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1.
Geospat Health ; 19(1)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619397

RESUMO

Anthrax, a widespread zoonosis in low and middle-income countries with low disease awareness and insufficient livestock vaccination coverage, has been known in Lao Cai Province in northern Vietnam for years before its apparent absence in 2009, which requires investigation as this infection is frequently reported from neighbouring provinces and countries. We aimed to describe the seasonal patterns of anthrax (1991-2008), compare livestock anthrax vaccine coverage to disease occurrence (1991- 2022), and delineate the high-risk areas to inform local disease surveillance in the province. We illustrated the seasonal pattern of anthrax and provided a comparison between livestock vaccine coverage and disease occurrence by purely spatial SaTScan (Poisson model, 25% population at risk) to detect spatial clusters of human and livestock anthrax using population derived from zonal statistics routines. The number of cases, crude cumulative incidence, and spatial clusters of human and livestock anthrax were mapped in QGIS. Results indicate peak anthrax incidence from May to October. Buffalo, domestic cattle, and horses accounted for 75% of total animal cases. Horse anthrax was more common in Lao Cai than in its neighbours and often occurred in years with human mortality. Vaccination covered less than 30% of the livestock population. We found an apparent pattern where anthrax was controlled from 1998-2003 with higher vaccine coverage (>20%) and identified spatial clusters of human and livestock anthrax in Muong Khuong, Bao Thang, and Bac Ha districts of Lao Cai. The local public health and veterinary agencies are recommended to revisit the high-risk areas and communicate with neighbouring provinces for a regional approach to anthrax surveillance and control.


Assuntos
Antraz , Vacinas , Humanos , Bovinos , Animais , Cavalos , Antraz/epidemiologia , Antraz/veterinária , Gado , Laos , Vietnã/epidemiologia
2.
Zookeys ; 1197: 13-41, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38616921

RESUMO

This paper contains descriptions and illustrations of five new species of the genus Aulacocentrum Brues, 1922, from Vietnam, viz. Aulacocentrumassitum Long & Pham, sp. nov.; A.glabrum Long, sp. nov.; A.imparum Long & van Achterberg, sp. nov.; A.intermedium Long & van Achterberg, sp. nov.; and A.simulatum Long, sp. nov. Additionally, Aulacocentrumseticella van Achterberg & He is newly recorded for Vietnam's braconid fauna. A checklist and a key to the Oriental and East Palaearctic Aulacocentrum species is provided and the in-country distribution of the Vietnamese species is given.

3.
Molecules ; 29(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38611738

RESUMO

The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families. Lichenysins (3-7) were isolated from the sub-fraction, which showed significant anti-biofilm activity against Pseudomonas aeruginosa MUC-N1. Their structures were confirmed by detailed 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC, TOCSY, ROESY) recorded in CD3OH, and their absolute configurations were determined using the modified Marfey's method. The isolated lichenysins showed anti-biofilm activity at a minimum concentration of 100 µM. When evaluated for antibacterial activity against a panel of Gram-positive and Gram-negative strains, two isolated lichenysins exhibited selective activity against the MRSA strain without affecting its growth curve and without membranotropic activity. This study highlights the power of the MS/MS spectral similarity strategy using computational methods to obtain a cross-validation of the annotated molecules from the complex metabolic profile of a marine sediment-derived Streptomyces extract. This work provides the first report from a Streptomyces strain of combined cyclic and linear lichenysins and surfactins, known to be characteristic compounds of the genus Bacillus.


