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1.
Sci Rep ; 14(1): 153, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168479

RESUMO

Mycoplasma pneumoniae pneumonia (MPP) often overlaps with the clinical manifestations and chest imaging manifestations of other types of community-acquired pneumonia (CAP). We retrospectively analyzed the clinical and imaging data of a group of patients with CAP, summarized their clinical and imaging characteristics, and discussed the diagnostic significance of their certain HRCT findings. The HRCT findings of CAP researched in our study included tree-in-bud sign (TIB), ground-glass opacity (GGO), tree fog sign (TIB + GGO), bronchial wall thickening, air-bronchogram, pleural effusion and cavity. The HRCT findings of all cases were analyzed. Among the 200 cases of MPP, 174 cases showed the TIB, 193 showed the GGO, 175 showed the tree fog sign, 181 lacked air-bronchogram. In case taking the tree fog sign and lack of air-bronchogram simultaneously as an index to distinguish MPP from OCAP, the sensitivity was 87.5%, the specificity was 97.5%, the accuracy was 92.5%. This study showed that that specific HRCT findings could be used to distinguish MPP from OCAP. The combined HRCT findings including the tree fog sign and lacked air-bronchogram simultaneously would contribute to a more accurate diagnosis of MPP.


Assuntos
Infecções Comunitárias Adquiridas , Derrame Pleural , Pneumonia por Mycoplasma , Adulto , Humanos , Pneumonia por Mycoplasma/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pandemias , Pulmão
2.
J Minim Access Surg ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37843162

RESUMO

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

3.
Multimed Tools Appl ; 82(15): 22651-22667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778717

RESUMO

CT diagnosis has been widely used in clinic because of its special diagnostic value. The image resolution of CT imaging system is constrained by X-ray focus size, detector element spacing, reconstruction algorithm and other factors, which makes the generated CT image have some problems, such as low contrast, insufficient high-frequency information, poor perceptual quality and so on. To solve the above problems, a super-resolution reconstruction method of CT image based on multi-scale attention mechanism is proposed. First, use a 3 × 3 and a 1 × 1 convolution layer extracting shallow features. In order to better extract the high-frequency features of CT images and improve the image contrast, a multi-scale attention module is designed to adaptively detect the information of different scales, improve the expression ability of features, integrate the channel attention mechanism and spatial attention mechanism, and pay more attention to important information, retain more valuable information. Finally, sub-pixel convolution is used to improve the resolution of CT image and reconstruct high-resolution CT image. The experimental results show that this method can effectively improve the CT image contrast and suppress the noise. The peak signal-to-noise ratio and structural similarity of the reconstructed CT image are better than the comparison method, and has a good subjective visual effect.

4.
Chem Res Toxicol ; 35(12): 2271-2284, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36440846

RESUMO

Matrine (MT) is a major bioactive compound extracted from Sophorae tonkinensis. However, the clinical application of MT is relatively restricted due to its potentially toxic effects, especially hepatotoxicity. Although MT-induced liver injury has been reported, little is known about the underlying molecular mechanisms. In this study, transcriptomics and metabolomics were applied to investigate the hepatotoxicity of MT in mice. The results indicated that liver injury occurred when the administration of MT (30 or 60 mg/kg, i.g) lasted for 2 weeks, including dramatically increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. The metabolomic results revealed that steroid biosynthesis, purine metabolism, glutathione metabolism, and pyruvate metabolism were involved in the occurrence and development of MT-induced hepatotoxicity. Further, the transcriptomic data indicated that the downregulation of NSDHL with CYP51, FDFT1, and DHCR7, involved in steroid biosynthesis, resulted in a lower level of cholic acid. Besides, Gstps and Nat8f1 were related to the disorder of glutathione metabolism, and HMGCS1 could be treated as the marker gene of the development of MT-induced hepatotoxicity. In addition, other metabolites, such as taurine, flavin mononucleotide (FMN), and inosine monophosphate (IMP), also made a contribution to the boosting of MT-induced hepatotoxicity. In this work, our results provide clues for the mechanism investigation of MT-induced hepatotoxicity, and several biomarkers (metabolites and genes) closely related to the liver injury caused by MT are also provided. Meanwhile, new insights into the understanding of the development of MT-induced hepatotoxicity or other monomer-induced hepatotoxicity were also provided.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Camundongos , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Matrinas , Transcriptoma , Metabolômica/métodos , Fígado/metabolismo , Glutationa/metabolismo , Esteroides/metabolismo , 3-Hidroxiesteroide Desidrogenases/metabolismo
5.
Front Pharmacol ; 13: 794277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355711

