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The column chromatography with silica gel, reversed-phase C_(18), and Sephadex LH-20 was employed to separate the methanol extract of the aerial parts of Hypericum elatoides. The compounds were identified by the comprehensive analysis of IR, NMR, and MS data as methyl 8-O-ß-D-glucopyranosyl-(Z)-5-octenoate(1), methyl 3-O-ß-D-glucopyranosyl-4-methylhexanoate(2), byzantionoside B(3), 9-epi-blumenol C glucoside(4), corchoionoside C(5),(6S,9R)-roseoside(6), cis-p-coumaric acid 4-O-ß-D-glucopyranoside(7), trans-p-coumaric acid 4-O-ß-D-glucopyranoside(8), methyl 3-(4-hydroxyphenyl)propanoate(9),(E)-chlorogenic acid methyl ester(10), quercetin-3-O-ß-D-glucopyranoside(11), ß-sitosterol(12), stigmasterol(13), stigmast-4-en-3-one(14), ß-amyrin(15), daucosterol(16), sitoindoside â (17), oleic acid(18), methyl α-linolenate(19), trilinolein(20), and cassipourol(21). Among them, compounds 1 and 2 were identified as new glycosides and named hyperelatosides G and H. Compounds 3-5, 7-9, 17, and 20-21 were isolated from the genus Hypericum for the first time. The remaining compounds were isolated from H. elatoides for the first time. The results of biological assays revealed that compound 11 exhibited significant anti-neuroinflammatory activity, and compounds 1, 3, and 19 displayed certain neuroprotective effects.
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Glicósidos , Hypericum , Hypericum/química , Glicósidos/química , Glicósidos/aislamiento & purificación , Estructura Molecular , Medicamentos Herbarios Chinos/química , Espectroscopía de Resonancia MagnéticaRESUMEN
Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.
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Hypericum , Hypericum/química , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética , Lactonas/farmacología , Lactonas/química , Transducción de Señal , Estructura Molecular , Óxido NítricoRESUMEN
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved response in all stages of patients with EGFR positive mutations in nonsmall cell lung cancer. However, the primary resistance mechanism of EGFR-TKIs has not been thoroughly revealed. Here, we described a case of a 64-year-old male with lung adenocarcinoma presented primary resistance on osimertinib combined with bevacizumab and platinum-based chemotherapy, next-generation sequencing revealed EGFR exon 21 L858R mutation and MET gene amplification. Afterward, savolitinib monotherapy was started until now, and the treatment was temporarily successful, the last follow-up clinical evaluation was near complete response, the progression-free survival has over 7 months. Our case highlights that EGFR-TKIs may be not the optimal choice for lung adenocarcinoma with primary EGFR -sensitive mutation with MET amplification simultaneously, whereas MET inhibitor alone may be an effective treatment option. In clinical practice, we should fully consider the possibility of primary resistance in EGFR-TKIs administration.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acrilamidas , Adenocarcinoma del Pulmón/tratamiento farmacológico , Compuestos de Anilina/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Humanos , Indoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Pirazinas , Pirimidinas , TriazinasRESUMEN
BACKGROUND: The aim of this study is to assess the incidence, clinical manifestations, management, and prognosis of graft infection after bypass surgery with prosthetic conduit for infectious femoral artery pseudoaneurysms (IFAPs) in patients with a history of intravenous drug use (IVDU). METHODS: A single-center retrospective chart review of IVDU presenting with graft infections after previously being treated with extra-anatomic prosthetic conduit bypass surgery for IFAPs between 2009 and 2019 was performed. Relevant clinical data and patient demographics were collected and analyzed. All patients underwent procedures consisting of graft removal with analysis of operative details and complications. RESULTS: Of all 122 patients who underwent IFAP resection with extra-anatomic prosthetic bypass, the incidence of graft infection was 38.5% (47 patients, 48 grafts) with an average age of 35.7 ± 7.3 years. The average interval between bypass surgery and infectious symptoms was 9.2 ± 2.5 months and average time from bypass to graft removal was 13.6 ± 3.4 months. The most common presentation was repeated or unhealable chronic ulcers with sinus formation or purulence either within the bypass area or along the graft conduit route (43, 89.6%). Occlusion of the infected bypass graft occurred in nearly all cases (46, 95.8%). Severe hemorrhage occurred in only 1 case (2.1%). After graft removal, the stumps were ligated in the majority of patients (33, 68.8%) with 15 patients (31.2%) not amenable to ligation due to a difficult dissection. The average time of operation was 35.4 ± 8.7 min with an average blood loss of 35.8 ± 6.7 mL. There were no significant complications such as infection reoccurrence, severe limb ischemia, amputation, or death observed postoperatively. CONCLUSIONS: Patients who receive bypass surgery with prosthetic conduit for IFAPs carry a high incidence of graft infection and subsequent occlusion. However, the presenting symptoms are generally mild, and the incidence of fatal complications is rare. This study suggests that a safe treatment option consists of direct graft removal without reconstruction. Additionally, the procedure proved to be relatively convenient and straightforward, which provides further support toward the strategy of treating IFAPs in IVDUs with pseudoaneurysm resection and prosthetic conduit bypass surgery.
