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1.
Zhongguo Zhong Yao Za Zhi ; 49(3): 607-617, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621864

RESUMO

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.


Assuntos
Medicamentos de Ervas Chinesas , Excipientes , Excipientes/química , Medicina Tradicional Chinesa , Água/química , Medicamentos de Ervas Chinesas/química
2.
Zhongguo Zhong Yao Za Zhi ; 49(3): 634-643, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621867

RESUMO

This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(G″), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and G″ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.


Assuntos
Medicina Tradicional Chinesa , Prescrições , Pós , Viscosidade , Reologia
3.
Immun Inflamm Dis ; 12(2): e1172, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38358044

RESUMO

INTRODUCTION: Nuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC. METHODS: We performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin-forming cells (HaCaT) and human cSCC cells (A431, Colo-16, SCL-1, SCL-2, and HSC-5). Stable A431 and SCL-2 cell lines consisting of sh-RNA-NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/ß-catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK-8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown. RESULTS: NR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/ß-catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin. CONCLUSION: NR5A2 plays a crucial role in the progression of cSCC, and the Wnt/ß-catenin signaling pathway may be involved in the regulation of NR5A2-mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , beta Catenina/genética , beta Catenina/metabolismo , Cisplatino/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Linhagem Celular Tumoral , Receptores Citoplasmáticos e Nucleares
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010296

RESUMO

OBJECTIVE@#To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism.@*METHODS@#B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR.@*RESULTS@#In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells.@*CONCLUSIONS@#Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.


Assuntos
Camundongos , Animais , Alocasia/metabolismo , Sistema de Sinalização das MAP Quinases , Caspase 3/metabolismo , Apoptose , RNA Mensageiro/metabolismo
5.
International Eye Science ; (12): 77-81, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1003510

RESUMO

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1003426

RESUMO

Diabetic ulcer (DU) wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing, and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment, long treatment process, and high morbidity and mortality. Therefore, how to help the rapid healing of DU wounds, reduce the disability rate and mortality rate, protect limb function, and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex, mainly including microcirculation disorder, peripheral neuropathy, inflammation and infection, and excessive apoptosis of cells, involving physiological processes such as wound inflammation, granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Wnt/β-catenin, nuclear factor-κB (NF-κB), Notch, nuclear factor E2-related factor 2 (Nrf2), transforming growth factor-β (TGF-β)/Smad, and other signaling pathways, regulate abnormal glucose metabolism, improve microcirculation, inhibit inflammation and oxidative stress, regulate cell proliferation and excessive apoptosis, and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine (TCM) syndrome differentiation and internal and external treatment. Therefore, this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds, aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

7.
Acta Anatomica Sinica ; (6): 88-97, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015151

RESUMO

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

8.
Chinese Pharmacological Bulletin ; (12): 114-158, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013615

RESUMO

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013378

RESUMO

ObjectiveTo explore the effect of brain-computer interface (BCI) based on visual, auditory and motor feedback combined with transcranial direct current stimulation (tDCS) on upper limb function in stroke patients. MethodsFrom March to October, 2023, 45 stroke inpatients in Xuzhou Rehabilitation Hospital and Xuzhou Central Hospital were divided into BCI group (n = 15), tDCS group (n = 15) and combined group (n = 15) randomly. All the groups received routine rehabilitation, while BCI group received BCI training, tDCS group received tDCS, while the combined group received tDCS and followed by BCI training immediately, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT), modified Barthel Index (MBI) and delta-alpha ratio (DAR) and power ratio index (PRI) of electroencephalogram before and after treatment. ResultsThe scores of FMA-UE, ARAT and MBI increased in all the groups after treatment (|t| > 5.350, P < 0.001), and all these indexes were the best in the combined group (F > 3.366, P < 0.05); while DAR and PRI decreased in all the groups (|t| > 2.208 , P < 0.05), they were the best in the combined group (F > 5.224, P < 0.01). ConclusionBCI based on visual, auditory and motor feedback combined with tDCS can further improve the motor function of upper limbs and the activities of daily living of stroke patients.