RESUMO

Zanthoxylum nitidum (Roxb.) DC. (ZN), with strong effects of anti-inflammation and antioxidant activities is treated as a core herb in traditional Chinese medicine (TCM) preparation for treating stomachache, toothache, and rheumatoid arthritis. However, the active ingredients of ZN are not fully clarified due to its chemical complexity. In the present study, a double spectrum-effect analysis strategy was developed and applied to explore the bioactive components in herbs, and ZN was used as an example. Here, the chemical components in ZN were rapidly and comprehensively profiled based on the mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension approaches. Furthermore, the fingerprints of 20 batches of ZN samples were analyzed by high-performance liquid chromatography, and the anti-inflammatory and antioxidant activities of the 20 batches of ZN samples were studied. Finally, the partial least squares regression (PLSR), gray relational analysis models, and Spearman's rank correlation coefficient (SRCC) were applied to discover the bioactive compounds in ZN. As a result, a total of 48 compounds were identified or tentatively characterized in ZN, including 35 alkaloids, seven coumarins, three phenolic acids, two flavonoids, and one lignan. The results achieved by three prediction models indicated that peaks 4, 12, and 17 were the potential anti-inflammatory compounds in ZN, whereas peaks 3, 5, 7, 12, and 13 were involved in the antioxidant activity. Among them, peaks 4, 5, 7, and 12 were identified as nitidine, chelerythrine, hesperidin, and oxynitidine by comparison with the standards and other references. The data in the current study achieved by double spectrum-effect analysis strategy had great importance to improve the quality standardization of ZN, and the method might be an efficiency tool for the discovery of active components in a complex system, such as TCMs.

6.
J Stroke Cerebrovasc Dis ; 31(3): 106281, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35026495

RESUMO

OBJECTIVE: Hyperglycemia is often observed in the patients after acute stroke. This study aims to elucidate the potential effect and mechanism of hyperglycemia by screening microRNAs expression in intracerebral hemorrhage mice. METHODS: We employed the collagenase model of intracerebral hemorrhage. Twenty male C57BL/6 mice were used and randomly divided in normo- and hyperglycemic. The hyperglycemia was induced by intraperitoneally injection of 50% of Dextrose (8 mL/kg) 3 hours after intracerebral hemorrhage. The neurologic impairment was investigated by neurologic deficit scale. To study the specific mechanisms of hyperglycemia, microRNAs expression in perihematomal area was investigated by RNA sequencing. MicroRNAs expression in hyperglycemic intracerebral hemorrhage animals were compared normoglycemic mice. Functional annotation analysis was used to indicate potential pathological pathway, underlying observed effects. Finally, polymerase chain reaction validation was administered. RESULTS: Intraperitoneal injection of dextrose significantly increased blood glucose level. That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals. A total of 73 differentially expressed microRNAs were identified via transcriptomics analysis. Bioinformatics analyses showed that these microRNAs were significantly altered in several signaling pathways, of which the hedgehog signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute intracerebral hemorrhage. Furthermore, polymerase chain reaction results validated the correlation between microRNAs and hedgehog signaling pathway. CONCLUSIONS: MicroRNA elevated in hyperglycemia group may be involved in worsening the neurological function via inhibiting the hedgehog signaling, which provides a novel molecular physiological mechanism and lays the foundation for treatment of intracerebral hemorrhage.


Assuntos
Proteínas Hedgehog , MicroRNAs , Transdução de Sinais , Transcriptoma , Animais , Hemorragia Cerebral/genética , Modelos Animais de Doenças , Glucose/toxicidade , Proteínas Hedgehog/metabolismo , Hiperglicemia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma/genética
7.
Nat Prod Res ; 36(7): 1679-1685, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32815422

RESUMO

Five new phloroglucinol derivatives were isolated from Syzygium brachyantherum, and their structures were elucidated as brachyanones A-E (1-5) on the basis of the extensive spectroscopic analysis. Among them, compounds 1 and 3 exhibited significant inhibitory activity against α-glucosidase with IC50 of 2.57 and 0.97 µM, respectively. Furthermore, compound 4 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory effect with inhibition ratio of 89.42% at 100 µM. This discovery indicates that phloroglucinol derivatives with long aliphatic chain possibly play an important role in antidiabetic activity of Syzygium plants, and they could function as a promising antidiabetic agent.


