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1.
J Nanobiotechnology ; 21(1): 400, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907972

RESUMEN

Cancer has always posed a significant threat to human health, prompting extensive research into new treatment strategies due to the limitations of traditional therapies. Starvation therapy (ST) has garnered considerable attention by targeting the primary energy source, glucose, utilized by cancer cells for proliferation. Glucose oxidase (GOx), a catalyst facilitating glucose consumption, has emerged as a critical therapeutic agent for ST. However, mono ST alone struggles to completely suppress tumor growth, necessitating the development of synergistic therapy approaches. Metal catalysts possess enzyme-like functions and can serve as carriers, capable of combining with GOx to achieve diverse tumor treatments. However, ensuring enzyme activity preservation in normal tissue and activation specifically within tumors presents a crucial challenge. Nanodelivery systems offer the potential to enhance therapy effectiveness by improving the stability of therapeutic agents and enabling controlled release. This review primarily focuses on recent advances in the mechanism of GOx combined with metal catalysts for synergistic tumor therapy. Furthermore, it discusses various nanoparticles (NPs) constructs designed for synergistic therapy in different carrier categories. Finally, this review provides a summary of GOx-metal catalyst-based NPs (G-M) and offers insights into the challenges associated with G-M therapy, delivery design, and oxygen (O2) supply.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Neoplasias , Humanos , Glucosa Oxidasa , Sistema de Administración de Fármacos con Nanopartículas , Neoplasias/terapia , Metales , Glucosa , Línea Celular Tumoral , Peróxido de Hidrógeno
2.
BMC Biol ; 19(1): 115, 2021 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-34082735

RESUMEN

BACKGROUND: Many of genome features which could help unravel the often complex post-speciation evolution of closely related species are obscured because of their location in chromosomal regions difficult to accurately characterize using standard genome analysis methods, including centromeres and repeat regions. RESULTS: Here, we analyze the genome evolution and diversification of two recently diverged sister cotton species based on nanopore long-read sequence assemblies and Hi-C 3D genome data. Although D genomes are conserved in gene content, they have diversified in gene order, gene structure, gene family diversification, 3D chromatin structure, long-range regulation, and stress-related traits. Inversions predominate among D genome rearrangements. Our results support roles for 5mC and 6mA in gene activation, and 3D chromatin analysis showed that diversification in proximal-vs-distal regulatory-region interactions shape the regulation of defense-related-gene expression. Using a newly developed method, we accurately positioned cotton centromeres and found that these regions have undergone obviously more rapid evolution relative to chromosome arms. We also discovered a cotton-specific LTR class that clarifies evolutionary trajectories among diverse cotton species and identified genetic networks underlying the Verticillium tolerance of Gossypium thurberi (e.g., SA signaling) and salt-stress tolerance of Gossypium davidsonii (e.g., ethylene biosynthesis). Finally, overexpression of G. thurberi genes in upland cotton demonstrated how wild cottons can be exploited for crop improvement. CONCLUSIONS: Our study substantially deepens understanding about how centromeres have developed and evolutionarily impacted the divergence among closely related cotton species and reveals genes and 3D genome structures which can guide basic investigations and applied efforts to improve crops.


Asunto(s)
Centrómero , Gossypium , Centrómero/genética , Cromatina , Regulación de la Expresión Génica de las Plantas , Genoma de Planta/genética , Gossypium/genética , Filogenia
3.
Genomics ; 113(4): 2317-2326, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34048909

RESUMEN

Chichi is a unique biological phenomenon observed in Ginkgo biloba L.. In this study, multi-omics analysis was used to compare basal chichi (C) with roots (R) and stems (S) to explore the regulatory mechanisms of basal chichi ontogenesis. The results showed that compared with roots and stems, the tZ, SA and ABA contents in basal chichi were the highest, and the ratio of IAA/tZ was the lowest. Nucleotides and their derivatives in basal chichi were upregulated, and phenylpropane metabolites were downregulated. Some differentially expressed genes (DEGs) strongly correlated to plant hormones were screened. We speculate that auxin and cytokinin are involved in the morphogenesis of basal chichi and that cytokinin plays a major role. The ontogenesis of basal chichi is closely related to environmental stress, and it may be a coping strategy of G. biloba in the face of environmental stress.


