties and antitumor activity of BA composite nanoparticles to aid in the development of zein particles as functional materials to deliver bioactive compounds.

8.
Plants (Basel) ; 11(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36079664

RESUMO

Drought affects crop developmentnand growth. To explore the physiological effects of drought stress on soybean, HeiNong44 (HN44) and HeiNong65 (HN65) varieties were used as experimental materials and PEG-6000 was used as the osmotic medium. The antioxidant enzyme activity, osmotic adjustment substance content, antioxidant capacity, and endogenous hormone content of the two soybean varieties were studied under different drought degrees and different treatment durations. Drought stress caused significant physiological changes in soybean. The antioxidant enzyme activities, osmoregulation substance content, and total antioxidant capacity (T-AOC) of HN65 and HN44 showed an increasing trend under mild and moderate drought, however, they first increased and then decreased under severe drought conditions. Following the extension of treatment time, malondialdehyde (MDA) showed an increasing trend. As drought increased, gibberellin (GA) content showed a decreasing trend, while abscisic acid (ABA), salicylic acid (SA), and zeatin nucleoside (ZA) content showed an increasing trend. The auxin (IAA) content of the two varieties showed opposite change trends. In short, drought had a significant impact on the physiology of these two soybean varieties; however, overall, the drought resistance of HN65 was lower than that of HN44. This study provides a research theoretical basis for addressing the drought resistance mechanism and the breeding of drought resistant soybean varieties.

9.
J Enzyme Inhib Med Chem ; 37(1): 2147-2157, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35950567

RESUMO

OBJECTIVE: This work aims to screen drugs for preventing and treating vascular calcification. Method: We screened a series of 3-arylcoumarins for the detection of vascular calcification-associated factors using human aortic vascular smooth muscle cells. RESULTS: We found that compounds 14 and 32 significantly inhibited alkaline phosphatase (ALP) activity similar to aminoguanidine hydrochloride (AGH) in a cellular model of AGEs-induced calcification. We also found that compounds 14 and 32 could significantly decrease the levels of factors such as AGEs, intracellular calcium ions, and total ROS in the calcified cell model. Further study indicates that compound 14 could significantly inhibit the expression of P-ERK1/2, PKC, NF-κB, RAGE and OPN proteins and increased the expression of SM22-α and PPAR-γ proteins in the calcified cells. CONCLUSION: We speculate that compound 14 inhibits vascular calcification by inhibiting oxidative stress and inhibiting AGEs production, suggesting that 3-arylcoumarin derivatives are potential candidates for the treatment of vascular calcification.


Vascular calcification is a process similar to bone formation, which is highly adjustable and active. Currently, there are no specific drugs to delay or reverse vascular calcification. Through the screening of 44 coumarin compounds synthesised by our group, compound 14 was obtained to dose-dependently inhibit the calcification of vascular smooth muscle cells without affecting the normal proliferation of cells, decreasing the intracellular calcium concentration, inhibiting the activity of ALP enzyme. In conclusion, the calcium lowering effect of compound 14 is a potential candidate for drugs for the treatment of vascular calcification.


Assuntos
Cumarínicos/farmacologia , Músculo Liso Vascular , Calcificação Vascular , Células Cultivadas , Humanos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Calcificação Vascular/induzido quimicamente , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/metabolismo
10.
J Ethnopharmacol ; 299: 115652, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36038092