10.
International Eye Science ; (12): 589-595, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012827

RESUMO

N6-methyladenosine(m6A), the most common, abundant, and conserved RNA modification in eukaryotic cells, regulates RNA splicing, stability, output, degradation and translation through m6A methyltransferase, m6A demethylase, and m6A methylated binding proteins. Recent studies have found that abnormal m6A methylation may mediate a variety of pathological processes in eyes and participate in the occurrence and development of metabolic, inflammatory, degenerative ocular diseases and ocular tumors, such as diabetic retinopathy, cataract, age-related macular degeneration and uveal melanoma. This review aims to summarize the roles of m6A methylation modification in ocular cells and ocular diseases, elucidate the potential molecular mechanisms of m6A methylation in ocular diseases, so as to encourage innovative approaches in the treatment of these ocular diseases.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009891

RESUMO

OBJECTIVES@#To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD).@*METHODS@#A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis.@*RESULTS@#The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05).@*CONCLUSIONS@#There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.


Assuntos
Criança , Masculino , Humanos , Doença de Crohn/complicações , Estudos Retrospectivos , Prognóstico , Infliximab/uso terapêutico , Fístula Retal/terapia
12.
Zool Res ; 44(6): 1026-1038, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37804114

RESUMO

Quantification of behaviors in macaques provides crucial support for various scientific disciplines, including pharmacology, neuroscience, and ethology. Despite recent advancements in the analysis of macaque behavior, research on multi-label behavior detection in socially housed macaques, including consideration of interactions among them, remains scarce. Given the lack of relevant approaches and datasets, we developed the Behavior-Aware Relation Network (BARN) for multi-label behavior detection of socially housed macaques. Our approach models the relationship of behavioral similarity between macaques, guided by a behavior-aware module and novel behavior classifier, which is suitable for multi-label classification. We also constructed a behavior dataset of rhesus macaques using ordinary RGB cameras mounted outside their cages. The dataset included 65 913 labels for 19 behaviors and 60 367 proposals, including identities and locations of the macaques. Experimental results showed that BARN significantly improved the baseline SlowFast network and outperformed existing relation networks. In conclusion, we successfully achieved multi-label behavior detection of socially housed macaques with both economic efficiency and high accuracy.


Assuntos
Comportamento Animal , Animais , Macaca mulatta
13.
Nat Prod Res ; : 1-11, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37378495

RESUMO

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense. With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a, 4b, 5a and 5b) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a, 5b, ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 µg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 µg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines.

14.
Front Immunol ; 14: 1139599, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006256

RESUMO

Background: Histone acetylation-related lncRNAs (HARlncRNAs) play significant roles in various cancers, but their impact on lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop a new HARlncRNA-based prognostic model for LUAD and to explore its potential biological mechanisms. Methods: We identified 77 histone acetylation genes based on previous studies. HARlncRNAs related to prognosis were screened by co-expression, univariate and multivariate analyses, and least absolute shrinkage selection operator regression (LASSO). Afterward, a prognostic model was established based on the screened HARlncRNAs. We analysed the relationship between the model and immune cell infiltration characteristics, immune checkpoint molecule expression, drug sensitivity, and tumour mutational burden (TMB). Finally, the entire sample was divided into three clusters to further distinguish between hot and cold tumours. Results: A seven-HARlncRNA-based prognostic model was established for LUAD. The area under the curve (AUC) of the risk score was the highest among all the analysed prognostic factors, indicating the accuracy and robustness of the model. The patients in the high-risk group were predicted to be more sensitive to chemotherapeutic, targeted, and immunotherapeutic drugs. It was worth noting that clusters could effectively identify hot and cold tumours. In our study, clusters 1 and 3 were considered hot tumours that were more sensitive to immunotherapy drugs. Conclusion: We developed a risk-scoring model based on seven prognostic HARlncRNAs that promises to be a new tool for evaluating the prognosis and efficacy of immunotherapy in patients with LUAD.


