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1.
Crit Rev Immunol ; 44(6): 37-47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848292

RESUMO

BACKGROUND: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of the breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell's behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear. METHODS: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of the mammary gland of mice at different developmental stages, we examined the breast development of ER S309A mice. Using hematoxylin-eosin (HE) staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes. RESULTS: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, and estrous cycle disorder in ER S309A mice. The number of vaginal epithelial keratino-cytes in the estrous cycle of ER S309A mice was decreased. CONCLUSION: These results suggest that the phosphorylation site of ER at Serine 309 is important for ER function and breast development.


Assuntos
Serina , Animais , Feminino , Camundongos , Fosforilação , Serina/metabolismo , Humanos , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Mama/crescimento & desenvolvimento , Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Mutação
2.
Nature ; 574(7776): 86-89, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578481

RESUMO

Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties1. Copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) triazole annulation and sulfur(VI) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions2-4, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups5. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide6-11 (FSO2N3), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science.

3.
Bioorg Chem ; 145: 107210, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38364551

RESUMO

Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC50 value of 0.48 µM, significantly more effective than its parent compound HCG (IC50 > 100 µM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c, with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents.


Assuntos
Antineoplásicos , Compostos Organofosforados , Sapogeninas , Animais , Humanos , Estrutura Molecular , Sapogeninas/farmacologia , Peixe-Zebra , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Desenho de Fármacos
4.
Sensors (Basel) ; 24(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38257462

RESUMO

Thermal feedback plays an important role in tactile perception, greatly influencing fields such as autonomous robot systems and virtual reality. The further development of intelligent systems demands enhanced thermosensation, such as the measurement of thermal properties of objects to aid in more accurate system perception. However, this continues to present certain challenges in contact-based scenarios. For this reason, this study innovates by using the concept of semi-infinite equivalence to design a thermosensation system. A discrete transient heat transfer model was established. Subsequently, a data-driven method was introduced, integrating the developed model with a back propagation (BP) neural network containing dual hidden layers, to facilitate accurate calculation for contact materials. The network was trained using the thermophysical data of 67 types of materials generated by the heat transfer model. An experimental setup, employing flexible thin-film devices, was constructed to measure three solid materials under various heating conditions. Results indicated that measurement errors stayed within 10% for thermal conductivity and 20% for thermal diffusion. This approach not only enables quick, quantitative calculation and identification of contact materials but also simplifies the measurement process by eliminating the need for initial temperature adjustments, and minimizing errors due to model complexity.

5.
Phys Chem Chem Phys ; 25(6): 5237-5243, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36723263

RESUMO

Compressed hydrogen-rich compounds have received extensive attention as appealing contenders for superconductors. Here, we found several stable hydrides YZrH6, YZrH8, YZr3H16 and YZrH18, and a series of metastable clathrate hexahydrides in the systematic investigation of Y-Zr-H ternary hydrides under pressure. Electron-phonon coupling calculations indicate that they all exhibit high temperature superconductivity and perform better than the binary Zr-H system. YZrH6 can maintain dynamic stability down to ambient pressure and keep a critical temperature (Tc) of 16 K. The stable YZrH18 and metastable Y3ZrH24 with high hydrogen content exhibit high Tc of 156 K and 185 K at 200 GPa, respectively. Further analysis shows that the phonon modes associated with H atoms contribute significantly to the electron-phonon coupling. The hydrogen content and the stoichiometric ratio of Y and Zr closely affect the density of states at the Fermi level, thereby affecting the superconductivity. Our work presents an important step toward understanding the superconductivity and stability of transition metal ternary hydrides.