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Aneurisma Falso/cirugía , Aneurisma Infectado/cirugía , Implantación de Prótesis Vascular/efectos adversos , Prótesis Vascular/efectos adversos , Remoción de Dispositivos , Arteria Femoral/cirugía , Infecciones Relacionadas con Prótesis/cirugía , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/microbiología , Aneurisma Infectado/diagnóstico por imagen , Aneurisma Infectado/microbiología , Implantación de Prótesis Vascular/instrumentación , Remoción de Dispositivos/efectos adversos , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/microbiología , Humanos , Ligadura , Masculino , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Infecciones Relacionadas con Prótesis/microbiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Aortic dissection (AD) refers to false lumen dissected from true lumen via the internal membrane when endovascular blood flows into the aortic wall through the cleavage, which is formed after endomembrane gape of the aortic wall. Aortic dissection is a disease of extreme danger. Pregnancy is an independent risk factor for aortic dissection. Pregnancy concurrent with aortic dissection rarely is seen, not to mention pregnancy concurrent with asymptomatic aortic dissection. CASE REPORT: We present the case of a 34-year-old female patient, who was 25+ weeks pregnant, concurrent with aortic dissection. She was accepted by our hospital and successfully treated. Retrospective analysis of clinical data was carried out in this paper by combining related literature. CONCLUSION: This disease should be correctly straightened out to prevent misdiagnosis and save the patient's life. Multidisciplinary joint decisions should be made to save lives of the patient and her fetus.
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Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Disección Aórtica/diagnóstico , Angiografía por Tomografía Computarizada/métodos , Procedimientos Endovasculares/métodos , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Ultrasonografía/métodos , Adulto , Disección Aórtica/cirugía , Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Enfermedades Asintomáticas , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/cirugíaRESUMEN
Natural helicid (4-formylphenyl-O-ß-d-allopyranoside), a main active constituent from seeds of the Chinese herb Helicia nilagirica, has been reported to exert a sedative, analgesic and hypnotic effect, and is used clinically to treat neurasthenic syndrome, vascular headaches and trigeminal neuralgia. In the current study, mechanical allodynia tests, electroencephalograms, electromyogram recordings and c-Fos expression in neuropathic pain-like model mice of partial sciatic nerve ligation were used to investigate the effect of helicid on neuropathic pain and co-morbid insomnia. Our results showed that helicid at a dose of 100, 200 or 400 mg kg-1 could increase the mechanical threshold by 2.5-, 2.8- and 3.1-fold for 3 h after administration, respectively. Helicid at 200 and 400 mg kg-1 given at 07:00 hours increased the amount of non-rapid eye movement sleep in a 3-h period by 1.27- and 1.35-fold in partial sciatic nerve ligated mice. However, helicid (400 mg kg-1 ) given at 21:00 hours did not change the sleep pattern in normal mice. Immunohistochemical study showed that helicid (400 mg kg-1 ) administration could reverse the increase of c-Fos expression in the neurons of the rostral anterior cingulate cortex and tuberomammillary nucleus, and the decrease of c-Fos expression in the ventrolateral preoptic area caused by partial sciatic nerve ligation. These results indicate that helicid is an effective agent for both neuropathic pain and sleep disturbances in partial sciatic nerve ligated mice.