Assuntos
Sedimentos Geológicos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , RNA Ribossômico 16S , Vietnã
4.
Science ; 384(6693): 307-312, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38635712

RESUMO

Magnetic skyrmions are topological magnetic textures that hold great promise as nanoscale bits of information in memory and logic devices. Although room-temperature ferromagnetic skyrmions and their current-induced manipulation have been demonstrated, their velocity has been limited to about 100 meters per second. In addition, their dynamics are perturbed by the skyrmion Hall effect, a motion transverse to the current direction caused by the skyrmion topological charge. Here, we show that skyrmions in compensated synthetic antiferromagnets can be moved by current along the current direction at velocities of up to 900 meters per second. This can be explained by the cancellation of the net topological charge leading to a vanishing skyrmion Hall effect. Our results open an important path toward the realization of logic and memory devices based on the fast manipulation of skyrmions in tracks.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38457323

RESUMO

Network compression techniques that combine tensor decompositions and pruning have shown promise in leveraging the advantages of both strategies. In this work, we propose enhanced Network cOmpRession through TensOr decompositions and pruNing (NORTON), a novel method for network compression. NORTON introduces the concept of filter decomposition, enabling a more detailed decomposition of the network while preserving the weight's multidimensional properties. Our method incorporates a novel structured pruning approach, effectively integrating the decomposed model. Through extensive experiments on various architectures, benchmark datasets, and representative vision tasks, we demonstrate the usefulness of our method. NORTON achieves superior results compared to state-of-the-art (SOTA) techniques in terms of complexity and accuracy. Our code is also available for research purposes.

7.
J Invest Dermatol ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38431221

RESUMO

Common capillary malformations are red vascular skin lesions, most commonly associated with somatic activating GNAQ or GNA11 mutations. We focused on capillary malformations lacking such a mutation to identify previously unreported genetic causes. We used targeted next-generation sequencing on 82 lesions. Bioinformatic analysis allowed the identification of 9 somatic pathogenic variants in PIK3R1 and PIK3CA, encoding for the regulatory and catalytic subunits of phosphoinositide 3-kinase, respectively. Recharacterization of these lesions unraveled a common phenotype: a pale capillary malformation associated with visible dilated veins. Primary endothelial cells from 2 PIK3R1-mutated lesions were isolated, and PI3k-Akt-mTOR and RAS-RAF-MAPK signaling were assessed by western blot. This unveiled an abnormal increase in Akt phosphorylation, effectively reduced by PI3K pathway inhibitors, such as mTOR, Akt, and PIK3CA inhibitors. The effects of mutant PIK3R1 were further studied using zebrafish embryos. Endothelium-specific expression of PIK3R1 mutants resulted in abnormal development of the posterior capillary-venous plexus. In summary, capillary malformation associated with visible dilated veins emerges as a clinical entity associated with somatic pathogenic variants in PIK3R1 or PIK3CA (nonhotspot). Our findings suggest that the activated Akt signaling can be effectively reversed by PI3K pathway inhibitors. In addition, the proposed zebrafish model holds promise as a valuable tool for future drug screening aimed at developing patient-tailored treatments.

8.
Sci Rep ; 14(1): 6969, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521815

RESUMO

Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells. The silica-coated fluorescein isothiocyanate isomer (FITC-SiO2) nanoparticles (NPs) were modified with carboxymethylsilanetriol disodium salt (FITC-SiO2-COOH), integrating the dianion form of FITC molecules. This nanosystem exhibited superior dispersion in aqueous solutions and effectively mitigated dye leakage. These labeled NPs displayed notable biocompatibility and minimal cytotoxicity in both in vitro and in vivo conditions. Significantly, the NPs did not have negative implications on cell migration or angiogenesis. They successfully penetrated primary fibroblasts, human umbilical vein endothelial cells and HeLa cells in both 2D and 3D cultures, with the fluorescence signal enduring for over 72 h. Furthermore, the NP signals were consistently observed in the developing gastrointestinal tract of live medaka fish larvae for extended periods during phases of subdued digestive activity, without manifesting any apparent acute toxicity. These results underscore the promising utility of FITC-SiO2-COOH NPs as advanced live cell trackers in biological research.