6.
BMC Musculoskelet Disord ; 24(1): 932, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041019

RESUMO

INTRODUCTION: The purpose of this study was to evaluate the protective effects of cordymin on osteoporosis induced by hindlimb unloading(HLU) in rats and whether cordymin can prevent bone loss from HLU. MATERIALS AND METHODS: We employed the hindlimb suspension rats model to mimic physiological changes concomitant with space travel.The mechanical strength in the femoral neck,cancellous bone volume, gut microbiota structure,serum calcium and phosphorus contents, bone mineral content and bone mineral content can be changed after hindlimb unloading. Oral cordymin was administered for 4 weeks,cordymin treatment significantly increased the mechanical strength through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). RESULTS: Importantly, 16 S rRNA sequencing showed cordymin treatment regulated the various genera that were imbalanced in hindlimb unloading rats. At the same time,The plasma total calcium and inorganic phosphate concentrations in hindlimb unloading rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with cordymin. CONCLUSION: These data indicate that the cordymin might exert bone protective effects indirectly via modulating the complex relationship between gut microbiota, microelements and bone loss.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Ratos , Animais , Elevação dos Membros Posteriores/fisiologia , Cálcio , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Osso e Ossos/diagnóstico por imagem , Densidade Óssea/fisiologia
7.
Biomed Chromatogr ; 36(1): e5248, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34555192

RESUMO

Vanillic acid, a phenolic compound isolated from Angelica sinensis and green tea, exhibits excellent antioxidant and anti-inflammatory activities. In this study, a rapid and sensitive ultra-high-performance liquid chromatography tandem mass spectrometry method was established and validated for the determination of vanillic acid in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Chromatographic separation was performed on a Zorbax RRHD Eclipse Plus C18 column (2.1 × 100 mm, 1.8 µm) with gradient elution at a flow rate of 0.3 ml/min, using mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Vanillic acid and caffeic acid (internal standard, IS) were quantified by multiple reaction monitoring in negative ion mode. The method was fully validated according to the US Food and Drug Administration guidelines. The calibration curve was linear over the range of 2-1,000 ng/ml with a correlation coefficient of >0.99. The carryover, matrix effect, extraction recovery, dilution effect, intra- and interday precision and accuracy were within acceptable limits. The method was then applied to a pharmacokinetic study of vanillic acid in rats. After oral administration at doses of 2, 5 and 10 mg/kg, the plasma concentration reached peaks of 0.42 ± 0.09, 0.73 ± 0.21 and 0.92 ± 0.28 µg/ml at the time of 0.55-0.64 h, respectively. The oral bioavailability was calculated as 25.3-36.2% in rat plasma. The result provided pre-clinical information for further application of vanillic acid.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Ácido Vanílico/sangue , Ácido Vanílico/farmacocinética , Animais , Disponibilidade Biológica , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Ácido Vanílico/química
8.
Molecules ; 27(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35807527

RESUMO

Ent-abietane diterpenoids are the main active constituents of Euphorbia fischeriana. In the continuing search for new anti-breast cancer drugs, 11 ent-abietane diterpenoids (1-11) were isolated from E. fischeriana. The structures of these compounds were clearly elucidated on the basis of 1D and 2D NMR spectra as well as HRESIMS data. Among them, compound 1 was a novel compound, compound 10 was isolated from Euphorbia genus for the first time, compound 11 was firstly discovered from E. fischeriana. These compounds exhibited varying degrees of growth inhibition against the MCF-10A, MCF-7, ZR-75-1 and MDA-MB-231 cell lines in vitro. The experimental data obtained permit us to identify the roles of the epoxy group, hydroxyl group and acetoxyl group on their cytotoxic activities. Extraction is an important means for the isolation, identification, and application of valuable compounds from natural plants. To maximize yields of ent-abietane diterpenoids of E. fischeriana, 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A were selected as quality controls to optimize the salting-out-assisted liquid-liquid extraction (SALLE) by response surface methodology (RSM). The optimized conditions for SALLE were 0.47 g sodium dihydrogen phosphate, 5.5 mL acetonitrile and 4.5 mL water at pH 7.5. The experimental values of 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A (2.134, 0.529, 0.396, and 0.148 mg/g, respectively) were in agreement with the predicted values, thus demonstrating the appropriateness of the model.