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Benzaldehídos/uso terapéutico , Neuralgia/complicaciones , Neuralgia/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/prevención & control , Analgésicos/administración & dosificación , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Benzaldehídos/administración & dosificación , Benzaldehídos/farmacología , Modelos Animales de Enfermedad , Electroencefalografía , Electromiografía , Genes fos/genética , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/metabolismo , Hiperalgesia/diagnóstico , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/uso terapéutico , Área Hipotalámica Lateral/efectos de los fármacos , Área Hipotalámica Lateral/metabolismo , Ligadura , Masculino , Ratones , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Nervio Ciático , Sueño/efectos de los fármacos , Sueño/fisiologíaRESUMEN
A modified generalized sidelobe canceller (IGSC) algorithm is proposed to enhance the resolution and robustness against the noise of the traditional generalized sidelobe canceller (GSC) and coherence factor combined method (GSC-CF). In the GSC algorithm, weighting vector is divided into adaptive and non-adaptive parts, while the non-adaptive part does not block all the desired signal. A modified steer vector of the IGSC algorithm is generated by the projection of the non-adaptive vector on the signal space constructed by the covariance matrix of received data. The blocking matrix is generated based on the orthogonal complementary space of the modified steer vector and the weighting vector is updated subsequently. The performance of IGSC was investigated by simulations and experiments. Through simulations, IGSC outperformed GSC-CF in terms of spatial resolution by 0.1 mm regardless there is noise or not, as well as the contrast ratio respect. The proposed IGSC can be further improved by combining with CF. The experimental results also validated the effectiveness of the proposed algorithm with dataset provided by the University of Michigan.
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Algoritmos , Quistes/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Ondas Ultrasónicas , Ultrasonografía/métodos , Simulación por Computador , Modelos Teóricos , Movimiento (Física) , Fantasmas de Imagen , Ultrasonografía/instrumentaciónRESUMEN
It is possible to recover a signal below the Nyquist sampling limit using a compressive sensing technique in ultrasound imaging. However, the reconstruction enabled by common sparse transform approaches does not achieve satisfactory results. Considering the ultrasound echo signal's features of attenuation, repetition, and superposition, a sparse dictionary with the emission pulse signal is proposed. Sparse coefficients in the proposed dictionary have high sparsity. Images reconstructed with this dictionary were compared with those obtained with the three other common transforms, namely, discrete Fourier transform, discrete cosine transform, and discrete wavelet transform. The performance of the proposed dictionary was analyzed via a simulation and experimental data. The mean absolute error (MAE) was used to quantify the quality of the reconstructions. Experimental results indicate that the MAE associated with the proposed dictionary was always the smallest, the reconstruction time required was the shortest, and the lateral resolution and contrast of the reconstructed images were also the closest to the original images. The proposed sparse dictionary performed better than the other three sparse transforms. With the same sampling rate, the proposed dictionary achieved excellent reconstruction quality.
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Recent advances in large language models are enabling the computational intelligent analysis of psychology in natural language. Here, the Fill-Mask Association Test (FMAT) is introduced as a novel and integrative method leveraging Masked Language Models to study and measure psychology from a propositional perspective at the societal level. The FMAT uses Bidirectional Encoder Representations from Transformers (BERT) models to compute semantic probabilities of option words filling in the masked blank of a designed query (i.e., a clozelike contextualized sentence). The current research presents 15 studies that establish the reliability and validity of the FMAT in predicting factual associations (Studies 1A-1C), measuring attitudes/biases (Studies 2A-2D), capturing social stereotypes (Studies 3A-3D), and retrospectively delineating lay perceptions of sociocultural changes over time (Studies 4A-4D). Empirically, the FMAT replicated seminal findings previously obtained with human participants (e.g., the Implicit Association Test) and other big-data text-analytic methods (e.g., word frequency analysis, the Word Embedding Association Test), demonstrating robustness across 12 BERT model variants and diverse training text corpora. Theoretically, the current findings substantiate the propositional (vs. associative) perspective on how semantic associations are represented in natural language. Methodologically, the FMAT allows for more fine-grained language-based psychological measurement, with an R package developed to streamline its workflow for use on broader research questions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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How are Asian and Black men and women stereotyped? Research from the gendered race and stereotype content perspectives has produced mixed empirical findings. Using BERT models pre-trained on English language books, news articles, Wikipedia, Reddit and Twitter, with a new method for measuring propositions in natural language (the Fill-Mask Association Test, FMAT), we explored the gender (masculinity-femininity), physical strength, warmth and competence contents of stereotypes about Asian and Black men and women. We find that Asian men (but not women) are stereotyped as less masculine and less moral/trustworthy than Black men. Compared to Black men and Black women, respectively, both Asian men and Asian women are stereotyped as less muscular/athletic and less assertive/dominant, but more sociable/friendly and more capable/intelligent. These findings suggest that Asian and Black stereotypes in natural language have multifaceted contents and gender nuances, requiring a balanced view integrating the gender schema theory and the stereotype content model. Exploring their semantic representations as propositions in large language models, this research reveals how intersectional race-gender stereotypes are naturally expressed in real life.