Asunto(s)
Ginkgo biloba , Transcriptoma , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/genética
4.
Inflamm Res ; 70(2): 241-247, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33385239

RESUMEN

OBJECTIVES: To investigate the relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and immunity alteration for patients after 6-month hospital discharge. METHODS: One IgM(+) and IgG(-), 32 IgM(+) and IgG(+), 38 IgM(-) and IgG(+), and 40 IgM(-) and IgG(-) patients were included. Demographic data were collected. IgM and IgG antibodies, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and lymphocyte subsets in serum were determined at weeks 0, 2 and 4. RESULTS: The hs-CRP and IL-6 levels of all patients were within the normal ranges. The number of patients with all lymphocyte subset testing items within normal ranges was 12/110 (10.9%) at week 0, 15/110 (13.6%) at week 2 and 18/110 (16.4%) at week 4. The percentages of CD8 + cells, NK cells and B lymphocytes in the IgM(+) and IgG(+) group were quite different from those in the IgM(-) and IgG(+) group and the IgM(-) and IgG(-) group, with much higher percentages of CD8 + cells and much lower percentages of NK cells and B lymphocytes at weeks 0, 2 and 4. Twelve IgM(+) patients in the IgM(+) and IgG(+) group converted to IgM(-), and the percentages of NK cells and B lymphocytes in these patients were significantly increased at week 4. CONCLUSIONS: The changes of serum IgM and IgG are closely related to immunity in patients in the recovery stage. However, immunity does not recover when the patients test negative for these antibodies.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , SARS-CoV-2/inmunología , Adulto , Anciano , Linfocitos B/inmunología , Ejercicios Respiratorios , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Alta del Paciente , Adulto Joven
5.
BMC Infect Dis ; 21(1): 371, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33879073

RESUMEN

BACKGROUND: The current coronavirus disease 2019 (COVID-19) is a public health emergency. In this study, we aimed to evaluate the risk factors for mortality in severe and critical COVID-19 patients. METHODS: We performed a retrospective study of patients diagnosed with severe and critical COVID-19 from four hospitals in Wuhan, China, by evaluating the clinical characteristics and laboratory results, and using Cox proportional hazards model to assess the risk factors involved in disease progression. RESULTS: In total, 446 patients with COVID-19 were enrolled. The study indicated a high mortality rate (20.2%) in severe and critical COVID-19 patients. At the time of admission, all patients required oxygen therapy, and 52 (12%) required invasive mechanical ventilation, of which 50 (96%) died. The univariate Cox proportional hazards model showed a white blood cell count of more than 10 × 109/L (HR 3.993,95%CI 2.469 to 6.459) that correlated with an increased mortality rate. The multivariable Cox proportional hazards model demonstrated that older age (HR 1.066, 95% CI 1.043 to 1.089) and higher white blood cell count (HR 1.135, 95% CI 1.080 to 1.192) were independent risk factors for determining COVID-19 associated mortality. CONCLUSIONS: COVID-19 is associated with a significant risk of morbidity and mortality in the population. Older age and higher white blood cell count were found to be independent risk factors for mortality.


Asunto(s)
Factores de Edad , COVID-19/diagnóstico , Recuento de Leucocitos , Adulto , Anciano , COVID-19/fisiopatología , China/epidemiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Respiración Artificial , Estudios Retrospectivos , Factores de Riesgo
6.
Opt Express ; 28(21): 31093-31102, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33115091

RESUMEN

Photosensitivity in photo-thermo-refractive (PTR) glass can be triggered by UV and near-infrared fs laser irradiation. Here we focus on the nonlinear photochemical process triggered by ultrashort laser Gaussian-Bessel beams. The transmission and absorption spectra show that the primary difference between UV and fs laser exposure is the formation of color centers and kinetic process of silver nanoparticles growth. It is contributed to the nonlinear ionization of PTR glass matrix and thermal effects during interaction of glass matrix and ultrashort laser pulses. Transmission electron microscopy verifies the generation of nanoscale crystals in the irradiated region, and X-ray diffraction shows the existence of quartz crystal and NaF after laser irradiation and thermal treatment. Moreover, the dependence of photochemical reaction on laser parameters is investigated, as well as the tailoring of silver nanoparticles. On this basis, volume Bragg gratings with ultrashort laser Gaussian-Bessel beams are inscribed as an application which possess good diffraction characteristics.