Assuntos
Syzygium , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Estrutura Molecular , Floroglucinol/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Syzygium/química , alfa-Glucosidases/metabolismo
8.
Front Oncol ; 11: 654674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094944

RESUMO

BACKGROUND: Compared to open esophagectomy (OE), minimally invasive esophagectomy (MIE) is associated with lower morbidity and mortality. However, lymph node (LN) dissection around the recurrent laryngeal nerve (RLN) is still an important factor that affects the length of the learning curve of MIE. This study aims to evaluate the surgical outcomes of the first nearly 5-year period and explore the learning curve for LN dissection around the RLN in McKeown MIE by a new single surgical team. METHODS: A total of 285 consecutive patients who underwent McKeown MIE between March 2016 and September 2020 were included at our institution. According to the cumulative sum (CUSUM) analysis of LN dissection around the RLN, the patients were divided into three groups: exploration period, adjustment period, and stable period. We assessed the impact of surgical proficiency on postoperative outcomes and explored the learning curve for LN dissection around the RLN in McKeown MIE. RESULTS: The CUSUM graph showed that a point of upward inflection for LN dissection around the RLN was observed in 151 cases. After 151 cases, LNs around the right and left RLNs were dissected thoroughly compared to the exploration and adjustment period (P = 0.010 and P = 0.012, respectively), and the postoperative incidence of hoarseness significantly decreased from 11.1 to 1.5% (P<0.001). CONCLUSIONS: Our study results revealed that not only are the LN, around the RLN, sufficiently dissected but also the incidence of hoarseness significantly decreased in the stable phase. Consequently, the learning curve length was approximately 151 cases for LN dissection around the RLN in McKeown MIE.

9.
Front Cell Infect Microbiol ; 11: 640225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996624

RESUMO

Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis-associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in Alismatis rhizoma which is well known for dietary herb. Alismatis rhizoma is often used clinically to treat gastrointestinal diseases in China. In this study, we investigated the potential prevention of AB23A in male mouse models of azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC. AB23A intervention alleviated the body weight loss, disease activity index, colon tumor load, tissue injury, and inflammatory cytokine changes in CAC mice. AB23A intervention leads to remarkable reductions in the activation of TLR, NF-κB and MAPK. AB23A significantly decreased the phosphorylation of p38, ERK, and JNK and up-regulated mucin-2 and the expression of tight junction proteins. The gut microbiota of AB23A-interfered mice was characterized with high microbial diversity, the reduced expansion of pathogenic bacteria, such as Klebsiella, Citrobacter, and Akkermansia, and the increased growth of bacteria including Bacteroides, Lactobacillus, and Alloprevotella. These data reveal that AB23A has the potential to be used to treat CAC in the future.


Assuntos
Neoplasias Associadas a Colite , Colite , Microbioma Gastrointestinal , Animais , Azoximetano , China , Colestenonas , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sulfatos
10.
Oncol Lett ; 21(6): 429, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33868467

RESUMO

Lung cancer is the leading cause of cancer-associated death worldwide and exhibits a poor prognosis. The present study aimed to determine the effect of long non-coding (lnc)RNA-LINC00473 on the development of non-small cell lung cancer (NSCLC) cells by regulating the expression of microRNA (miR)-497-5p. Reverse transcription-quantitative PCR was conducted to detect the level of LINC00473 and miR-497-5p. An MTT assay, flow cytometry and Transwell tests were performed to evaluate the proliferation, apoptosis, migration and invasion of NSCLC cells. Western blotting was performed to detect the expression of apoptosis- and migration-related proteins. RNA immunoprecipitation and a luciferase reporter assay were performed to verify the regulatory relationship between lncRNA-LINC00473 and miR-497-5p. LINC00473 expression was upregulated in lung cancer tissues and NSCLC cells (A549 and H1299) when compared with adjacent tissues or human bronchial epithelial cell lines and the 5-year survival rate was lower in patients with high LINC00473 expression compared with in patients with low LINC00473 expression. A negative correlation between LINC00473 and miR-497-5p was observed in lung cancer tissues. Proliferation, migration and invasion as well as the related protein levels were increased in A549 and H1299 transfected with pcDNA3.1-LINC00473, while the opposite results were obtained in A549 and H1299 transfected with small interfering (si)-LINC00473. Notably, it was demonstrated that LINC00473 could bind directly with miR-497-5p and inhibit its expression. miR-497-5p inhibitors reversed the effect of si-LINC00473. Furthermore, the present study demonstrated that LINC00473 promoted the malignant behaviour of NSCLC cells via regulating the ERK/p38 and MAPK signalling pathways and the expression of miR-497-5p.