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Aim: A rapid and precise diagnostic method is crucial for timely intervention and management of tuberculosis. The present study compared the diagnostic accuracy of a novel lipoarabinomannan (LAM) antigen test, AIMLAM, for tuberculosis in urine samples. Methodology: The study subjected 106 TB suspects to smear microscopy, MGIT, GeneXpert and AIMLAM. Results: Among 106, smear microscopy identified 36 as positive (33%) (sensitivity; 70.93%, 95% CI (60.14-80.22%), while MGIT showed 38 positive (36.8%). GeneXpert detected 59 positives (sensitivity; 96.83, 95% CI (89.00-99.61%)). AIMLAM declared 61 as positive (57.5%) (sensitivity; 100.00, 95% CI (94.13-100.00%) and 45 as negative (42.5%). Conclusion: Overall, AIMLAM demonstrated better diagnostic accuracy than GeneXpert Assay, smear microscopy and MGIT liquid culture in urine samples.
This study describes a new way to detect tuberculosis, called AIMLAM. Unlike traditional methods that use sputum or blood, AIMLAM tests urine samples and bodily fluids. It is automated and uses easily accessible samples to identify a tuberculosis infection, so may be a convenient and noninvasive option for healthcare providers. The test shows promising results in terms of accuracy and sensitivity.
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Lipopolisacáridos , Mycobacterium tuberculosis , Sensibilidad y Especificidad , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/orina , Lipopolisacáridos/orina , Lipopolisacáridos/análisis , Masculino , Femenino , Adulto , Antígenos Bacterianos/orina , Persona de Mediana Edad , Microscopía/métodos , Adulto Joven , AncianoRESUMEN
Sporadic hand, foot, and mouth disease (HFMD) outbreaks and other infectious diseases in recent years have frequently been associated with certain human enterovirus (HEV) serotypes. This study explored the prevalences and genetic characteristics of non-HEV71 and non-coxsackievirus A16 (CV-A16) human enterovirus-associated HFMD infections in Shenzhen, China. A total of 2,411 clinical stool specimens were collected from hospital-based surveillance for HFMD from 2008 to 2012. The detection of HEV was performed by real-time reverse transcription-PCR (RT-PCR) and RT-seminested PCR, and spatiotemporal phylogenetic analysis was performed based on the VP1 genes. A total of 1,803 (74.8%) strains comprising 28 different serotypes were detected. In the past 5 years, the predominant serotypes were HEV71 (60.0%), followed by CV-A16 (21.2%) and two uncommon serotypes, CV-A6 (13.0%) and CV-A10 (3.3%). However, CV-A6 replaced CV-A16 as the second most common serotype between 2010 and 2012. As an emerging pathogen, CV-A6 became as common a causative agent of HFMD as HEV71 in Shenzhen in 2012. Phylogenetic analysis revealed that little variation occurred in the Chinese HEV71 and CV-A16 strains. The genetic characteristics of the Chinese CV-A6 and CV-A10 strains displayed geographic differences. The CV-A6 and CV-A10 strains circulating in Shenzhen likely originated in Europe. It was found that human enteroviruses have a high mutation rate due to evolutionary pressure and frequent recombination (3.2 × 10(-3) to 6.4 ×10(-3) substitutions per site per year for HEV71, CV-A6, CV-A16, and CV-A10). Since certain serotypes are potential threats to the public health, this study provides further insights into the significance of the epidemiological surveillance of HFMD.