Assuntos
Nanopartículas , Dióxido de Silício , Animais , Humanos , Células HeLa , Fluoresceína-5-Isotiocianato , Dióxido de Silício/química , Células Endoteliais , Nanopartículas/toxicidade , Nanopartículas/química
9.
Nano Lett ; 24(12): 3557-3565, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38499397

RESUMO

Magnetic skyrmions are topological spin textures which are envisioned as nanometer scale information carriers in magnetic memory and logic devices. The recent demonstrations of room temperature skyrmions and their current induced manipulation in ultrathin films were first steps toward the realization of such devices. However, important challenges remain regarding the electrical detection and the low-power nucleation of skyrmions, which are required for the read and write operations. Here, we demonstrate, using operando magnetic microscopy experiments, the electrical detection of a single magnetic skyrmion in a magnetic tunnel junction (MTJ) and its nucleation and annihilation by gate voltage via voltage control of magnetic anisotropy. The nucleated skyrmion can be manipulated by both gate voltages and external magnetic fields, leading to tunable intermediate resistance states. Our results unambiguously demonstrate the readout and voltage controlled write operations in a single MTJ device, which is a major milestone for low power skyrmion based technologies.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38468535

RESUMO

Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume-Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.

11.
Langmuir ; 40(11): 6051-6064, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38437236

RESUMO

Preconcentration of biomolecules based on ion concentration polarization (ICP) has been splendidly applied to various biomedical and chemical processes. However, in many circumstances, biomolecule preconcentration could not occur due to the lack of full studies on the preconcentration mechanism, especially on the effect of microchannel dimensions. In this work, we provide analytical studies on the critical dimensions (minimum and maximum) of microchannels for the preconcentration of biomolecules. These formulas are verified with the numerical results by fully solving the coupled governing equations: Poisson-Nernst-Planck and Navier-Stokes experiments with appropriate boundary conditions and assumptions. In addition, we examine the impact of operational parameters, such as electric potentials and critical external pressures, on the formation of the preconcentration. Moreover, two important results are provided for the first time, including the position of the preconcentrated biomolecule region and the concentration enhancement factor of the biomolecules. These analytical and numerical results are consistent with experimental observations and, therefore, could provide sharp insight into the mechanism of biomolecule preconcentration and give useful guidelines to better design and optimize ICP-based microfluidic preconcentration devices.


Assuntos
Dispositivos Lab-On-A-Chip
12.
Sci Data ; 11(1): 321, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548727

RESUMO

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.


Assuntos
Broncoscopia , Neoplasias Pulmonares , Humanos , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico por imagem , Tórax/diagnóstico por imagem , Pontos de Referência Anatômicos/diagnóstico por imagem
13.
Analyst ; 149(8): 2252-2271, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38470814

RESUMO

A convergent sector in microfluidic devices utilizing ion concentration polarization (ICP) can help increase the preconcentration rate and the concentration enhancement factor (CEF) of biomolecules. In this work, we present a detailed study of the nozzle-like-squeeze effect of a convergent channel on the preconcentration of biomolecules. By numerically solving coupled Nernst-Planck-Poisson-Navier-Stokes governing equations for the 2D channel model, we report the first study on the critical width of a convergent region in the channel to retain the advantage of the nozzle-like-squeeze effect in speeding up preconcentration and augmenting CEF. In addition, we investigated the impact of the location and the dimensions of a convergent sector on the mechanism of biomolecule preconcentration. The location of an ion-selective membrane was also determined to ensure that biomolecules are focused on the convergent region of the channel. Moreover, we introduce analytical studies to compare and verify simulation findings. Specifically, the formulas for the critical dimensions of a convergent channel, location of a preconcentrated biomolecule plug, and position of an ion-selective membrane are presented. Furthermore, important working parameters, including electric potentials and hydrostatic pressures, were examined to scrutinize their effect on convergent concentrators. These detailed analytical solutions and numerical simulation results are consistent with experimental observations, providing deep insights into the ICP phenomenon and the preconcentration mechanism of biomolecules in convergent microfluidic concentration devices.