Assuntos
Antineoplásicos Fitogênicos , Diterpenos , Euphorbia , Neoplasias , Abietanos/análise , Abietanos/farmacologia , Antineoplásicos Fitogênicos/química , Diterpenos/química , Euphorbia/química , Estrutura Molecular , Neoplasias/tratamento farmacológico , Raízes de Plantas/química
9.
Molecules ; 27(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36144545

RESUMO

The World Health Organization predicts that over the next several years, depression will become the most important mental health issue globally. Growing evidence shows that the flower buds of Hemerocallis citrina Baroni (H. citrina) possess antidepressant properties. In the search for new anti-depression drugs, a total of 15 phenylpropanoids and 22 flavonoids were isolated and identified based on spectral data (1D and 2D NMR, HR-ESI-MS, UV) from H. citrina. Among them, compound 8 was a novel compound, while compounds 1-4, 6, 9, 10, 15, 17, 24-26, 28, and 37 were isolated for the first time from Hemerocallis genus. To study the antidepressant activity of phenylpropanoids and flavonoids fractions from H. citrina, macroporous resin was used to enrich them under the guidance of UV characteristics. UHPLC-MS/MS was applied to identify the constituents of the enriched fractions. According to behavioral tests and biochemical analyses, it showed that phenylpropanoid and flavonoid fractions from H. citrina can improve the depressive-like mental state of chronic unpredictable mild stress (CUMS) rats. This might be accomplished by controlling the amounts of the inflammatory proteins IL-6, IL-1ß, and TNF-α in the hippocampus as well as corticosterone in the serum. Thus, the monomer compounds were tested for their anti-neuroinflammatory activity and their structure-activity relationship was discussed in further detail.


Assuntos
Hemerocallis , Animais , Antidepressivos/farmacologia , Corticosterona , Flavonoides/farmacologia , Hemerocallis/química , Interleucina-6 , Ratos , Estresse Psicológico/metabolismo , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
10.
Environ Dev Sustain ; : 1-25, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36124159

RESUMO

The government's development of eco-environmental policies can have a scientific foundation thanks to the fine particulate matter (PM2.5) medium- and long-term change forecast. This study develops a STRIPAT-Scenario analysis framework employing panel data from 11 cities in Zhejiang Province between 2006 and 2020 to predict the changing trend of PM2.5 concentrations under five alternative scenarios. The results reveal that: (1) urbanization development (P), economic development (A), technological innovation investment (T) and environmental regulation intensity have a significant inhibitory effect on PM2.5 concentration in Zhejiang Province, while industrial structure, industrial energy consumption and the number of motor vehicles (TR) have a significant increase on PM2.5 concentration. (2) Under any scenario, the PM2.5 concentration of 11 cities in Zhejiang Province can reach the constraint target set in the 14th Five-Year plan. The improvement in urban PM2.5 quality is most obviously impacted by the high-quality development scenario (S4). (3) Toward 2035, PM2.5 concentrations of 11 cities in Zhejiang Province can reach the National Class I level standard in most scenario models, among which Hangzhou, Jiaxing and Shaoxing are under high pressure to reduce emissions and are the key areas for PM2.5 management in Zhejiang Province. However, most cities cannot reach the 10 µg/m3 limit of WHO's AQG2005 version. Finally, this study makes recommendations for reducing PM2.5 in terms of enhancing industrial structure and funding science and technology innovation.