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Enterovirus/clasificación , Enterovirus/genética , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Filogeografía , ARN Viral/genética , Preescolar , China/epidemiología , Enterovirus/aislamiento & purificación , Evolución Molecular , Heces/virología , Femenino , Genotipo , Humanos , Lactante , Masculino , Epidemiología Molecular , Datos de Secuencia Molecular , Tasa de Mutación , Reacción en Cadena de la Polimerasa , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
The main aim of this study was to curate a COI barcode library of Chironomidae from the Tibetan Plateau (TP) as an essential supplement to the public database. Another aim is to evaluate the current status of the public database of Chironomidae in aspects of taxonomic coverage, geographic representation, barcode quality, and efficiency for molecular identification, the Tibetan Plateau, China. In this study, 512 individuals of Chironomidae from the TP were identified based on morphological taxonomy and barcode analysis. The metadata of public records of Chironomidae were downloaded from the BOLD, and the quality of the public barcodes was ranked using the BAGS program. The reliability of the public library for molecular identification was evaluated with the newly curated library using the BLAST method. The newly curated library comprised 159 barcode species of 54 genera, of which 58.4% of species were likely new to science. There were great gaps in the taxonomic coverage and geographic representation in the public database, and only 29.18% of barcodes were identified at the species level. The quality of the public database was of concern, with only 20% of species being determined as concordant between BINs and morphological species. The accuracy of molecular identification using the public database was poor, and about 50% of matched barcodes could be correctly identified at the species level at the identity threshold of 97%. Based on these data, some recommendations are included here for improving barcoding studies on Chironomidae. The species richness of Chironomidae from the TP is much higher than ever recorded. Barcodes from more taxonomic groups and geographic regions are urgently needed to fill the great gap in the current public database of Chironomidae. Users should take caution when public databases are adopted as reference libraries for the taxonomic assignment.
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Lakes on the Qinghai-Tibet Plateau (QTP) have been subject to multiple environmental pressures from rapid climate change and intensified human activity in recent decades. However, their ecological effects on the lake ecosystem remain largely unclear due to the lack of long-term monitoring data. This study presented the environmental and ecological changes of the lake Yamzhog Yumco (Southern QTP) over the past three decades based on multi-proxy analysis (geochemistry and sedaDNA) on a high-time resolution sediment core. The result showed that the lake exhibited a continuous eutrophication process from 2004 CE, which has accelerated since 2014 CE. The nutrient enrichment was mainly attributed to anthropogenic emissions from the catchment. The sedimentary ancient DNA (sedaDNA) metabarcoding data registered a sensitive response of aquatic communities to the additional nutrient supply. Eukaryotic algae and aquatic invertebrate communities exhibited similar temporal dynamics, characterized by the increase in eutrophic taxa and the decrease in oligotrophic taxa. Change points analysis suggested that lake ecosystems underwent a slight ecological shift in 2003 CE and an abrupt shift in 2012 CE driven by nutrient enrichment. Quantitative analysis revealed that nutrients and human activity accounted for 27.9 % and 21.7 % of the temporal variation in aquatic communities, whereas climate change only explained 6.9 % of the total variation. From a paleolimnological view, our study supported that regional human activity could distinctly alter the nutrient level and aquatic community structure of lake ecosystems in the QTP. Considering that anthropogenic disturbance will continuously increase, it is crucial to strengthen the field monitoring of the lakes on the plateau and make effective management measures to avoid irreversible ecological consequences.
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Ecosistema , Lagos , Humanos , Tibet , Efectos Antropogénicos , Eutrofización , ChinaRESUMEN
Rational design of low-cost and high-efficiency electrocatalysts for hydrogen evolution reaction (HER) is critical for scalable and sustainable hydrogen production from economical water-alkali splitting. Herein, density functional theory (DFT) calculations reveal that coupling NiOx and CoP could effectively boost overall HER kinetics through lowing the H2O dissociation barrier, accelerating the OH* transfer process, and providing the rapid H* migration kinetics as well as the appropriate H* energetics. Based on these findings, we successfully prepared a three-dimensional (3D) self-supported electrode of ultrathin CoP nanosheets directly grown on the surface-oxidized Ni nanotube arrays via a simple and scalable electrochemical synthesis method. As expected, such a heterostructure electrode exhibits superior alkaline HER performance with low overpotentials of 51 and 164 mV to drive the current densities of 10 and 500 mA cm-2, respectively, outperforming most of the efficient alkaline HER electrocatalysts.
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Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (ß-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of â¼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the "ELVIS" effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the "proton sponge" effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 µg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.