7.
Mediators Inflamm ; 2019: 8387636, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30944548

RESUMEN

The aim of this study was to study the protective effect of Huang Qi Tong Bi Decoction (HQTBT) on the heart of rats. Ischemia-reperfusion injury was established by coronary artery ligation. Proinflammatory cytokines were decreased by XFZY in coronary artery ligated rats. ST segment was also restored with the treatment of HQTBT. Triphenyltetrazole chloride (TTC) staining and pathological analysis showed that HQTBT reduced myocardial injury. Besides, the expressions of HMGB1/TLR/NF-κB pathway in rats were significantly decreased by HQTBT. This study shows that HQTBT inhibited inflammatory reaction on myocardial injury in rats.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Proteína HMGB1/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , FN-kappa B/metabolismo , Receptores Toll-Like/metabolismo , Animales , Astragalus propinquus , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
8.
Biomed Chromatogr ; 33(2): e4376, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30168866

RESUMEN

Shuang Huang Lian Injection (SHLI) has been used in China for over 30 years as an effective and widely used Chinese herbal prescription to treat acute respiratory infectious. SHLI has, however, caused many severe anaphylactoid reactions. It is important to identify the potential anaphylactoid components of SHLI. Spectrum-effect relationships were used to explore potentially anaphylactoid components. Based on the original herbal formula, honeysuckle, Fructus Forsythiae and Radix Scutellariae extracts were prepared and combined in appropriate proportions. The preparations were then injected into the caudal vein of rats to obtain in vivo serum samples for pharmacological evaluation and fingerprint analysis. The release rate of ß-hexosaminidase from RBL-2H3 cells and plasma histamine level was used as the pharmacological index. Chromatographic fingerprint analysis identified 22 common peaks. Regression analysis and correlation analysis were used to calculate the relationships between the peaks and the pharmacological effects and identified peaks 5, 6, 11, 12 and 17 as likely anaphylactoid agents. The correlated peaks were identified by comparing the fingerprints with in vitro samples and reference standard samples and the structure was identified by UPLC-TOF-MS. This study established a prospective method to clarify the anaphylactoid components in SHLI, which would provide guidances for screening anaphylactoid components in other traditional Chinese medicine injections.


Asunto(s)
Antígenos de Plantas/análisis , Medicamentos Herbarios Chinos/análisis , Anafilaxia , Animales , Antígenos de Plantas/química , Línea Celular , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Femenino , Hexosaminidasa B/sangre , Hexosaminidasa B/metabolismo , Histamina/sangre , Lonicera/química , Masculino , Espectrometría de Masas , Ratas , Ratas Wistar
9.
Molecules ; 24(17)2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31480782

RESUMEN

In order to evaluate the application potential of rainbow trout (Oncorhynchus mykiss) heads and skipjack tuna (Katsuwonus pelamis) heads; proximate composition, amino acids, fatty acids, carnosine, and anserine contents were analyzed in this study. Rainbow trout heads showed significantly higher protein (29.31 g/100 g FW, FW is abbreviation of fresh weight) and lipid (6.03 g/100 g FW) contents than skipjack tuna heads (18.47 g/100 g FW protein and 4.83 g/100 g FW lipid) (p < 0.05). Rainbow trout heads and skipjack tuna heads exhibited similar amino acid composition. Essential amino acids constituted more than 40% of total amino acids in both rainbow trout head and skipjack tuna head. The fatty acid profile was different between rainbow trout heads and skipjack tuna heads. Rainbow trout heads mainly contained 38.64% polyunsaturated fatty acids (PUFAs) and 38.57% monounsaturated fatty acids (MUFAs), whereas skipjack tuna heads mainly contained 54.46% saturated fatty acids (SFAs). Skipjack tuna heads contained 4563 mg/kg FW anserine and 1761 mg/kg FW carnosine, which were both significantly higher than those of rainbow trout heads (p < 0.05). These results demonstrate that both rainbow trout heads and skipjack tuna heads may be used as materials for recycling high-quality protein. Meanwhile, rainbow trout heads can be used to extract oil with high contents of unsaturated fatty acids, while skipjack tuna heads may be a source for obtaining carnosine and anserine.