Assuntos
Adenocarcinoma , Histonas , Humanos , Acetilação , Biomarcadores , Prognóstico , Imunidade , Pulmão
15.
Zhongguo Zhong Yao Za Zhi ; 48(3): 588-595, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872221

RESUMO

Lozenge is one of the traditional dosage forms of Chinese medicine. It has been recorded in traditional Chinese medical classics of all dynasties since the Eastern Han Dynasty and has been developing and evolving continuously. The unique pharmaceutical methods and application scope are the driving force of its emergence, existence, and development. Up to now, lozenge has been included in the Chinese Pharmacopoeia as an independent dosage form. Lozenge has been endowed with new meaning by modern Chinese medicine pharmaceutics, which is worth tracing origin and exploring value. The present study reviewed the origin and development of lozenge, compared lozenge with other similar dosage forms, analyzed the characteristics of modern and ancient dosage forms of lozenge, and discussed the development prospect and potential of lozenge in combination with the demand development of modern Chinese medicine preparation, so as to provide references for expanding the modern application of lozenge.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional do Leste Asiático , Biofarmácia , Comprimidos
16.
Clin Cardiol ; 46(5): 512-520, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36896666

RESUMO

OBJECTIVE: Peripheral arterial disease (PAD) affects a large population and is associated with various adverse clinical outcomes. Lipoprotein(a) has proatherogenic properties and is associated with PAD incidence and severity. The aim of this study is to explore the association between LP(a) and PAD in coronary artery bypass grafting (CABG) patients. METHODS: A total of 1001 patients were included and divided into two groups: low Lp(a) group [LP(a) < 30 mg/dL] and high Lp(a) group [LP(a) ≥ 30 mg/dL]. A comparison of PAD incidence diagnosed by ultrasound was made between the groups. Multivariate logistic regression was conducted to explore the risk factors for PAD. During the analysis, the influence of diabetes mellitus (DM) and gender on LP(a) serum level was taken into consideration. RESULTS: DM history (odds ratio [OR], 2.330, p = .000 for males; OR, 2.499, p = .002 for females) and age (OR, 1.101, p = .000 for males; OR, 1.071, p = .001 for females) were risk factors for PAD. LP(a) ≥ 30 mg/dL was a risk factor for PAD only in female patients (OR, 2.589, p = .003), while smoking history was a risk factor only in male patients (OR, 1.928, p = .000). LP(a) level was not associated with PAD severity in DM patients of both gender. As for female patients without DM, PAD was more severe in the high LP(a) group. CONCLUSIONS: In CABG patients, DM history and age were risk factors for PAD. But a high level of LP(a) was a significant risk factor only in female patients. In addition, we are the first to propose a gender deviation in the correlation between LP(a) serum level and severity of PAD diagnosed by ultrasound.


Assuntos
Doença da Artéria Coronariana , Doença Arterial Periférica , Humanos , Masculino , Feminino , Lipoproteína(a) , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , Fatores de Risco , Modelos Logísticos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/cirurgia
17.
Front Immunol ; 14: 1122352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875059

RESUMO

The morbidity and mortality of lung cancer are increasing, seriously threatening human health and life. Non-small cell lung cancer (NSCLC) has an insidious onset and is not easy to be diagnosed in its early stage. Distant metastasis often occurs and the prognosis is poor. Radiotherapy (RT) combined with immunotherapy, especially with immune checkpoint inhibitors (ICIs), has become the focus of research in NSCLC. The efficacy of immunoradiotherapy (iRT) is promising, but further optimization is necessary. DNA methylation has been involved in immune escape and radioresistance, and becomes a game changer in iRT. In this review, we focused on the regulation of DNA methylation on ICIs treatment resistance and radioresistance in NSCLC and elucidated the potential synergistic effects of DNA methyltransferases inhibitors (DNMTis) with iRT. Taken together, we outlined evidence suggesting that a combination of DNMTis, RT, and immunotherapy could be a promising treatment strategy to improve NSCLC outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estudos de Viabilidade , Imunoterapia , Metiltransferases , DNA
18.
J Biomol Struct Dyn ; 41(21): 12372-12386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656084

