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1.
BMC Neurol ; 24(1): 336, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256704

RESUMO

BACKGROUND: The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. METHODS: A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. RESULTS: During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p < 0.01), coefficient of variation (CV) of velocity and stride length (p < 0.05), as well as phase coordination index (PCI) when compared with the low-risk group (p < 0.05). Notably, differences in basic gait parameters were observed in cognitive DTW and STW conditions between the two groups (p < 0.01). However, only the high-risk group evinced significant variations in CV and PCI during cognitive DTW, as opposed to those during STW (p < 0.05). Furthermore, our findings also revealed the association of OF, the gait characteristics of cognitive DTW, (p < 0.01) and falls (p < 0.05). CONCLUSION: CSVD patients with a high risk of OF need to pay more attention to their gait variability or coordination. Also, they are recommended to undergo training involving dual-task activities while walking in daily life, thereby reducing the deterioration and mitigating the risk of falls. Besides, this study has confirmed an association of OF and DTW gait as well as falls in patients with CSVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Fragilidade , Marcha , Humanos , Masculino , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Feminino , Idoso , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Marcha/fisiologia , Acidentes por Quedas/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/epidemiologia , Transtornos Neurológicos da Marcha/etiologia , Caminhada/fisiologia
2.
Diabetes Res Clin Pract ; 217: 111848, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243867

RESUMO

AIMS: Pregnancies are increasingly affected by young-onset type 2 diabetes mellitus (YT2DM), an aggressive phenotype associated with a higher vascular risk profile compared to type 1 diabetes mellitus (T1DM). We compared pregnancy outcomes to illuminate areas where differing management guidance might be needed. METHODS: This retrospective single-centre study (2010 2019) included 259 singleton pregnancies affected by pregestational T1DM (N = 124) or YT2DM (N = 135) diagnosed at < 40 years. Primary outcomes included preterm delivery, large for gestational age (LGA) infants, and pre-eclampsia. RESULTS: The YT2DM cohort were older, with more obesity, greater apparent sociodemographic disadvantage, and lower measures of pregnancy preparedness. Overweight/obesity were also prevalent in the T1DM cohort (46 % affected). The second/third trimester mean HbA1c measurements were significantly higher in the T1DM cohort. Pre-eclampsia and preterm delivery rates were similar between the cohorts. Significantly lower rates of LGA infants, NICU admission, neonatal hypoglycaemia, and neonatal respiratory distress were seen in the YT2DM cohort (p < 0.05 for all). CONCLUSIONS: In pregnancy, YT2DM appears to be the lower-risk cohort compared to T1DM despite higher obesity rates. Gaps in achieving glycaemic targets exist for both subtypes but particularly for T1DM. The relative impact of increasing BMI in pregnancies affected by T1DM requires further elucidation.

3.
Chin J Integr Med ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39240290

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.

4.
Nat Prod Rep ; 41(9): 1457, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39149831

RESUMO

Retraction of 'Recent advances in total synthesis of protoberberine and chiral tetrahydroberberine alkaloids' by Zhen-Xi Niu et al., Nat. Prod. Rep., 2024, https://doi.org/10.1039/d4np00016a.

5.
Trends Pharmacol Sci ; 45(8): 739-756, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39003157

RESUMO

PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death. Given the physiological relevance in several diseases, PANoptosis is a pivotal therapeutic target. Notably, previous research has primarily focused on the role of PANoptosis in cancer and infectious and inflammatory diseases. By contrast, its role in cardiovascular diseases has not been comprehensively discussed. Here, we review the available evidence on PANoptosis in cardiovascular diseases, including cardiomyopathy, atherosclerosis, myocardial infarction, myocarditis, and aortic aneurysm and dissection, and explore a variety of agents that target PANoptosis, with the overarching goal of providing a novel complementary approach to combatting cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Animais , Necroptose , Imunidade Inata
6.
Clin Diabetes Endocrinol ; 10(1): 17, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853254

