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1.
Artigo em Inglês | MEDLINE | ID: mdl-38696085

RESUMO

PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.

2.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5068-5077, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802849

RESUMO

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.


Assuntos
Isoflavonas , Micelas , Ratos , Animais , Distribuição Tecidual , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ratos Endogâmicos SHR , Isoflavonas/farmacologia
3.
Front Pharmacol ; 14: 1236656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601055

RESUMO

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

4.
Zhongguo Zhong Yao Za Zhi ; 48(3): 579-587, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872220

RESUMO

Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.


Assuntos
Pontos de Acupuntura , Meridianos , Humanos , Disponibilidade Biológica , Fumigação , Medicina Tradicional Chinesa
5.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6526-6532, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38212010

RESUMO

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
6.
Biomedicines ; 10(7)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35884843

RESUMO

Immune checkpoint inhibitors (ICI) for early-stage non-small cell lung cancer (NSCLC) have been approved to improve outcomes and reduce recurrence. Biomarkers for patient selection are needed. In this paper, we proposed an inflammasome-based risk score (IRS) system for prognosis and prediction of ICI response for early-stage NSCLC. Cox regression analysis was used to identify significant genes (from 141 core inflammasome genes) for overall survival (OS) in a microarray discovery cohort (n = 467). IRS was established and independently validated by other datasets (n = 1320). We evaluated the inflammasome signaling steps based on five gene sets, which were IL1B-, CASP-1-, IL18-, GSDMD-, and inflammasome-regulated genes. Gene set enrichment analysis, the Kaplan-Meier curve, receiver operator characteristic with area under curve (AUC) analysis, and advanced bioinformatic tools were used to confirm the ability of IRS in prognosis and classification of patients into ICI responders and non-responders. A 30-gene IRS was developed, and it indicated good risk stratification at 10-year OS (AUC = 0.726). Patients were stratified into high- and low-risk groups based on optimal cutoff points, and high-risk IRS had significantly poorer OS and relapse-free survival. In addition, the high-risk group was characterized by an inflamed immunophenotype and higher proportion of ICI responders. Furthermore, expression of SLAMF8 was the key gene in IRS and indicated good correlation with biomarkers associated with immunotherapy. It could serve as a therapeutic target in the clinical setting of immunotherapy.

7.
Angew Chem Int Ed Engl ; 61(28): e202204661, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35445780

RESUMO

Oxidizing CH4 into liquid products with O2 under mild conditions still mainly relies on metal catalysis. We prepared a series of sulfone-modified conjugated organic polymers and found that the catalyst with proper SVI content (0.10) could drive O2 →H2 O2 →⋅OH to oxidize CH4 into CH3 OH and HCOOH directly and efficiently at room temperature under light irradiation. Experimental results showed that after 4 h reaction, decomposition rate and residual amounts of H2 O2 were 81.21 % and 4.83 mmol gcat -1 respectively, and CH4 conversion rate was 22.81 %. Mechanism studies revealed that illumination could induce the homolytic dissociation of S=O bonds on catalyst to produce oxygen and sulfur radicals, where the ⋅O could adsorb and activate CH4 , and the ⋅S could supply electrons for 1 O2 to generate H2 O2 and then for decomposing the H2 O2 into ⋅OH timely to oxidize CH4 . This research provided a novel organic catalysis approach for oxygen activation and utilization.

8.
Mol Ther ; 30(7): 2568-2583, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35351656

RESUMO

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Células-Tronco Mesenquimais , Proteínas Proto-Oncogênicas c-fos/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Enzima Desubiquitinante CYLD/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/metabolismo , Radiação Ionizante , Enzimas de Conjugação de Ubiquitina/metabolismo
9.
Pharmaceutics ; 13(6)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070708

RESUMO

It is necessary to prepare porous lactose in order to improve the dissolution behavior of insoluble active ingredient. In this study, polyvinylpyrrolidone K30 (PVP K30) was firstly utilized as a templating agent with different use levels in preparing porous lactose. Then, the physical properties were profoundly characterized. Finally, the porous lactose was also employed as a health functional food/drug carrier to explore the effect on the dissolution behavior of curcumin. The results confirmed that (i) porous lactose was successfully prepared using PVP K30 as templating agent; (ii) PVP K30 significantly improved the yield of lactose in the spray drying; (iii) the improved powder properties of porous lactose were more conducive to the downstream operating process for the preparation of health functional food or drug; and (iv) the porous lactose significantly improved the dissolution behavior of curcumin. Therefore, the results obtained are beneficial to boosting the development of porous materials.

10.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1311-1331, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787127

RESUMO

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.