11.
Clin Orthop Relat Res ; 479(10): 2228-2235, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33787525

RESUMO

BACKGROUND: Teleradiology has become one of the most important approaches to virtual clinical diagnosis; its importance has only grown during the coronavirus 2019 pandemic. In developing countries, asking patients to take photographs of their images using a smartphone can facilitate the process and help keep its costs down. However, the images taken by patients with smartphones often are of poor quality, and there is no regulation or standard instruction about how to use smartphones to take photographs of medical examination images effectively. These problems limit the use of smartphones in remote diagnosis and treatment. QUESTIONS/PURPOSES: To formulate a set of guidelines for the most appropriate and effective use of smartphones to capture images (radiographs, CT images, and MR images), and to determine whether these guidelines are more effectively adopted by patients of differing ages and genders. METHODS: In this prospective study, a set of step-by-step instructions was created with the goal of helping patients take better smartphone photographs of orthopaedic diagnostic images for transfer to telemedicine services. Following the advice of surgeons, experts in smartphone technology, imaging experts, and suggestions from patients, the instructions were modified based on clinical experience and finalized with the goals of simplicity, clarity, and convenience. Potentially eligible patients were older than 18 years, had no cognitive impairment, and used smart phones. Based on that, 256 participants (patients or their relatives and friends) who visited the orthopaedic department of our hospital from June to October 2020 potentially qualified for this study. A total of 11% (29) declined to participate, leaving 89% (227) for analysis here. Their mean age was 36 ± 11 years, 50% were women (113 of 227), and the patient himself/herself represented in 34% (78 of 227) of participants while relatives or friends of patients made up 66% (149 of 227) of the group. In this study, the diagnoses included spinal stenosis (47% [107 of 227]), disc herniation without spinal stenosis (31% [71 of 227]), vertebral fractures (14% [32 of 227]), and other (7% [17 of 227]). Each study participant first took photographs of their original medical images based on their own knowledge of how to use the smartphone camera function; each participant then took pictures of their original images again after receiving our instructional guidance. Three senior spine surgeons (YZ, TQL, TCM) in our hospital analyzed, in a blinded manner, the instructed and uninstructed imaging files based on image clarity (the content of the image is complete, the text information in the image is clearly visible, there is neither reflection nor shadow in the image) and image position (it is not tilted, curled, inverted, or reversed). If either of these conditions was not satisfied, the picture quality was deemed unacceptable; two of three judges' votes determined the outcome. Interobserver reliability with kappa values for the three judges were 0.89 (YZ versus TQL), 0.92 (YZ versus TCM), and 0.90 (TQL versus TCM). RESULTS: In this study, the overall proportion of smartphone medical images deemed satisfactory increased from 40% (91 of 227) for uninstructed participants to 86% (196 of 227) for instructed participants (risk ratio 2.15 [95% CI 1.82 to 2.55]; p<0.001). The proportion of acceptable-quality images in different age groups improved after instruction, except for in patients aged 51 years or older (3 of 17 uninstructed participants versus 8 of 17 instructed participants; RR 2.67 [95% CI 0.85 to 8.37]; p = 0.07). The proportion of acceptable-quality images in both genders improved after instruction, but there was no difference between the genders. CONCLUSION: We believe our guidelines for patients who wish to take smartphone photographs of their medical images will decrease image transmission cost and facilitate orthopaedic telemedicine consultations. However, it appears that patients older than 50 years are more likely to have difficulty with this approach, and if so, they may benefit from more hands-on assistance from clinic staff or younger relatives or friends. The degree to which our findings are culture-specific should be verified by other studies in other settings, but on the face of it, there is little reason to believe our findings would not generalize to a reasonable degree. Other studies in more heterogeneous populations should also evaluate factors related to levels of educational attainment and wealth differences, but in the meantime, our findings can give clinical teams an idea of which patients may need a little extra assistance. LEVEL OF EVIDENCE: Level II, therapeutic study.