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Artritis Reumatoide , Nanopartículas , Ratas , Animales , Polielectrolitos/farmacología , Nanopartículas/química , Polímeros/farmacología , Artritis Reumatoide/tratamiento farmacológico , Macrófagos , Inflamación , Concentración de Iones de HidrógenoRESUMEN
Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.
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Dianthus , Dianthus/química , Ecdisterona/farmacología , Simulación del Acoplamiento Molecular , Enfermedades Neuroinflamatorias , Ecdisteroides/farmacologíaRESUMEN
Objectives: Neoadjuvant immunochemotherapy (nICT) has been confirmed with promising pathological complete response (pCR) among locally advanced esophageal squamous cell carcinoma (ESCC). However, there were still no reliable and accurate predictors to predict the treatment response. This study aimed to explore the predictive value of inflammatory and nutritional parameters. Methods: Patients with ESCC who underwent radical surgery after nICT between January 2020 and April 2022 were included in the study. First, the least absolute shrinkage and selection operator regression (LASSO) logistic regression analysis was used to screen independent inflammatory and nutritional parameters. Secondly, univariate and multivariate logistic regression were used to screen and predict independent risk factors for pCR. Thirdly, a nomogram was constructed based on the independent predictive factors, and 30% of the included population was randomly selected as the validation cohort. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model. Results: A total of 97 ESCC patients were screened for analysis, with 20 patients with pCR (20.32%). Only the systemic immune-inflammation index (SII) was screened after LASSO-logistic regression when λ was 0.06. The cut-off value of SII was 921.80 with an area under curve (AUC) value of 0.62. We defined SII > 921.80 as high SII and SII ⦠921.80 as low SII. Further, the univariate and multivariate analysis further determined SII(OR = 3.94, 95%CI:1.26-12.42, P = 0.02) and clinical stage(OR = 0.35, 95%CI:0.12-0.98, P = 0.05) were independent predictive factors of pCR. One novel nomogram was established with an AUC value of 0.72 in the training cohort and 0.82 in the validation cohort. The Brier score of the calibration curve was 0.13. The calibration curve showed good agreement between the predicted results and the actual results in both the training cohort and the validation cohort. Compared with the clinical stage, the DCA confirmed a better clinical value of the nomogram model in both the training cohort and the validation cohort. Conclusions: High pretreatment SII and early clinical stage were independently associated with pCR among ESCC receiving nICT. We further established and validated one novel nomogram model to effectively predict pCR among ESCC after nICT.
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PURPOSE: The development of the premaxillary-maxillary suture (PMS) in human fetuses and a possible association between the fusion time of the PMS and maxillary deficiency were investigated. Expression of transforming growth factor beta (TGF-ß1 and TGF-ß3) and of fibulins (fibulin1 and fibulin-5) were also investigated. METHODS: We analyzed 36 human fetus cadavers (19 males, 17 females; average age 23.97⯱ 2.57 gestational weeks [gws], range 11-35 gws). Two cases, diagnosed with Down syndrome (DS), were characterized with maxillary deficiency; 34 fetus cadavers did not show any craniofacial abnormalities. The PMS was analyzed anatomically, followed by semi-quantitative immunohistochemical (IHC)-based expression analyses (i.e., TGF-ß1/-ß3, fibulin-1/-5). Spearman correlation test was conducted to investigate correlations. RESULTS: In the fetuses without DS, the labial region of the PMS was open at 11 gws, after which it began to ossify from the middle to the upper and lower ends of the suture, typically fusing completely at 27 gws. Fetuses with DS demonstrated complete fusion of the labial region of PMS with a spongy bone structure at 23 gws and those without DS at 27 gws. IHC revealed similar patterns of TGF-ßs and fibulins expression in the PMS during the human fetal period. There were significant positive correlations between the expression of TGF-ß1 and TGF-ß3 (râ¯= 0.64, pâ¯= 0.009), TGF-ß1 and fibulin1 (râ¯= 0.66, pâ¯= 0.008), and TGF-ß3 and fibulin1 (râ¯= 0.67, pâ¯= 0.006). CONCLUSION: Premature fusion of the PMS in the labial region during the human fetal period may be associated with maxillary deficiency, which is related to a class III malocclusion. Overall, the similar expression patterns of TGF-ß1, TGF-ß3 and fibulin1 suggested a close relationship between these factors in regulating the development of the PMS.