Assuntos
Isoflavonas , Pueraria , China , Isoflavonas/farmacologia , Japão , Raízes de Plantas , República da Coreia , Tailândia
11.
Org Lett ; 22(15): 5861-5865, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32644806

RESUMO

A gold-catalyzed dearomatization reaction of ß-naphthol derivatives via intramolecular hydroalkylation of alkynes is described. In the presence of 5 mol % Au complex, various spironaphthalenones were obtained from α-tethered alkyne ß-naphthols in good to excellent yields (76-99%) under open-flask conditions.

12.
Pharmaceutics ; 12(3)2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32131425

RESUMO

In this paper, as an active ingredient, puerarin chitosan nanoparticles (Pur-CS/TPP-NPs) are prepared by an ionic gelation method. The chitosan (CS) concentration, pH of the CS solution, sodium tripolyphosphate (TPP) concentration, stirring speed, stirring time, ultrasonic power, and dosage are used as single factors for investigation, and the encapsulation efficiency, drug loading capacity, particle size, and polydispersity index (PDI) are used as indicators for investigation. The optimal prescription is determined using the Box-Behnken effect surface design method. The characterization of the best formulation, which is determined via an in vitro release assay and liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis methods, is used here for pharmacokinetic studies. An in situ single-pass intestinal perfusion model is used to investigate drug absorption in the intestine. After characterization, the morphologies of the nanoparticles are intact. It can be seen from the in vitro release experiments that the equation fitted by the nanoparticles is the Higuchi model, the nanoparticle release process is very stable and without sudden release, indicating that the nanoparticles are well-released in vitro. The pharmacokinetic results and the in situ single-pass intestinal perfusion model study show that the bioavailability and absorption of Pur-CS/TPP-NPs were significantly higher than Pur. Thus, all the results show that the prepared nanoparticles can significantly improve the bioavailability of Pur, and we hope to lay the foundation for the development of new products of Pur.

13.
Sci Rep ; 10(1): 3104, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080265

RESUMO

In Taiwan, patients with pulmonary hypertension (PH) related to chronic obstructive pulmonary disease (COPD) are most common PH population (group 3). However, efficacy of medical treatments and optimal prevention methods in this group remain uncertain. Statins such as indirect RhoA/Rho-kinase inhibitors influence one of key signalling pathways that promote PH onset. In this study, we explored protective effects of statins against PH in COPD patients using database from Taiwan National Health Insurance programme from 2002 to 2017. The main outcome was the risk of PH. The Cox proportional-hazards model and the Fine and Gray model were used to adjust covariate and competing risks to estimate the subdistribution hazard ratios (sHRs). 553,617 newly diagnosed COPD patients were stratified by statin users (n = 41,168) and statin nonusers (n = 512,449). After 1:1 propensity score matching of statin users (n = 41,163), and 41,163 statin nonusers were included for outcome analysis. Statin users had a 22% lower risk of PH than nonusers (sHR: 0.78, 95% confidence interval: 0.65-0.94). During subgroup analysis, taking higher daily doses and for a longer duration displayed a more significantly reduced risk of PH (both P for trend <0.001). Statins may have a protective effect against PH that is dose- and time-dependent.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão Pulmonar/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Proliferação de Células , Bases de Dados Factuais , Feminino , Humanos , Hipertensão Pulmonar/complicações , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Pontuação de Propensão , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Risco , Transdução de Sinais , Taiwan/epidemiologia
14.
RSC Adv ; 10(62): 38024-38032, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-35515147

RESUMO

In this work, a series of Cu(ii)-doped Bi2WO6 nanomaterials with good photo-response properties were facile synthesized and used to obtain efficient peroxymonosulfate (PMS) activation activity for norfloxacin (NOF) removal under visible LED light irradiation. It was found that Cu-Bi2WO6 presents superior catalytic performance for NOF degradation in comparison with pristine Bi2WO6, attributed to the partial substitution of Bi3+ by Cu ions. Moreover, the effects of experimental conditions were carefully investigated, including PMS concentration, catalyst dosage and initial pH, and the experimental data fitted well with the pseudo-first-order model. Experimental results implied that there was a synergic effect of visible LED light energy and the sulfate radical (SR)-Fenton reaction. Additionally, the 5Cu-Bi2WO6 nanomaterial presented the best degradation efficiency of 89.27% and exhibited high NOF degradation in 5 cycles with limited Cu leaching. Furthermore, EPR and radical quenching experiments were performed to identify the reactive oxygen species presented in the SR-photo-Fenton reaction. Finally, the major degradation intermediates of NOF were detected, and a possible degradation pathway was given. Thus, a mechanism of the significant photocatalytic activity enhancement by copper doping of the Bi2WO6 catalyst was proposed.