Asunto(s)
Estado Nutricional , Oncorhynchus mykiss/metabolismo , Aminoácidos/metabolismo , Animales , Anserina/química , Carnosina/química , Ácidos Grasos/metabolismo , Cabeza , Reproducibilidad de los Resultados , Atún
10.
Appl Opt ; 57(27): 7943-7949, 2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30462065

RESUMEN

By applying an optimized chelate gas phase deposition technique, a Yb/Ce codoped aluminosilicate fiber with ultra-low loss of 1.55 dB/km was successfully fabricated and reported. The fiber showed homogenous distribution of the refractive index and dopant concentration devoid of central dip and clustering. Using the fiber as the amplifier stage, it delivered 1023 W near-single-mode laser output (M2=1.35) with a high slope efficiency of 85.1%, and the fiber temperature was less than 24.2°C, primarily benefiting from the ultra-low background loss. The fiber also exhibited low photodarkening-induced loss, illustrating its outstanding photodarkening resistance. These results indicate that the ultra-low-loss Yb/Ce codoped aluminosilicate fiber is a prospective candidate for stable and reliable fiber laser applications.

11.
Appl Opt ; 55(10): 2649-52, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-27139668

RESUMEN

A high-power third-harmonic laser faces challenges in the filtering remnant unconverted fundamental frequency, which is from the frequency converting crystal. In this work, a novel fundamental-frequency-absorbed oxyfluoride glass has been prepared, which provides a possible option to solve the problem. By being doped with Fe2+ ion, the glass shows strong absorption property at 1053 nm, and the glass's transmittances at 351 and 1053 nm are stable with changing the laser power or increasing the irradiation times under high-power laser irradiation. Meanwhile, the laser-induced damage threshold of the glass is 12.5 J/cm2 at 351 nm, which is two times higher than that of fused silica whose threshold is 6.2 J/cm2 in the same testing condition. The glass also exhibits a higher laser-induced damage threshold as well as 36.6 J/cm2 at its absorption wavelength of 1053 nm. The results indicate that this glass is promising as a color-separation optic, thus allowing a novel design for the final optics assembly in an inertial confinement fusion laser system.

12.
Int J Food Sci Nutr ; 67(6): 650-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27251367

RESUMEN

During the aging process, dimers of dietary vitamin A accumulated in retinal pigment epithelium (RPE) cells. Vitamin A dimer-mediated photooxidation resulted in RPE apoptosis, which is associated with age-related degenerative disease of retina, leading to blindness. It has been reported that proanthocyanidin-rich grape seed extract reduces oxidative stress in the eye. In this study, we investigated the underlying mechanism of photooxidation-induced apoptosis inhibition by procyanidins B2 (PB2), one of the main components of grape seed proanthocyanidin. To mimic vitamin A dimer-mediated photooxidation, ARPE-19 cells that accumulated vitamin A dimer, A2E, were used as a model system. Exposure of A2E loaded ARPE-19 cells to blue light induced ER stress and resulted in significant apoptosis. Pretreatment of blue light-exposed A2E containing ARPE-19 cells with PB2 inhibited apoptosis, increased the ratio of Bcl-2/Bax in the mitochondria, attenuated ROS and cytochrome c release, and decreased caspase cleavage. Additionally, PB2 inhibited the phosphorylation of ER stress markers elF2α and IRE1α and reduced CHOP expression. Moreover, PB2 inhibition of apoptosis is dependent on the UPR chaperone GRP78, indicating PB2 inhibits vitamin A dimer-mediated apoptosis in RPE cells by activating the UPR.


Asunto(s)
Apoptosis/efectos de los fármacos , Biflavonoides/farmacología , Catequina/farmacología , Estrés Oxidativo/efectos de los fármacos , Proantocianidinas/farmacología , Vitamina A/efectos adversos , Línea Celular , Citocromos c/genética , Citocromos c/metabolismo , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Silenciador del Gen , Extracto de Semillas de Uva/farmacología , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Retina/citología , Retina/efectos de los fármacos , Retina/metabolismo , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
13.
Tumour Biol ; 36(9): 7061-7, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25869879