RESUMO

BACKGROUND: Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in young onset type 2 diabetes mellitus. Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism. BKD typically manifests in childhood as recurrent episodes of ketoacidosis, the frequency of which tends to reduce with age. There is a paucity of data with respect to the co-existence of persistent dysglycemia with BKD. CASE PRESENTATION AND LITERATURE REVIEW: We present a novel case of diabetes presenting as diabetic ketoacidosis in a 34-year-old man with BKD, with genetically confirmed compound heterozygosity for variants in ACAT1, including a novel ACAT1 c.481T>C, p.(Tyr161His) variant. Diabetes in people with BKD presents unique diagnostic and management challenges. To further contextualize our findings, we conducted a comprehensive narrative review of the existing literature with respect to dysglycemia in those with BKD, especially in adulthood. There are no existing reports describing diabetes in adults with BKD. Stress hyperglycemia is not uncommon when children with BKD are acutely unwell, with several pediatric case reports describing short-lived hyperglycemia but normal HbA1c measurements during metabolic crises (indicating the absence of persistent hyperglycemia). CONCLUSIONS: This is the first report of diabetic ketoacidosis in an adult with BKD, with an elevated HbA1c consistent with persistent hyperglycemia. This case highlights the importance of checking HbA1c in people with BKD and hyperglycemia in order to uncover potential coexisting diabetes, facilitating timely management and preventing complications. Increased reporting on the longitudinal outcomes of those with rare metabolic disorders is essential for identifying potential associations with conditions like diabetes.

7.
Nat Prod Rep ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712365

RESUMO

Covering: Up to 2024Due to the widespread distribution of protoberberine alkaloids (PBs) and tetrahydroberberine alkaloids (THPBs) in nature, coupled with their myriad unique physiological activities, they have garnered considerable attention from medical practitioners. Over the past few decades, synthetic chemists have devised various total synthesis methods to attain these structures, continually expanding reaction pathways to achieve more efficient synthetic strategies. Simultaneously, the chiral construction of THPBs has become a focal point. In this comprehensive review, we categorically summarized the developmental trajectory of the total synthesis of these alkaloids based on the core closure strategies of protoberberine and tetrahydroberberine.

8.
Anal Chim Acta ; 1310: 342723, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811138

RESUMO

BACKGROUND: Eugenol compounds (EUGs), which share chemical similarities with eugenol, belong to a group of phenolic compounds primarily found in clove oil. They are highly valued by fish dealers due to their exceptional anesthetic properties, playing a crucial role in reducing disease incidence and mortality during the transportation of live fish. Despite their widespread use, the safety of EUGs remains a contentious topic, raising concerns about the safety of aquatic products. This underscores the need for efficient and sensitive analytical methods for detecting EUGs. RESULTS: Nanomaterial-based ratiometric fluorescence immunoassay has gained increasing attention due to its integration of the immunoassay's excellent specificity and compatibility for high-throughput analysis, coupled with the exceptional sensitivity and anti-interference capabilities of ratiometric fluorescence assays. In this study, we developed a sensitive ratiometric fluorescence immunoassay for screening five EUGs. This method employs a broad-specificity monoclonal antibody (mAb) as a recognition reagent, selective for five EUGs. It leverages the horseradish peroxidase (HRP)-triggered formation of fluorescent 2,3-diaminophenazine (DAP) and the quenching of fluorescent gold clusters (Au NCs) for detection. The assay's detection limits for eugenol, isoeugenol, eugenol methyl eugenol, methyl isoeugenol, and acetyl isoeugenol in tilapia fish and shrimp were found to be 9.8/19.5 µg/kg, 0.11/0.22 µg/kg, 19/36 Tilapia ng/kg, 8/16 ng/kg, and 3.0/6.1 µg/kg, respectively. Furthermore, when testing spiked Tilapia fish and shrimp samples, recoveries ranging from 84.1 to 111.9 %, with the coefficients of variation staying below 7.1 % was achieved. SIGNIFICANCE: This work introduces an easy-to-use, broad-specificity, and highly sensitive method for the screening of five EUGs at a pg/mL level, which not only provides a high-throughput strategy for screening eugenol-type fish anesthetics in aquatic products, but also can serve as a benchmark for developing immunoassays for other small molecular pollutants, rendering potent technological support for guarding food safety and human health.