RESUMO

SUMOylation regulates various cellular process and SENP1 (SUMO-specific protease 1) serves as a SUMO (small ubiquitin-related modifier) specific protease that participates in the SUMO cycle. Given its extensive influences on metabolic activities, SENP1 has gained more and more attentions in clinical treatments. However, there remains a question on why does the SENP1 prefer to process SUMO1 rather than SUMO2. Here, we performed molecular dynamics simulations of SENP1-SUMO1, SENP1-SUMO2, and apo SENP1 systems and observed distinct conformational dynamics in the upper half of the clamp and the three loops in the catalytic center of the SENP1. Principal component analysis revealed that the most prominent canonical variable represented the spatial distribution of the upper half of the clamp, while the openness of the cleft was closely related to the catalytic ability of SENP1. Further analysis of the SENP1-SUMO interactions revealed that the extensive and strong interactions between the SENP1 and SUMO1 were both in the interface of the upper half region and the catalytic center. Dynamic cross-correlation matrix analysis demonstrated that the inter-residue correlations in the SUMO1 system was much stronger, especially in the two essential regions belonging to the upper and lower half of cleft. Based on these observations, we proposed an allosteric propagation model and further testified it using the community analysis. These results revealed the propagation pathway of allosteric communication that contributed to the substrate discrimination of SENP1 upon SUMO1 and SUMO2.Communicated by Ramaswamy H. Sarma.


Assuntos
Cisteína Endopeptidases , Proteína SUMO-1 , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina , Simulação de Dinâmica Molecular , Ubiquitina , Cisteína Endopeptidases/química , Proteína SUMO-1/química , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/química
19.
Immunotherapy ; 15(2): 71-75, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36628567

RESUMO

Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.


In clinical practice, symptoms associated with abnormal coagulation or fibrinolytic function in malignant tumors are known as Trousseau's syndrome. Its main clinical features include cerebral infarction, myocardial infarction, peripheral arterial embolism, etc. Trousseau's syndrome is a relatively rare reported event in immune checkpoint inhibitors (ICIs)-related clinical studies, mostly occurring in the early period of ICI therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab, one of the ICI agents, maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. This patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticoagulantes/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Trombocitopenia/induzido quimicamente
20.
J Adv Res ; 51: 1-11, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494064

RESUMO

INTRODUCTION: The excessive dosage of pesticides required for agronomic reality results in growing contamination of pesticide residues in environment, thus bringing high risks to crop production and human health. OBJECTIVES: This study aims to unveil a novel mechanism for catabolism of two pesticides MTR and FSA facilitated by an uncharacterized Phase II reaction enzyme termed acetyltransferase-1 (ACE1) in rice and to make assessment of its potential for bioremediation to minimize the risks to crop production and food safety. METHODS: We developed genetically improved cultivars overexpressing OsACE1 (OE) and knockout mutant lines by CRISPR-Cas9 technology to identify the MTR and FSA detoxic and metabolic functions and characterized their metabolites and conjugates by HPLC-LTQ-MS/MS. RESULTS: OsACE1 overexpression conferred rice resistance to toxicity of MTR/FSA compared to wild-type, manifested by improved plant elongation and biomass, attenuated cellular injury, and increased chlorophyll accumulation. The OE plants accumulated significantly less parent MTR/FSA and more degradative metabolites, and removed MTR/FSA from their growth medium by 1.38 and 1.61 folds over the wild-type. In contrast, knocking out OsACE1 led to compromised growth fitness and intensified toxic symptoms under MTR/FSA stress and accumulation of more toxic MTR and FSA in rice. The reduced metabolites of MTR and FSA detected in the Cas9 plants suggest the impaired capability of OsACE1 function. CONCLUSIONS: These results signified that OsACE1 expression is required for detoxifying the two poisoning chemicals in rice and plays a critical role in accelerating breakdown of the pesticides mainly through Phase II reaction mechanism pathways.


Assuntos
Oryza , Praguicidas , Humanos , Oryza/genética , Oryza/metabolismo , Espectrometria de Massas em Tandem , Acetiltransferases/metabolismo , Praguicidas/metabolismo
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