11.
Bioorg Med Chem Lett ; 30(17): 127407, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738992

RESUMO

In this study, seven 30-norlupane derivatives (2-8) wasobtained from the chemical oxidation ofbetulinic acidfollowed bybiotransformationviaBacillus megateriumCGMCC 1.1741. And metabolites 2-4 and 6-8 were newly identified products. In the first step, betulinic acid was chemically oxidizedto platanic acid (1). Following the chemical oxidation, B. megaterium catalyzed the hydroxylation at C-7, C-11, C-15 and C-23 of platanic acid (1) as well as the oxidation of C-3 hydroxyl group. Compared to the labor-intensive isolation from natural plants, this chemical-microbial semi-synthesis is more capable to provide increased structural diversity of oxygenated 30-norlupane. Finally, the potential neuroprotective effect of the derivatives was assessed on neuron-like PC12 cells induced by cobalt chloride (CoCl2). Metabolite 6 showed a potent neuroprotective activity.


Assuntos
Fármacos Neuroprotetores/química , Triterpenos Pentacíclicos/química , Animais , Bacillus megaterium/química , Bacillus megaterium/metabolismo , Biotransformação , Sobrevivência Celular/efeitos dos fármacos , Cobalto/toxicidade , Hidroxilação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxirredução , Células PC12 , Triterpenos Pentacíclicos/síntese química , Triterpenos Pentacíclicos/metabolismo , Triterpenos Pentacíclicos/farmacologia , Ratos , Ácido Betulínico
12.
Bioorg Med Chem Lett ; 30(4): 126947, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31924497

RESUMO

Tandem whole-cell biotransformation was applied successfully to deliver novel pentacyclic triterpenoid derivatives for the first time. In this process, the starting substrate oleanolic acid (1) was biotransformed into a hydroxylated metabolite 1a by Rhizopus chinensis CICC 40335 and then was further glycosylated to 1b by Bacillus subtilis ATCC 6633. Moreover, metabolite 1a was furtherly oxidized by Streptomyces griseus ATCC 13273 and generated two new derivatives as 1c and 1d. To validate the feasibility, tandem biotransformation of 18ß-glycyrrhetinic acid (2) by R. chinensis and B. subtilis was also conducted and offered a glycosylated derivative (2c). Finally, the neuroprotective effects of the derivatives were assessed on neural injury PC12 cell model induced by cobalt chloride.


Assuntos
Fármacos Neuroprotetores/metabolismo , Triterpenos/química , Animais , Bacillus subtilis/metabolismo , Cobalto/toxicidade , Glicosilação , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Ácido Glicirretínico/metabolismo , Conformação Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ácido Oleanólico/química , Ácido Oleanólico/metabolismo , Células PC12 , Ratos , Rhizopus/metabolismo , Streptomyces/metabolismo , Triterpenos/metabolismo , Triterpenos/farmacologia
13.
BMC Cancer ; 18(1): 1167, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477473

RESUMO

BACKGROUND: Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells. METHODS: We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines. RESULTS: Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p = 0.007), positive lymph node metastasis (p = 0.005) and disease grade (p = 0.003). CONCLUSIONS: Through its ability to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Canais de Cátion TRPM/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Fator 4 Semelhante a Kruppel , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Canais de Cátion TRPM/antagonistas & inibidores
14.
Fitoterapia ; 131: 141-145, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30315862

RESUMO

Five new phloroglucinol derivatives (1-5) together with one known analogue (6) were isolated from the leaves of Syzygium austroyunnanense which is an edible folk medicine used for the treatment of diabetes. The new structures were elucidated as austroyunones A - E (1-5) by means of the extensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR). Compounds 4-6 showed obvious protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. This discovery of new phloroglucinols and their bioactivities provided a scientific basis for the application of S. austroyunnanense as an edible and medicinal plant.


Assuntos
Floroglucinol/isolamento & purificação , Folhas de Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Syzygium/química , China , Estrutura Molecular , Floroglucinol/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
15.
Neural Regen Res ; 13(2): 347-352, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29557387

RESUMO

Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson's disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is considered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson's disease (four men and two women, aged 37-65 years), who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson's Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 µs and frequency at 130 Hz. Voltage adjustment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov (identifier: NCT01934881).

16.
Fitoterapia ; 125: 33-40, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29269236

RESUMO

To discover new potent cytotoxic steroidal saponins, a series of tigogenin neoglycosides were synthesized via oxyamine neoglycosylation for the first time. The preliminary bioassays for their in vitro antitumor activities against five human cancer cell lines (A375, A-549, HCT-116, HepG2 and MCF-7) were conducted. The results revealed a sugar-dependent activity profile of their cytotoxicity, the glycoconjugation converted the non-active tigogenin to the most potential product Tg29 ((3R)-N-methoxyamino-tigogenin-ß-2-deoxy-d-galactoside) with IC50 value of 2.7µM and 4.6µM against HepG2 and MCF-7 cells respectively. And the 3R-tigogenin neoglycosides exhibited enhanced antitumor activity while the 3S-tigogenin almost showed no activity. Among the five cell lines, HepG2 and MCF-7 cells showed more sensitive cytotoxic responses to the products. Therefore, the neoglycosylation could be a promising strategy for the synthesis of antitumor steroidal saponins and it also proved the essential role of carbohydrate moiety of steroidal saponins in the biological activity.