Assuntos
Eugenol , Ouro , Nanopartículas Metálicas , Eugenol/análise , Eugenol/análogos & derivados , Eugenol/química , Ouro/química , Nanopartículas Metálicas/química , Animais , Imunoensaio/métodos , Limite de Detecção
9.
PLoS One ; 19(4): e0300277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38687723

RESUMO

Apocynum venetum L. belongs to the Apocynaceae family and is a plant that is highly resistant to stress. It is important in the fields of ecology, feeding, industry and medicine. The molecular mechanism underlying salt tolerance has not been elucidated. In this study, RNA-seq based transcriptome sequencing of A. venetum leaves after 0, 2, 6, 12, 24 and 48 h of treatment with 300 mM NaCl was performed. We conducted a comprehensive analysis of the transcriptome expression profiles of A. venetum under salt stress using the WGCNA method and identified red, black, and brown as the core modules regulating the salt tolerance of A. venetum. A co-expression regulatory network was constructed to identify the core genes in the module according to the correlations between genes. The genes TRINITY_DN102_c0_g1 (serine carboxypeptidase), TRINITY_DN3073_c0_g1 (SOS signaling pathway) and TRINITY_DN6732_c0_g1 (heat shock transcription factor) in the red module were determined to be the core genes. Two core genes in the black module, TRINITY_DN9926_c0_g1 and TRINITY_DN7962_c0_g1, are pioneer candidate salt tolerance-associated genes in A. venetum. The genes in the brown module were mainly enriched in two pathways, namely photosynthesis and osmotic balance. Among them, the TRINITY_DN6321_c0_g2 and TRINITY_DN244_c0_g1 genes encode aquaporin, which is helpful for maintaining the cell water balance and plays a protective role in defending A. venetum under abiotic stress. Our findings contribute to the identification of core genes involved in the response of A. venetum to salt stress.


Assuntos
Apocynum , Regulação da Expressão Gênica de Plantas , Estresse Salino , Transcriptoma , Apocynum/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Salino/genética , Redes Reguladoras de Genes/efeitos dos fármacos , Perfilação da Expressão Gênica , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Folhas de Planta/genética
10.
Eur J Med Chem ; 271: 116446, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38678824

RESUMO

The strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular mechanisms. It further outlines the specific effects of fluorination, which contribute to the heightened efficacy of anti-infective therapies. By presenting a comprehensive analysis of current drugs and their developmental pathways, this review underscores the continuing evolution and significance of fluorine in advancing anti-infectious treatment options. The insights offered extend valuable guidance for future drug design and the development of next-generation anti-infectious agents.


Assuntos
Flúor , Flúor/química , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Indústria Farmacêutica , Estrutura Molecular , Animais
11.
Molecules ; 29(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38611934

RESUMO

Spirotryprostatin alkaloids, a class of alkaloids with a unique spirocyclic indoledionepiperazine structure, were first extracted from the fermentation broth of Aspergillus fumigatus and have garnered significant attention in the fields of biology and pharmacology. The investigation into the pharmacological potential of this class of alkaloids has unveiled promising applications in drug discovery and development. Notably, certain spirotryprostatin alkaloids have demonstrated remarkable anti-cancer activity, positioning them as potential candidates for anti-tumor drug development. In recent years, organic synthetic chemists have dedicated efforts to devise efficient and viable strategies for the total synthesis of spirotryprostatin alkaloids, aiming to meet the demands within the pharmaceutical domain. The construction of the spiro-C atom within the spirotryprostatin scaffold and the chirality control at the spiro atomic center emerge as pivotal aspects in the synthesis of these compounds. This review categorically delineates the synthesis of spirotryprostatin alkaloids based on the formation mechanism of the spiro-C atom.