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Mudan decoction (DMD) is a classic prescription for treating intestinal carbuncle from Zhang Zhongjing's "Essentials of the Golden Chamber" in the Han Dynasty. Recent studies also prove that DMD has a therapeutic effect on ulcerative colitis (UC), but its mechanism is still unclear. AIM OF STUDY: In this study, we aim to assess the therapeutic effect of DMD on DSS-induced chronic colitis in mice and deeply expound its underlying regulative mechanism. MATERIALS AND METHODS: The efficacy of DMD on mice with 2% DSS-induced chronic colitis was examined by changes in mouse body weight, DAI score, colon length changes, peripheral blood white blood cells (WBC) and red blood cells (RBC) counts, and hemoglobin (HGB) content, using mesalazine as a positive control. A small animal imaging system observed the FITC-Dextran fluorescence distribution in mice, and the contents of IL-22 and IL-17A in colon tissue homogenate supernatant and LPS in peripheral blood were detected by ELISA. Fluorescence in situ molecular hybridization and bacterial culture were used to investigate bacterial infiltration in intestinal mucosa and bacterial translocation in mesenteric lymph nodes and spleen. Mice immune function was further evaluated by analyzing the changes in spleen index, thymus index, and the ratio of peripheral blood granulocytes, monocytes, and lymphocytes. Meanwhile, the proportion of NCR+ group 3 innate lymphoid cells (ILC3), NCR-ILC3, and IL-22+ILC3 in colonic lamina propria lymphocytes of mice was detected by flow cytometry. The contents of effectors IL-22, IL-17A, and GM-CSF were detected by RT-PCR. We use cell scratching to determine the effect of DMD conditioned medium on the migration of Caco-2 cells by establishing an in vitro model of MNK-3 conditioned medium (CM) intervening Caco-2 cells. RT-PCR and WB detect the expression of tight junction ZO-1, Occludin, and Claudin-1. RESULTS: DMD restored the body weight, colon length, peripheral blood RBC numbers, and HGB content of chronic colitis mice and reduced peripheral blood WBC and colon inflammatory cell infiltration. Moreover, DMD decreased LPS content in serum, bacterial infiltration of colonic mucosa, and bacterial translocation in spleen and mesenteric lymph nodes. Simultaneously, DMD intensified the expression of ZO-1, Occludin, and Claudin-1, the ratio of NCR+ILC3 and IL-22+ILC3, and decreased the proportion of NCR-ILC3. In vitro studies also confirmed that the conditioned medium of DMD promoted the migration of Caco-2 cells and the expression of tight junction proteins. CONCLUSION: Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function.


Assuntos
Colite Ulcerativa , Colite , Animais , Peso Corporal , Células CACO-2 , Claudina-1/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Meios de Cultivo Condicionados/efeitos adversos , Meios de Cultivo Condicionados/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Imunidade Inata , Interleucina-17/metabolismo , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Linfócitos/metabolismo , Mesalamina/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/metabolismo , Proteínas de Junções Íntimas/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-35926777

RESUMO

BACKGROUND & AIMS: Fulminant viral hepatitis (FVH) is a life-threatening disease, but its pathogenesis is not fully understood. Neutrophil extracellular traps (NETs) were an unrecognized link between inflammation and coagulation, which are 2 main features of FVH. Here, we investigated the role and mechanism of NETs in the pathogenesis of FVH. METHODS: A mouse model of FVH was established by murine hepatitis virus strain-3 infection. Liver leukocytes of infected or uninfected mice were used for single-cell RNA sequencing and whole-transcriptome sequencing. NETs depletion was achieved using DNase1. Acetaminophen was used to establish a mouse model of non-virus-caused acute liver failure. Clinically, NETs-related markers in liver, plasma, and peripheral neutrophils were assessed in patients with hepatitis B virus (HBV)-related acute liver injury. RESULTS: Increased hepatic NETs formation was observed in murine hepatitis virus strain-3-infected mice, but not in acetaminophen-treated mice. NETs depletion improved the liver damage and survival rate in FVH by inhibiting hepatic fibrin deposition and inflammation. An adoptive transfer experiment showed that neutrophil-specific fibrinogen-like protein 2 (FGL2) promoted NETs formation. FGL2 was found to directly interact with mucolipin 3, which regulated calcium influx and initiated autophagy, leading to NETs formation. Clinically, increased plasma NETs level was associated with coagulation dysfunction in patients with HBV acute liver injury. Colocalization of FGL2, NETs, and fibrin in liver was observed in these patients. CONCLUSIONS: NETs aggravated liver injury in FVH by promoting fibrin deposition and inflammation. NETs formation was regulated by the FGL2-mucolipin 3-autophagy axis. Targeting NETs may provide a new strategy for the treatment of FVH.