Assuntos
Saponinas/síntese química , Espirostanos/síntese química , Espirostanos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Saponinas/farmacologia
17.
Appl Biochem Biotechnol ; 183(3): 1026-1034, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28455804

RESUMO

Colchicinoids and their derivatives are of great importance in pharmaceutical applications, and colchicine is usually used as the first choice for the treatment of gout. To expand the structural diversities and clinical application of colchicinoids, many attempts have been established for the derivatives with better activity or less toxicity. Herein, in this paper, we report a direct microbial transformation of colchicine into 2-O-demethyl-colchicine (M1) and 3-O-demethl-colchicine (M2) by Streptomyces griseus ATCC 13273. It is noteworthy that when DMF was used as co-solvent, the yield of M1 and M2 could reach up to 51 and 31%, respectively. All the structures of the metabolites were elucidated unambiguously by ESI-MS, 1H-NMR, 13C-NMR, and 2D-NMR spectroscopy.


Assuntos
Biocatálise , Colchicina/química , Colchicina/metabolismo , Poluentes Ambientais/química , Poluentes Ambientais/metabolismo , Streptomyces griseus/metabolismo , Biotransformação , Metilação , Estereoisomerismo , Especificidade por Substrato
18.
Bioorg Med Chem Lett ; 27(11): 2575-2578, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28427811

RESUMO

Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1ß,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1ß-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1ß,3ß, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1ß,11α-dihydroxy-3-oxo-urs-12-en-28-O-ß-d-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) - stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC50 values of 1.243 and 1.711µM, respectively. A primary structure-activity relationship was also discussed.


Assuntos
Bacillus megaterium/metabolismo , Triterpenos/metabolismo , Animais , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia , Ácido Ursólico
19.
Bioorg Med Chem Lett ; 27(4): 1026-1030, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28109788

RESUMO

To discover new inhibitors on tissue factor procoagulant activity, 20 pentacyclic triterpenes were semi-synthetized through microbial transformation and assayed on the model of human THP-1 cells stimulated by lipopolysaccharide. In the biotransformation two types of reactions were observed, regio-selective hydroxylation and glycosylation. The bioassay results showed that most of tested compounds were significant effective on this model and two of the biotransformation products 23-hydroxy-28-O-ß-d-glucopyranosyl betulinic acid (3d) and 28-O-ß-d-glucopyranosyl oleanic acid (1a) exhibited most potential activities with the IC50 values of 0.028, 0.035nM respectively. The preliminary structure and activity relationship analysis revealed that the aglycones with single free hydroxyl group on the skeleton (1, 1j) were less effective than that with more free hydroxyl groups (1d, 1f, 2), mono-glycosylation can significantly enhance their inhibitory effects. Our findings also provide some potential leading compounds for tissue factor-related diseases, such as cancer and cardiovascular diseases.


Assuntos
Tromboplastina/antagonistas & inibidores , Triterpenos/farmacologia , Glicosilação , Humanos , Hidroxilação , Relação Estrutura-Atividade , Triterpenos/química
20.
Chin J Nat Med ; 13(10): 796-800, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26481382

RESUMO

The present study was designed to explore the substrate scope and biocatalytic capability of Gliocladium deliquescens NRRL 1086 on phenolic natural products. Emodin was subjected to the fermentation culture of Gliocladium deliquescens NRRL 1086 according to the standard two-stage protocol. The biotransformation process was monitored by HPLC-DAD-MS, the main product was isolated by column chromatography, and the structure was elucidated on the basis of NMR spectroscopy. Emodin could be fully metabolized by Gliocladium deliquescens NRRL 1086, resulting in high yield of emodin 6-O-ß-D-glucopyranoside and small amount of sulfated product. In conclusion, our results may provide a convenient method to prepare emodin 6-O-ß-D-glucopyranoside and the microbe catalyzed glucosylation/sulfation will give an inspiration to pharmacokinetic model studies in vitro.


Assuntos
Emodina/metabolismo , Fermentação , Gliocladium/metabolismo , Glucosídeos/metabolismo , Extratos Vegetais/metabolismo , Reatores Biológicos , Biotransformação , Glicosilação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Fenóis/metabolismo
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