Assuntos
Alcaloides , Fermentação , Aspergillus fumigatus , Descoberta de Drogas
12.
Food Chem X ; 22: 101255, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38444558

RESUMO

In this study, three eugenol fragment-containing haptens were synthesized, and a monoclonal antibody (mAb) selective for five commonly-found eugenol compounds (EUGs, i.e., eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, and acetyl isoeugenol) was obtained. Based on this mAb, a broad-spectrum indirect competitive ELISA for high-throughput detection of five EUGs was developed. The detection limits for eugenol, isoeugenol, methyl eugenol, methyl isoeugenol and acetyl isoeugenol in both tilapia and shrimp samples were 25.3/ 50.6 µg/kg, 0.075/0.15 µg/kg, 0.48/0.96 µg/kg, 0.16/0.32 µg/kg, and 18.16/36.32 µg/kg, respectively. The recoveries for five EUGs ranged from 80.4 to 114.0 % with a coefficient of variation less than 11.5 %. Moreover, homology modelling and molecular docking were conducted to elucidate the interactions mechanism of mAb-EUGs. The work provides a promising tool for high-throughput screening of EUGs in aquatic products, which can serve as a benchmark for designing haptens and developing immunoassays for other small molecules.

13.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474678

RESUMO

Breast cancer, characterized by its molecular intricacy, has witnessed a surge in targeted therapeutics owing to the rise of small-molecule drugs. These entities, derived from cutting-edge synthetic routes, often encompassing multistage reactions and chiral synthesis, target a spectrum of oncogenic pathways. Their mechanisms of action range from modulating hormone receptor signaling and inhibiting kinase activity, to impeding DNA damage repair mechanisms. Clinical applications of these drugs have resulted in enhanced patient survival rates, reduction in disease recurrence, and improved overall therapeutic indices. Notably, certain molecules have showcased efficacy in drug-resistant breast cancer phenotypes, highlighting their potential in addressing treatment challenges. The evolution and approval of small-molecule drugs have ushered in a new era for breast cancer therapeutics. Their tailored synthetic pathways and defined mechanisms of action have augmented the precision and efficacy of treatment regimens, paving the way for improved patient outcomes in the face of this pervasive malignancy. The present review embarks on a detailed exploration of small-molecule drugs that have secured regulatory approval for breast cancer treatment, emphasizing their clinical applications, synthetic pathways, and distinct mechanisms of action.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia , Transdução de Sinais
14.
Phys Chem Chem Phys ; 26(1): 365-372, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38073482

RESUMO

Tungstates with a molecular formula A2W3O12 exhibits a wider negative thermal expansion (NTE) temperature range than molybdates but are challenging to synthesize, especially when A = Fe or Cr with metastable structures. To enhance the structural stability of Fe2W3O12, Sc with lower electronegativity is adopted to substitute Fe according to Fe2-xScxW3O12, considering the thermodynamic stability of Sc2W3O12. It is shown that the solid solutions can be easily synthesized and the phase transition temperature (PTT) can be tuned to well below room temperature (RT). Theoretical calculations and experimental results show that the formation energy decreases and the W-O bond in Fe-O-W gradually strengthens as the substitution of Sc in Fe2-xScxW3O12 increases, indicating an increase in structural stability. NTE is enhanced after phase transition with an increase in the Sc content. The reduction in PTT and the enhancement in NTE properties of Fe2W3O12 could result in a decrease in the effective electronegativity of the Fe-site elements, resulting in a low formation energy and strengthened W-O bond in Fe-O-W, which corresponds to a more stable structure.

15.
Eur J Med Chem ; 262: 115919, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37922830

RESUMO

Hepatitis, a global public health concern, presents a significant burden on healthcare systems worldwide. Particularly, hepatitis B and C are viral infections that can lead to severe liver damage, cirrhosis, and even hepatocellular carcinoma (HCC). The urgency to combat these diseases has driven researchers to explore existing small-molecule drugs as potential therapeutics. This comprehensive review provides a systematic overview of synthetic routes to key antiviral agents used to manage hepatitis. Furthermore, it elucidates the mechanisms of action of these drugs, shedding light on their interference with viral replication and liver disease progression. The review also discusses the clinical applications of these drugs, including their use in combination therapies and various patient populations. By evaluating the synthetic pathways and clinical utility of these drugs, this review not only consolidates current knowledge but also highlights potential future directions for research and drug development in the fight against hepatitis, ultimately contributing to improved patient outcomes and reduced global disease burden.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Vírus da Hepatite B
16.
Eur J Med Chem ; 261: 115868, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37844346