12.
Front Bioeng Biotechnol ; 10: 930800, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992361

RESUMO

The high sensitivity and specificity of terahertz (THz) biosensing are both promising and challenging in DNA sample detection. This study produced and refined a flexible THz MM biosensor for ultrasensitive detection of HBV in clinical serum samples based on a gold magnetic nanoparticle-mediated rolling circle amplification (GMNPs@RCA) sandwich assay under isothermal conditions. Typically, solid-phase RCA reactions mediated by circular padlock probes (PLPs) are triggered under isothermal conditions in the presence of HBV DNA, resulting in long single-stranded DNA (ssDNA) with high fidelity and specificity. Then, the resultant ssDNA was conjugated with detection probes (DPs) immobilized on gold nanoparticles (DP@AuNPs) to form GMNPs-RCA-AuNPs sandwich complexes. The HBV DNA concentrations were quantified by introducing GMNPs-RCA-AuNPs complexes into the metasurface of a flexible THz metamaterial-based biosensor chip and resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 1.27E + 02 IU/ml of HBV DNA from clinical serum samples. The HBV DNA concentration was linearly correlated with the frequency shift of the THz metamaterials within the range of 1.27E + 02∼1.27E + 07 IU/ml, illustrating the applicability and accuracy of our assay in real clinical samples. This strategy constitutes a promising THz sensing method to identify virus DNA. In the future, it is hoped it can assist with pathogen identification and clinical diagnosis.

13.
Cardiol Res Pract ; 2022: 9742071, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032316

RESUMO

Objective: There can be extreme variability between individual responses to exercise training, and the identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We aimed to screen the exercise-related gene sensitivity of patients with acute myocardial infarction after PCI by establishing the gene spectrum of aerobic exercise and cardiopulmonary function sensitivity, test the effect of individualized precision exercise therapy, and provide evidence for the establishment of a precision medicine program for clinical research. Methods: Aerobic exercise- and cardiopulmonary function-related genes and single-nucleotide polymorphisms (SNPs) were obtained by data mining utilizing a major publicly available biomedical repository, the NCBI PubMed database. Biological samples from all participants underwent DNA testing. We performed SNP detection using Samtools. A total of 122 patients who underwent PCI were enrolled in the study. We screened the first 24 cases with a high mutation frequency for aerobic exercise- and cardiopulmonary function-related genes and the last 24 cases with a low mutation frequency and separated them into two groups for the exercise intervention experiment. Results: In both the low mutation frequency group and the high mutation frequency group, after 8 weeks of exercise intervention, 6 MWT distance, 6 MWT%, VO2/kg at peak, and VO2/kg at AT were significantly improved, and the effect in the high mutation frequency group was significantly higher than that in the low mutation frequency group (6 MWT distance: 468 vs. 439, P=0.003; 6 MWT%: 85 vs. 77, P=0.002, VO2/kg at peak: 14.7 vs. 13.3, P=0.002; VO2/kg at AT: 11.9 vs. 13.3, P=0.003). Conclusions: There is extreme variability between individual responses to exercise training. The identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We found that the subjects with a high mutation frequency in aerobic exercise and cardiopulmonary function-related genes achieved more cardiorespiratory fitness benefits in the aerobic exercise rehabilitation program and provided evidence for the establishment of a precision medicine program for clinical research.

14.
Nat Commun ; 13(1): 4647, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941132

RESUMO

While nanoscale quantum emitters are effective tags for measuring biomolecular interactions, their utilities for applications that demand single-unit observations are limited by the requirements for large numerical aperture (NA) objectives, fluorescence intermittency, and poor photon collection efficiency resulted from omnidirectional emission. Here, we report a nearly 3000-fold signal enhancement achieved through multiplicative effects of enhanced excitation, highly directional extraction, quantum efficiency improvement, and blinking suppression through a photonic crystal (PC) surface. The approach achieves single quantum dot (QD) sensitivity with high signal-to-noise ratio, even when using a low-NA lens and an inexpensive optical setup. The blinking suppression capability of the PC improves the QDs on-time from 15% to 85% ameliorating signal intermittency. We developed an assay for cancer-associated miRNA biomarkers with single-molecule resolution, single-base mutation selectivity, and 10-attomolar detection limit. Additionally, we observed differential surface motion trajectories of QDs when their surface attachment stringency is altered by changing a single base in a cancer-specific miRNA sequence.


Assuntos
MicroRNAs , Pontos Quânticos , Piscadela , Óptica e Fotônica , Fótons , Pontos Quânticos/química
15.
Int J Oral Sci ; 14(1): 35, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835750

RESUMO

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.