Assuntos
Técnicas Analíticas Microfluídicas , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip
14.
Org Biomol Chem ; 22(11): 2307-2312, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38410077

RESUMO

Phytic acid is abundant in various plant-based foods and is considered agricultural waste. Here, we demonstrate the effectiveness of this organophosphorus acid as a sustainable catalyst for the direct amination reactions of allylic alcohols. This approach is successfully performed in air using technical grade solvents, affording allylanilines in moderate to excellent yields. Challenging electron-rich anilines react effectively, and their corresponding Friedel-Crafts side products can be minimised under the optimised reaction conditions. A variety of asymmetrically substituted allylic alcohols are tolerated, while the scope is extended to amide, and C-, O- and S-nucleophiles.

15.
BMC Oral Health ; 24(1): 230, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350906

RESUMO

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.


Assuntos
Periodontite Periapical , Fibrina Rica em Plaquetas , Materiais Restauradores do Canal Radicular , Humanos , Compostos de Cálcio/uso terapêutico , Materiais Restauradores do Canal Radicular/uso terapêutico , Guta-Percha/uso terapêutico , Periodontite Periapical/terapia , Periodontite Periapical/patologia , Combinação de Medicamentos , Ápice Dentário/diagnóstico por imagem , Ápice Dentário/patologia , Óxidos/uso terapêutico , Silicatos/uso terapêutico
16.
BMC Cancer ; 24(1): 176, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317094

RESUMO

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.


Assuntos
Afatinib , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Vietnã/epidemiologia
17.
Heliyon ; 10(2): e24305, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293395

RESUMO

Four imidazolium-based ionic liquids (ILs) with two cations 1-pentyl-3-butylimidazolium [PBIM]+ and 1-benzyl-3-butylimidazolium tetrafluoroborate [BzBIM]+, and two anions tetrafluoroborate (BF4-) and trifluoromethanesulfonate (OTf-) were synthesized for NH3 solubility enhancement. The structural, thermal, and electrochemical stabilities, ionic conductivity, and viscosity of the four ILs, namely, [PBIM]BF4, [BzBIM]BF4, [PBIM]OTf, and [BzBIM]OTf, were investigated. Due to the intermolecular interaction of the benzyl group attached to the imidazolium ring, [BzBIM]+-based ILs exhibited higher thermal stability but lower ionic conductivity compared to [PBIM]+-based ILs. Further, the NH3 solubility in all ILs was measured using a custom-made setup at temperatures ranging from 293.15 to 323.15 K and pressures ranging from 1 to 5 bar. The effects of the cation and anion structures of ILs, as well as pressure and temperature, on the NH3 solubility in the ILs were also investigated. [PBIM]BF4 showed the best solubility because of its high free volume and low viscosity. Density functional calculations validated the superior NH3 solubility in [PBIM]BF4, attributable to the minimal reorganization of the [cation]anion complex geometry during the solvation process, yielding a low solvation free energy. The findings of this study suggest that ILs exhibit a high NH3 solubility capacity and cation and anion structures considerably affect the NH3 solubility in ILs.

18.
Fitoterapia ; 173: 105826, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219842

RESUMO

Five undescribed lignans, cleiseberharnins A-D (1-4), cleiseberharside A (5) were isolated from the fruits of Cleistanthus eberhartii (Phyllanthaceae), together with six known aryltetralin lignans, cleistantoxin (6), picroburseranin (7), neocleistantoxin (8), 7-hydroxypicropolygamain (9), cleisindoside D (10), and cleisindoside A (11). Their structures and relative configurations were established by analysis of HRESIMS and NMR data, and quantum chemical calculations of JH,H coupling constants. The absolute configurations of 1-5 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. All compounds (1-11) were evaluated for their cytotoxicity against KB, MCF-7, HepG-2, and Lu-1 human cancer cell lines. Among the tested compounds, compounds 6 and 7 showed strong activity against KB, MCF7, HepG2 and Lu-1 cell lines with IC50 values in the range of 0.02-0.62 µM. Compound 1 showed activity against three cancer cell lines KB, HepG2, and Lu-1 with IC50 values of 6.98, 7.61 and 11.75 µM, respectively. Compound 2 exhibited a selective inhibition with moderate cytotoxicity against Lu-1 with IC50 value of 15.30 µM. Compounds 4, 5 and 9 showed moderate activity against the three cancer cell lines with IC50 values in the range of 8.73-19.70 µM.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Lignanas , Malpighiales , Humanos , Linhagem Celular Tumoral , Frutas/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Estrutura Molecular , Lignanas/farmacologia , Lignanas/química
19.
ACS Sens ; 9(1): 455-463, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38234004