RESUMO

Lung cancer continues to pose a significant challenge as a prominent contributor to global cancer-related mortality. Despite the considerable strides made in therapeutic interventions within the past decade, a substantial population of patients diagnosed with non-small cell lung cancer (NSCLC) still face the grim reality of an incurable condition. In the realm of optimal management strategies for individuals afflicted with locally advanced, yet amenable to surgical resection, NSCLC, a therapeutic approach encompassing chemoradiation stands as a fundamental component. Significant strides have been made in the therapeutic landscape of NSCLC during the preceding two decades, facilitating an enhanced comprehension of the underlying disease biology, and mechanisms governing tumor progression, as well as advancements in early detection modalities and multimodal therapeutic interventions. Nevertheless, the overall rates of curative interventions and survival outcomes for NSCLC continue to exhibit a discouragingly low trajectory, particularly in the context of metastatic disease. Hence, the imperative for sustained research endeavors in the realm of novel pharmaceutical agents and combinatorial therapeutic approaches remains paramount, with the overarching objective of broadening the scope of clinical advantages conferred upon a wider demographic of patients, thereby fostering tangible improvements in outcomes pertaining to NSCLC. The primary objective of this review is to provide an all-encompassing examination encompassing the clinical application and synthetic routes of specific drugs, with the explicit aim of disseminating invaluable knowledge that can inform future research and development endeavors focused on NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia Combinada
17.
Anal Chem ; 95(38): 14297-14307, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37718478

RESUMO

In this paper, a photoelectrochemical (PEC)-surface-enhanced Raman scattering (SERS) dual-mode biosensor is constructed coupled with a dual-recognition binding-induced DNA walker with a carbon nitride nanosheet (C3N4)/MXene-gold nanoparticles (C/M-Au NPs) accelerator, which is reliable and capable for sensitive and accurate detection of Staphylococcus aureus (S. aureus). Initially, a photoactive heterostructure is formed by combining C3N4 and MXene via a simple electrostatic self-assembly as they possess well-matched band-edge energy levels. Subsequently, in situ growth of gold nanoparticles on the formed surface results in better PEC performance and SERS activity, because of the synergistic effects of surface plasmon resonance and Schottky barrier. Furthermore, a three-dimensional, bipedal, and dual-recognition binding-induced DNA walker is introduced with the formation of Pb2+-dependent DNAzyme. In the presence of S. aureus, a significant quantity of intermediate DNA (I-DNA) is generated, which can open the hairpin structure of Methylene Blue-tagged hairpin DNA (H-MB) on the electrode surface, thereby enabling the switch of signals for the quantitative determination of S. aureus. The constructed PEC-SERS dual-mode biosensor that can be mutually verified under one reaction effectively addresses the problem of the low detection accuracy of traditional sensors. Experimental results revealed that the effective combination of PEC and SERS is achieved for amplification detection of S. aureus with a detection range of 5-108 CFU/mL (PEC) and 10-108 CFU/mL (SERS), and a detection of limit of 0.70 CFU/mL (PEC) and 1.35 CFU/mL (SERS), respectively. Therefore, this study offers a novel and effective dual-mode sensing strategy, which has important implications for bioanalysis and health monitoring.


Assuntos
Nanopartículas Metálicas , Infecções Estafilocócicas , Humanos , Ouro , Staphylococcus aureus , DNA
18.
Eur J Med Chem ; 261: 115827, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37757658