Assuntos
Cárie Dentária , Criança , Pré-Escolar , Consenso , Cárie Dentária/prevenção & controle , Suscetibilidade à Cárie Dentária , Humanos , Saúde Bucal
16.
Phytochemistry ; 202: 113323, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35835233

RESUMO

One undescribed diterpenoid illisimonone A, four undescribed sesquiterpenes named (±)-simonones A, simonterpenoids A and B, and two undescribed lignans, illisimonins A and B, along with five known compounds were isolated from the fruits of Illicium simonsii. Their structures were elucidated by extensive spectroscopic data. The absolute configuration of illisimonone A was determined by single-crystal X-ray diffraction analysis. Illisimonone A showed potential antiviral activity against the Coxsackie B3 virus, with an IC50 value of 3.70 µM. Illisimonin B and henrylactone A showed potential neuroprotective effects against oxygen-glucose deprivation induced cell injury in SK-N-SH cells, with survival rates of 57.6%, 58.0%, respectively.


Assuntos
Illicium , Fármacos Neuroprotetores , Sesquiterpenos , Antivirais/química , Frutas/química , Illicium/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/química
17.
Cell Rep Med ; 3(7): 100686, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858593

RESUMO

The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/genética , Proteína Adaptadora GRB2 , Fusão Gênica , Humanos , Mutação , Proteínas Oncogênicas , Oncogenes , Feocromocitoma/genética , Proteínas Proto-Oncogênicas c-ret/genética
18.
J Org Chem ; 87(15): 10173-10184, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35877650

RESUMO

An efficient palladium-catalyzed oxidative nonclassical Heck reaction of arylhydrazines with allylic alcohols via C-N bond cleavage has been successfully developed. This method provides a series of ß-arylated carbonyl compounds with broad functional group tolerance under base-free, simple, and mild open air reaction conditions. In the reaction, arylhydrazines with the smaller molecular weight of the leaving group were employed as the "green" arylation reagent, which released N2 and water as the byproducts under air. Mechanistic studies suggested that an aryl radical process and Pd-H complex migration reinsertion were involved. Moreover, the synthesis of the antiarrhythmic drug propafenone was completed with this transformation as the key step.


Assuntos
Estresse Oxidativo , Paládio , Catálise , Estrutura Molecular , Oxirredução , Paládio/química
19.
Angew Chem Int Ed Engl ; 61(39): e202204201, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-35894268

RESUMO

DNA G-quadruplexes (G4s) have been identified as critical elements in modulating genomic functions and many other biological processes. Their functions are highly dependent on the primary nucleotides and secondary folding structures. Therefore, to understand their functions, methods to identify and differentiate structures of G4 with speed and accuracy are required but limited. In this report, we have applied a synthetic G4 DNA-encoded nanoparticle approach to identify and differentiate G4 DNA molecules with different topologies and nucleotide residues. We found that the resulting plasmonic properties of the gold nanoparticles, monitored by UV/Vis spectroscopy, are quite sensitive to different G4 structures, including stacking layers, loop sequences, capping bases on G4s, and topological structures. Through these systematic investigations, we demonstrate that this G4-encoded gold nanoparticle approach can be used to profile the G4 structures and distinguish G4s from human telomeres. Such a method may have wide applications in G4 research.


Assuntos
Quadruplex G , Nanopartículas Metálicas , DNA/química , Ouro , Humanos , Nucleotídeos
20.
Annu Rev Neurosci ; 45: 533-560, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803587

RESUMO

The neocortex is a complex neurobiological system with many interacting regions. How these regions work together to subserve flexible behavior and cognition has become increasingly amenable to rigorous research. Here, I review recent experimental and theoretical work on the modus operandi of a multiregional cortex. These studies revealed several general principles for the neocortical interareal connectivity, low-dimensional macroscopic gradients of biological properties across cortical areas, and a hierarchy of timescales for information processing. Theoretical work suggests testable predictions regarding differential excitation and inhibition along feedforward and feedback pathways in the cortical hierarchy. Furthermore, modeling of distributed working memory and simple decision-making has given rise to a novel mathematical concept, dubbed bifurcation in space, that potentially explains how different cortical areas, with a canonical circuit organization but gradients of biological heterogeneities, are able to subserve their respective (e.g., sensory coding versus executive control) functions in a modularly organized brain.


Assuntos
Neocórtex , Cognição/fisiologia , Função Executiva , Memória de Curto Prazo/fisiologia , Neocórtex/fisiologia , Rede Nervosa/fisiologia
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