RESUMEN

Thyroid cancer 1 (TC1, C8orf4) plays important roles in many signaling pathways, such as Wnt/ß-catenin signaling pathway, and is involved in the development of many cancers. The objective of this study was to examine the expression of TC1 and investigate the associations among TC1, ß-catenin, Chibby, cyclin D1, and the clinicopathological factors of oral tongue squamous cell carcinomas (OTSCCs). The expressions of TC1, ß-catenin, Chibby, and cyclin D1 were examined in 109 cases of OTSCCs using immunohistochemistry. The expression of TC1 was observed in all cases of OTSCCs but was negative or weak in normal squamous epithelial tissues of tongue. The high expression of TC1 was correlated with the advanced TNM stage (P = 0.042), the abnormal expression of ß-catenin (correlation coefficient = 0.314, P = 0.001) and the expression of cyclin D1 (correlation coefficient = 0.274, P = 0.006) in OTSCCs. But we did not find any associations between TC1 and Chibby. The abnormal expression of ß-catenin was correlated with the poor differentiation (P = 0.035), advanced TNM stage (P = 0.048) and the expression of cyclin D1 (correlation coefficient = 0.422, P < 0.001). In conclusion, the high expression of TC1 was common in OTSCCs and correlated with the expression of ß-catenin and cyclin D1 and the progression of OTSCCs. The high expression level of TC1 might promote the progression of OTSCCs by enhancing the activity of Wnt signaling pathway.


Asunto(s)
Carcinoma de Células Escamosas/genética , Ciclina D1/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Lengua/genética , beta Catenina/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Ciclina D1/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Neoplasias de la Lengua/patología , Vía de Señalización Wnt , beta Catenina/genética
14.
Yao Xue Xue Bao ; 50(4): 434-9, 2015 Apr.
Artículo en Zh | MEDLINE | ID: mdl-26223124

RESUMEN

Poly(ß-amino esters) (PBAE) are used for drug carrier and have many advantages, such as pH-sensitivity, low toxicity, structural diversity and the synthetic method of PBAE is easy. Therefore they are possessed broad application prospect in tumor-targeted drugs delivery systems. In this paper, the structural features and target drugs delivery property of PBAE are reviewed. The application forms of PBAE and different anti-cancer drugs loaded in the copolymer for tumor-targeted drugs delivery systems are introduced particularly.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Ésteres/química , Neoplasias/tratamiento farmacológico , Concentración de Iones de Hidrógeno , Polímeros
15.
Discov Oncol ; 15(1): 21, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38285118

RESUMEN

Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (ß-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer.

16.
Fitoterapia ; : 106080, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901805

RESUMEN

Bioactive compounds derived from natural sources have long been investigated for the prevention and treatment of human diseases. Sophoraflavanone G (SFG), a lavandulyl flavanone naturally occurring in several Sophora plant species, belongs to the group of prenylated flavonoids that have garnered significant interest in contemporary research. The natural molecule exhibits a wide range of pharmacological properties and shows remarkable efficacy. Its ability to effectively suppress a range of malignant tumor cells, such as leukemia, breast cancer, and lung cancer, is attributed to its multi-target, multi-pathway, and multi-faceted mechanisms of action. Simultaneously, it can also alleviate various inflammatory diseases by mediating inflammatory mediators and molecular pathways. Furthermore, it has the capability to combat antibiotic resistance, exhibit synergistic antibacterial properties with diverse antibiotics, and prevent and treat various agricultural pests. Theoretically, it can bring benefits to human health and has potential value as a drug. Nevertheless, the drawbacks of poor water solubility and inadequate targeting cannot be overlooked. To comprehensively assess the current research on SFG, leverage its structural advantages and pharmacological activity, overcome its low bioavailability limitations, expedite its progression into a novel therapeutic drug, and better serve the clinic, this article presents a overall retrospect of the current research status of SFG. The discussion includes an analysis of the structural characteristics, physicochemical properties, bioavailability, pharmacological activities, and structure-activity relationships of SFG, with the goal of offering valuable insights and guidance for future research endeavors in this field.

17.
Org Lett ; 26(11): 2228-2232, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38457330

RESUMEN

A silver-catalyzed decarboxylative remote fluorination via a zwitterion-promoted 1,4-heteroaryl migration has been developed. A variety of heteroaryl-tethered benzyl fluorides have been readily synthesized with good regioselectivity under mild conditions. The zwitterion of the substrate is suggested to accelerate the 1,4-heteroaryl migration, which determines the regioselectivity of this transformation.