RESUMO

Selective detection of biomarkers at low concentrations in blood is crucial for the clinical diagnosis of many diseases but remains challenging. In this work, we aimed to develop an ultrasensitive immunoassay that can detect biomarkers in serum with an attomolar limit of detection (LOD). We proposed a sandwich-type heterogeneous immunosensor in a 3 × 3 well array format by integrating a resonant waveguide grating (RWG) substrate with upconversion nanoparticles (UCNPs). UCNPs were used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG substrate, and the RWG substrate was used to enhance the upconversion luminescence (UCL) of UCNPs through excitation resonance. The LOD of the immunosensor was greatly reduced due to the increased UCL of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface by coating the RWG substrate surface with a carboxymethyl dextran layer. The immunosensor exhibited an extremely low LOD [0.24 fg/mL (9.1 aM)] and wide detection range (1 fg/mL to 100 pg/mL) in the detection of cardiac troponin I (cTnI). The cTnI concentrations in human serum samples collected at different times during cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) chemotherapy in a breast cancer patient were measured by an immunosensor, and the results showed that the CEF chemotherapy did cause cardiotoxicity in the patient. Having a higher number of wells in such an array-based biosensor, the sensor can be developed as a high-throughput diagnostic tool for clinically important biomarkers.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Humanos , Troponina I , Imunoensaio/métodos , Nanopartículas/química , Epirubicina , Biomarcadores
20.
Appl Microbiol Biotechnol ; 108(1): 107, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38217253

RESUMO

Streptomyces peucetius ATCC 27952 is known to produce a variety of secondary metabolites, including two important antitumor anthracyclines: daunorubicin and doxorubicin. Identification of peucemycin and 25-hydroxy peucemycin (peucemycin A), as well as their biosynthetic pathway, has expanded its biosynthetic potential. In this study, we isolated a new peucemycin derivative and identified it as 19-hydroxy peucemycin (peucemycin B). Its antibacterial activity was lower than those of peucemycin and peucemycin A. On the other hand, this newly identified peucemycin derivative had higher anticancer activity than the other two compounds for MKN45, NCI-H1650, and MDA-MB-231 cancer cell lines with IC50 values of 76.97 µM, 99.68 µM, and 135.2 µM, respectively. Peucemycin biosynthetic gene cluster revealed the presence of a SARP regulator named PeuR whose role was unknown. The presence of the TTA codon in the peuR and the absence of global regulator BldA in S. peucetius reduced its ability to regulate the peucemycin biosynthetic gene cluster. Hence, different mutants harboring these genes were prepared. S. peucetius bldA25 harboring bldA produced 1.75 times and 1.77 times more peucemycin A (11.8 mg/L) and peucemycin B (21.2 mg/L), respectively, than the wild type. On the other hand, S. peucetius R25 harboring peuR produced 1.86 and 1.79 times more peucemycin A (12.5 mg/L) and peucemycin B (21.5 mg/L), respectively, than the wild type. Finally, strain S. peucetius bldAR25 carrying bldA and peuR produced roughly 3.52 and 2.63 times more peucemycin A (23.8 mg/L) and peucemycin B (31.5 mg/L), respectively, than the wild type. KEY POINTS: • This study identifies a new peucemycin derivative, 19-hydroxy peucemycin (peucemycin B). • The SARP regulator (PeuR) acts as a positive regulator of the peucemycin biosynthetic gene cluster. • The overexpression of peuR and heterologous expression of bldA increase the production of peucemycin derivatives.


Assuntos
Daunorrubicina , Doxorrubicina , Streptomyces , Antraciclinas/metabolismo , Antibióticos Antineoplásicos/farmacologia
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