Assuntos
Diagnóstico por Imagem/normas , Fotografação/normas , Smartphone/normas , Telerradiologia/normas , Adulto , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2
12.
J Sep Sci ; 43(11): 2180-2192, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32133730

RESUMO

A novel and simple method was established for the extraction and determination of seven compounds in Anemarrhena asphodeloides Bge. using silica gel-based vortex-homogenized matrix solid-phase dispersion and ultra-high performance liquid chromatography quadrupole-time of-flight mass spectrometer. The conditions for the extraction were optimized. Silica gel was used as the dispersant, 50% methanol-water was selected as an elution solvent and the grinding time was 3 min. Compared with the traditional ultrasonic-assisted extraction, the developed method was rapid and efficient. In order to screen potential antioxidants, extract dealing with the optimized method was applied to a polyamide chromatography column and a D-101 macroporous resin column. Fr.2.2 showed the highest antioxidant activities with the most content of flavonoid. A total of 25 peaks were identified from the active fraction. A 2,2'-diphenyl-1-picrylhydrazyl ultra-high performance liquid chromatography coupled with mass spectrometry approach was adopted for the rapid and exact screening and identification of antioxidant compounds. It indicated that flavonoids exhibited potential antioxidant activities. The antioxidant activities of nine monomeric compounds in vivo were tested. Structure-activity relationships were discussed. Five flavonoids with the concentration of 500 µg/mL would reduce the oxidative stress of PC12 cells that were induced with 2,2'-azobis[2-methylpropionamidine] dihydrochloride.


Assuntos
Anemarrhena/química , Antioxidantes/análise , Flavonoides/análise , Extratos Vegetais/isolamento & purificação , Extração em Fase Sólida , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Animais , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Sílica Gel/química
14.
Chemistry ; 24(71): 18981-18987, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30252969

RESUMO

Protein glycosylation is the most complex post-translational modification process. More than 50 % of human cells proteins are glycosylated, whereas bacteria such as E. coli do not have this modification machinery. Indeed, the carbohydrate residues in natural proteins affect their folding, immunogenicity, and stability toward proteases, besides controlling biological properties and activities. It is therefore important to introduce such structural modification in bioengineered proteins lacking the presence of carbohydrate residues. This is not trivial as it requires reagents and conditions compatible with the protein's stability and reactivity. This work reports on the introduction of lactose moieties in two natural proteins, namely ubiquitin (Ub) and l-asparaginase II (ANSII). The synthetic route employed is based on the sulfur(VI) fluoride exchange (SuFEx) coupling of a lactose tethered arylfluorosulfate (Lact-Ar-OSO2 F) with the ϵ-NH2 group of lysine residues of the proteins. This metal-free click SuFEx reaction relies on the properties of the fluorosulfate employed, which is easily prepared in multigram scale from available precursors and reacts chemoselectively with the ϵ-NH2 group of lysine residues under mild conditions. Thus, iterative couplings of Lact-Ar-OSO2 F to Ub and ANSII, afforded multiple glycosylations of these proteins so that up to three and four Lact-Ar-OSO2 groups were introduced in Ub and ANSII, respectively, via the formation of a sulfamoyl (OSO2 -NH) linkage.

15.
Angew Chem Int Ed Engl ; 57(10): 2605-2610, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29276888

RESUMO

Sulfuryl fluoride, SO2 F2 , has been found to derivatize phenols in all kinds of environments, even those in highly functional molecules. We now report that a solid fluorosulfuryl imidazolium triflate salt delivers the same "F-SO2 +" fragment to Nu-H acceptor groups in the substrates. However, this triflate salt is a far more reactive fluorosulfurylating agent than SO2 F2 and displays selectivity preferences of its own. Moreover, the new azolium triflate reagent reacts once with primary amines and anilines before the reaction stops. On the other hand, with triethylamine and two equivalents of the "F-SO2 +" donor present, it proceeds on to the bis(fluorosulfuryl)imides in good yield-two important conversions that we have never seen with sulfuryl fluoride as the electrophile.

17.
Biomed Chromatogr ; 29(9): 1297-303, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25620053

RESUMO

A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats.