15.
Front Pharmacol ; 11: 613761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33510638

RESUMO

Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk for pulmonary hypertension (PH). The aim of our study was to investigate the benefit of statins for PH in patients with COPD. Methods: The study enrolled 23 million individuals from Taiwan's population database from January 1, 2002, to December 31, 2017. COPD patients who met the inclusion criteria were enrolled, and patients with lung cancer, less than one year of observation, specific drug therapy for PH and lung transplantation were excluded. Results: A total of 643,131 COPD patients were included in the study, and only 12,308 patients developed PH during follow-up. Based on the inclusion and exclusion criteria, 8,577 PH patients were included in the cohort of patients with PH related to COPD for analysis. According to the definition of statin exposure, the final study population had 1,487 statin users and 7,090 statin non-users. The statin user group had a lower mortality related to PH than the non-user group (3.87 vs. 5.55 per 100 person-years, p < 0.001). The mortality rate for PH in the multivariate analysis (aHR = 0.78, 95% CI = 0.62-0.98, p = 0.046) was significantly lower for statin users than for non-users. Conclusion: Statins seem to benefit patients with PH and COPD.

16.
Org Lett ; 22(4): 1233-1238, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31789039

RESUMO

A gold-catalyzed dearomatization reaction of indole derivatives was realized in the presence of JohnPhosAuCl/AgOMs to afford a series of spiroindolenines in excellent yields (≤99%). In addition, when the Hantzsch ester was used as the hydrogen transfer reagent, various spiroindolines were obtained in a cascade fashion starting from readily available indole derivatives in modest to good yields (≤79%). Both reactions feature readily available substrates, mild conditions, and good functional group tolerance.


Assuntos
Ouro/química , Indóis/química , Indóis/síntese química , Compostos de Espiro/síntese química , Catálise , Estrutura Molecular , Compostos de Espiro/química , Estereoisomerismo
17.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4134-4141, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872690

RESUMO

Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.


Assuntos
Isoflavonas , Pueraria , Administração Oral , Biofarmácia
18.
Mol Cell Biol ; 38(13)2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29661920

RESUMO

DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive. Here, we show that Dhtkd1-/- mice mimic the major aspects of CMT2 phenotypes, characterized by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity. Moreover, DHTKD1 deficiency causes severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies revealed that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion. Subsequently, elevated insulin regulates myelin protein zero (Mpz) transcription in Schwann cells via upregulating the expression of early growth response 2 (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2-AAA-fed mice do reproduce phenotypes similar to CMT2Q phenotypes. In conclusion, we have demonstrated that loss of DHTKD1 causes CMT2Q-like phenotypes through dysregulation of Mpz mRNA and protein zero (P0) which are closely associated with elevated DHTKD1 substrate and insulin levels. These findings further indicate an important role of metabolic disorders in addition to mitochondrial insufficiency in the pathogenesis of peripheral neuropathies.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Cetona Oxirredutases/deficiência , Cetona Oxirredutases/genética , Ácido 2-Aminoadípico/metabolismo , Adipatos/metabolismo , Animais , Doença de Charcot-Marie-Tooth/fisiopatologia , Códon sem Sentido , Modelos Animais de Doenças , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Humanos , Insulina/metabolismo , Complexo Cetoglutarato Desidrogenase , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína P0 da Mielina/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Condução Nervosa , Fenótipo , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
19.
Molecules ; 22(12)2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29186044

RESUMO

Given the importance of heterocycle indole derivatives, much effort has been directed toward the development of methods for functionalization of the indole nucleus at N1 and C3 sites. Moreover, the platinum-catalyzed allyation of nucleophiles was an established and efficient way, which has been applied to medicinal and organic chemistry. In our research, the platinum-catalyzed 2,3-disubstitued indoles with allylic acetates was investigated under different conditions. Herein, we established a simple, convenient, and efficient method, which afforded high yield of allylated indoles.


Assuntos
Acetatos/química , Compostos Alílicos/química , Indóis/química , Platina/química , Catálise , Estrutura Molecular
20.
J Vis Surg ; 3: 138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29078698

RESUMO

BACKGROUND: Pulmonary segmentectomy can be an oncologic equivalent of lobectomy for small non-small cell lung cancer. Uniportal video-assisted thoracoscopic surgery (VATS) has recently showed favorable surgical outcomes, but remains technical demanding, especially in a complex procedure like anatomic segmentectomy. This manuscript demonstrates the surgical techniques for uniportal VATS segmentectomies with the assistance of additional needlescopic instruments. METHODS: Data of 22 consecutive patients who underwent 24 needlescopic-assisted uniportal VATS segmentectomies between December 2016 and June 2017 was analyzed. RESULTS: There were 12 uni-segmentectomies, 10 bi-segmentectomies, and 2 tri-segmentectomies. The mean operation time was 178.3 minutes. The mean duration of chest tube drainage was 5.2 days, and the mean duration of hospital stay was 7.4 days. There were two episodes of major bleeding and one case that required conversion to lobectomy. CONCLUSIONS: Under the assistance of additional needlescopic instruments, segmentectomy can be performed more easily and safely with uniportal VATS.

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