RESUMO

Myeloid leukemia denotes a hematologic malignancy characterized by aberrant proliferation and impaired differentiation of blood progenitor cells within the bone marrow. Despite the availability of several treatment options, the clinical outlook for individuals afflicted with myeloid leukemia continues to be unfavorable, making it a challenging disease to manage. Over the past, substantial endeavors have been dedicated to the identification of novel targets and the advancement of enhanced therapeutic modalities to ameliorate the management of this disease, resulting in the discovery of many clinically approved small-molecule drugs for myeloid leukemia, including histone deacetylase inhibitors, hypomethylating agents, and tyrosine kinase inhibitors. This comprehensive review succinctly presents an up-to-date assessment of the application and synthetic routes of clinically sanctioned small-molecule drugs employed in the treatment of myeloid leukemia. Additionally, it provides a concise exploration of the pertinent challenges and prospects encompassing drug resistance and toxicity. Overall, this review effectively underscores the considerable promise exhibited by clinically endorsed small-molecule drugs in the therapeutic realm of myeloid leukemia, while concurrently shedding light on the prospective avenues that may shape the future landscape of drug development within this domain.


Assuntos
Leucemia Mieloide Aguda , Leucemia Mieloide , Humanos , Estudos Prospectivos , Medula Óssea , Leucemia Mieloide Aguda/tratamento farmacológico
19.
Int J Nanomedicine ; 18: 2275-2293, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37159806

RESUMO

Introduction: In order to diagnose and treat papillary thyroid carcinoma (PTC) accurately, phase-transition nanoparticles, P@IP-miRNA (PFP@IR780/PLGA-bPEI-miRNA338-3p), was engineered. The nanoparticles (NPs) can target the tumor cells, realize the multimodal imaging, and provide sonodynamic-gene therapy for PTC. Methods: P@IP-miRNA NPs were synthesized through double emulsification method, and miRNA338-3p was attached to the surface of the NPs by electrostatic adsorption. The characterization of NPs was detected to screen out qualified nanoparticles. In vitro, laser confocal microscopy and flow cytometry were used to detect the targeting and subcellular localization of NPs. Western blot, qRT-PCR, and immunofluorescence were used to detect the ability to transfect miRNA. CCK8 kit, laser confocal microscopy and flow cytometry were used to detect the inhibition on TPC-1 cells. In vivo experiments were performed based on tumor-bearing nude mice. The efficacy of combined treatment by NPs was comprehensively evaluated, and the multimodal imaging ability of NPs in vivo and in vitro was detected. Results: P@IP-miRNA NPs were successfully synthesized which have spherical shape, uniform size, good dispersion and positive potential. The encapsulation rate of IR780 was (82.58±3.92) %, the drug loading rate was (6.60±0.32) %, and the adsorption capacity of miRNA338-3p was 41.78 µg/mg. NPs have excellent tumor targeting ability, miRNA transfection ability, ROS production ability and multimodal imaging ability in vivo and in vitro. The antitumor effect of combined treatment group was the best, and the efficacy was better than that of single factor treatment group, and the difference was statistically significant. Conclusion: P@IP-miRNA NPs can realize multimodal imaging and sonodynamic-gene therapy, providing a new idea for accurate diagnosis and treatment of PTC.


Assuntos
Carcinoma Papilar , Nanopartículas , Neoplasias da Glândula Tireoide , Animais , Camundongos , Câncer Papilífero da Tireoide , Camundongos Nus , Terapia Genética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/terapia
20.
Eur J Med Chem ; 250: 115172, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36758304

RESUMO

The development of heterocyclic derivatives has progressed considerably over the past few decades, and many new agents of synthetic and natural origin have been produced. Among heterocyclic compounds, thiazole is a unique five-membered heterocyclic motif characterized by nitrogen and sulfur atoms, which is widely used as an important core skeleton in a variety of pharmaceutically important compounds due to their diverse biological activities, such as antibacterial, antivirus, and antifungal. To the best of our knowledge, more than 90 thiazole-containing derivatives have been currently under clinical investigation, and some thiazole analogs have been approved to treat various diseases. As the potentially privileged scaffolds, thiazole derivatives can be further extensively explored to search for new drugs characterized by improved therapeutic efficacy and similar biological targets. This review aims to outline the applications and synthetic routes of some representative thiazole-containing drugs approved in the clinic, which may guide medicinal researchers to rationally design more effective thiazole-containing drug candidates.


Assuntos
Compostos Heterocíclicos , Tiazóis , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico
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