18.
Mol Cancer Ther ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940283

RESUMEN

Delta-like ligand 3 (DLL3) is overexpressed in small-cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine (Rova-T) was the first DLL3-targeted antibody-drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with Rova-T. In this study, we developed a novel DLL-3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody FZ-A038 and a valine-alanine (Val-Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line-derived xenografts (CDX) and patient-derived xenograft (PDX) models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of SCLC patients.

19.
Heliyon ; 10(10): e31365, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38818193

RESUMEN

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster.

20.
Aging (Albany NY) ; 16(5): 4503-4517, 2024 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-38412322

RESUMEN

BACKGROUND: Clinical studies have confirmed that Qingfei Dayuan (QFDY) granules are effective in the treatment of influenza and upper respiratory tract infections (URTIs) caused by pulmonary heat-toxin syndrome (PHTS). Granules of Chinese medicine formulations have become a widely used dosage form in clinical practice. With the continuous optimization of extraction technology, the advantages of Chinese medicine granules have been gradually demonstrated, but the price of Chinese medicine granules is generally higher than that of traditional dosage forms of Chinese medicine, and we support the rational use of the appropriate dosage of QFDY for patients with these conditions. Therefore, we set up half of the conventional dose as the low dose group, and designed the three-arm study to rigorously compare the efficacy difference of low-dose QFDY, QFDY and the placebo group, with the expectation of providing scientific support for the rational selection of the dose and the safe and effective use of the medicine in clinical practice. METHODS: We recruited 108 patients with clinical diagnoses of influenza and URTIs caused by PHTS to receive treatment at six hospitals in Hubei, China. Using a centralized randomization system, patients were randomly assigned at a 1:1:1 ratio to the QFDY, low-dose QFDY, or placebo control groups to receive the corresponding drug, and the study physicians, subjects, outcome assessors, and statisticians were unaware of group assignments. The primary outcome was the time to complete fever relief. Secondary outcomes included the efficacy of Chinese medicine in alleviating signs and symptoms and the disappearance rate of individual symptoms. Adverse events were monitored throughout the trial. RESULTS: A total of 108 patients were recruited. A total of 106 patients were included in the full analysis set (FAS). In the FAS analysis, there was no statistically significant difference in baseline of the three groups before treatment (P > 0.05). 1. Regarding the median time to complete fever relief, the QFDY, low-dose QFDY and placebo groups had median times of 26 h, 40 h and 48 h, respectively. The QFDY group had a shorter time to complete fever relief than the placebo group, and the difference was statistically significant (P < 0.05), while the low-dose QFDY group had a shorter time than the placebo group, but the difference was not statistically significant (P > 0.05). 2. In terms of the total efficacy of Chinese medicine in alleviating symptoms at the end of three full days of treatment, as well as the cure rate of red and sore throat, stuffy and runny nose, and sneezing, QFDY and low-dose QFDY were superior to the placebo, and the differences were statistically significant (P < 0.01). There was no statistical significance in the comparison between the QFDY group and the low-dose QFDY group (P > 0.05). 3. In terms of the headache cure rate after three full days of treatment, QFDY was superior to the placebo, with a statistically significant difference (P < 0.05), and there was no significant efficacy of low-dose QFDY. 4. Safety comparisons showed no serious adverse events and 30 minor adverse events, which were not clinically considered to be related to the drug and were not statistically significant. CONCLUSIONS: In the treatment of patients with influenza and URTIs caused by PHTS, which are mainly characterized by clinical symptoms such as red and sore throat, stuffy and runny nose, and sneezing, when fever is not obvious or low-grade fever is present, the use of low-dose QFDY to simply alleviate the clinical symptoms is recommended and preferred. Moreover, with its good safety profile, QFDY can be used in the treatment of patients with influenza and URTIs caused by PHTS, which can effectively shorten the duration of fever, significantly increase the total efficacy of Chinese medicine in alleviating symptoms after 3 days of treatment, and accelerate the recovery of symptoms such as red and sore throat, stuffy and runny nose, sneezing, and headache, etc. Clinical Trial Registration: http://www.chictr.org.cn. TRIAL NUMBER: ChiCTR2100043449. Registered on 18 February 2021.


Asunto(s)
Medicamentos Herbarios Chinos , Gripe Humana , Faringitis , Infecciones del Sistema Respiratorio , Humanos , Gripe Humana/tratamiento farmacológico , Estornudo , Fiebre/tratamiento farmacológico , Cefalea , Rinorrea , Resultado del Tratamiento
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