Assuntos
Benzofuranos/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Ligusticum/química , Transtornos de Enxaqueca/tratamento farmacológico , Administração Oral , Animais , Benzofuranos/administração & dosagem , Benzofuranos/farmacocinética , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacocinética , Humanos , Masculino , Transtornos de Enxaqueca/sangue , Ratos , Ratos Sprague-Dawley , Rizoma , Espectrometria de Massas em Tandem
18.
J Orthop Surg Res ; 19(1): 265, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671500

RESUMO

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.


Assuntos
Necrose da Cabeça do Fêmur , Glucocorticoides , Microvasos , Humanos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etiologia , Microvasos/patologia , Glucocorticoides/efeitos adversos , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/patologia , Microcirculação , Neovascularização Patológica/etiologia
19.
Pathol Res Pract ; 257: 155312, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663177

RESUMO

Current treatments for orthopaedic illnesses frequently result in poor prognosis, treatment failure, numerous relapses, and other unpleasant outcomes that have a significant impact on patients' quality of life. Cell-free therapy has emerged as one of the most promising options in recent decades for improving the status quo. As a result, using exosomes produced from various cells to modulate ferroptosis has been proposed as a therapeutic method for the condition. Exosomes are extracellular vesicles that secrete various bioactive chemicals that influence disease treatment and play a role in the genesis and progression of orthopaedic illnesses. Ferroptosis is a recently defined kind of controlled cell death typified by large iron ion buildup and lipid peroxidation. An increasing number of studies indicate that ferroptosis plays a significant role in orthopaedic illnesses. Exosomes, as intercellular information transfer channels, have been found to play a significant role in the regulation of ferroptosis processes. Furthermore, accumulating research suggests that exosomes can influence the course of many diseases by regulating ferroptosis in injured cells. In order to better understand the processes by which exosomes govern ferroptosis in the therapy of orthopaedic illnesses. This review discusses the biogenesis, secretion, and uptake of exosomes, as well as the mechanisms of ferroptosis and exosomes in the therapy of orthopaedic illnesses. It focuses on recent research advances and exosome mechanisms in regulating iron death for the therapy of orthopaedic illnesses. The present state of review conducted both domestically and internationally is elucidated and anticipated as a viable avenue for future therapy in the field of orthopaedics.


Assuntos
Exossomos , Ferroptose , Ferroptose/fisiologia , Humanos , Exossomos/metabolismo , Animais , Ferro/metabolismo
20.
J Orthop Surg Res ; 18(1): 352, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37170290

RESUMO

OBJECTIVE: To assess the clinical efficacy of three different surgical approaches in the treatment of thoracolumbar tuberculosis. METHODS: A total of 138 patients with thoracolumbar tuberculosis treated by open surgery were retrospectively analyzed. The surgical methods were divided into anterior, posterior and anterior-posterior combined. The hospital stays, amount of bleeding, operative time, preoperative, postoperative and last follow-up ESR, CRP, Frankel score, ODI, VAS, correction and loss rate of kyphosis, fusion rate and complications were recorded and analyzed. RESULTS: The average follow-up was 66 months. The average hospital stay, operative time and amount of bleeding of the anterior-posterior combined group were higher than other groups (P < 0.05). ESR and CRP of all patients were reduced postoperatively (P < 0.05). No significant difference among the three groups was found in the postoperative correction angle of kyphosis (P < 0.05), while the pre- and postoperative Cobb angle as well as correction rate had significant differences. The posterior approach could achieve better correction, and the loss of correction was more in the anterior group, 40.9 percent of patients performed correction loss. The Frankel score, VAS and ODI were significantly reduced among the three groups, and the incidence rate of complications of the anterior approach was lower than the other groups, with a significant difference (P < 0.05). CONCLUSION: The anterior approach has more advantages and fewer complications, which is supposed to give preference to and could not be replaced by the posterior and anterior-posterior combined approach.


Assuntos
Cifose , Fusão Vertebral , Tuberculose da Coluna Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Cifose/cirurgia , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/cirurgia , Tuberculose da Coluna Vertebral/complicações , Fusão Vertebral/métodos
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