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1.
Chemistry ; 29(59): e202302217, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37552566

RESUMO

Since the discovery of urea inclusion compounds (UICs) in 1940, the handedness of this chiral helical system has not been established experimentally. Here three UIC systems containing only light atoms were studied. The optical rotations were first measured, and the absolute structures of the enantiomorphic domains of three UICs were determined by single crystal X-ray diffraction (SCXRD). The correlation between the optical rotation and the absolute configuration of the UICs was finally established, showcasing the power of absolute structure determination by SCXRD, which is essential in structural chemistry and pharmaceutical research.

2.
Chemistry ; 29(59): e202303140, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37794612

RESUMO

Invited for the cover of this issue is the group of Bo Wang at Biogen. The image depicts the sectored chiral domains of urea inclusion compounds. Read the full text of the article at 10.1002/chem.202302217.

3.
Emerg Infect Dis ; 27(9): 2379-2388, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34424183

RESUMO

Vertical transmission of group B Streptococcus (GBS) is among the leading causes of neonatal illness and death. Colonization with GBS usually is screened weeks before delivery during pregnancy, on the basis of which preventive measures, such as antibiotic prophylaxis, were taken. However, the accuracy of such an antenatal screening strategy has been questionable because of the intermittent nature of GBS carriage. We developed a simple-to-use, rapid, CRISPR-based assay for GBS detection. We conducted studies in a prospective cohort of 412 pregnant women and a retrospective validation cohort to evaluate its diagnostic performance. We demonstrated that CRISPR-GBS is highly sensitive and offered shorter turnaround times and lower instrument demands than PCR-based assays. This novel GBS test exhibited an overall improved diagnostic performance over culture and PCR-based assays and represents a novel diagnostic for potential rapid, point-of-care GBS screening.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética
4.
Int J Mol Sci ; 18(1)2017 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-28085116

RESUMO

Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes (P. acnes) and Staphylococcus aureus, and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P. acnes-induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin (1), punicalin (2), strictinin A (3), and granatin B (4), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1, 3, and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E2 production in heat-killed P. acnes-treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin (1), the most effective component in PG-E, can be employed as a quality control marker.


Assuntos
Acne Vulgar/prevenção & controle , Edema/prevenção & controle , Lythraceae/química , Extratos Vegetais/farmacologia , Acne Vulgar/microbiologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Orelha/patologia , Edema/microbiologia , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Lipase/antagonistas & inibidores , Lipase/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Microscopia Eletrônica de Varredura , Estrutura Molecular , Extratos Vegetais/química , Propionibacterium acnes/efeitos dos fármacos , Propionibacterium acnes/crescimento & desenvolvimento , Propionibacterium acnes/fisiologia , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/ultraestrutura , Taninos/química , Taninos/farmacologia
5.
Saudi Pharm J ; 25(4): 620-624, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579901

RESUMO

Acitretin has been a valuable option for the treatment of psoriasis, however, the molecular events of acitretin leading to the normalization of keratinocytes differentiation on psoriasis patients have not been fully explored. To investigate whether there were certain relationship between keratinocytes proliferation and JAK/STAT signaling pathways in psoriasis, and how acitretin modulated the signaling pathways. HaCaT cells, an in vitro immortal human keratinocyte cell line, was chosen as a in vitro model of psoriasis. The small interfering RNA targeting STAT1 (siRNA-STAT1) and STAT3 (siRNA-STAT3) were subsequently transfected into the HaCaT cells which were treated with or without acitretin. We found that HaCaT cells proliferation and the expression of STAT1 or STAT3 were inhibited by acitretin, siRNA-STAT1 and siRNA-STAT3. Our experimental data shows that acitretin might inhibit HaCaT cells proliferation in psoriasis by decreasing the expression of STAT- and STAT3-dependent mechanism.

6.
Zhonghua Yi Xue Za Zhi ; 93(42): 3343-6, 2013 Nov 12.
Artigo em Zh | MEDLINE | ID: mdl-24418028

RESUMO

OBJECTIVE: To explore the video-urodynamic characteristics and management in complete cervical and thoracic spinal cord injury patients. METHODS: Video-urodynamic examination was performed in 113 patients with complete cervical and thoracic spinal cord injury from January 2008 to May 2010. And their characteristics, managements and 3-year follow-up outcomes were reviewed and analyzed retrospectively. RESULTS: Among them, there were detrusor overactivity (n = 82, 72.57%), detrusor areflexia (n = 31, 27.43%), detrusor external sphincter dyssynergia (n = 71, 62.83%), low-compliance (n = 59, 52.21%), reflux (n = 6, 5.31%) and ultrasonic uronephrosis (n = 12, 10.62%). According to the result of the video-urodynamic examination, detrusor overactivity patients chose oral anticholinergic agents, botulinum toxin type A injection method, detrusor areflexia patients chose regular intermittent catheterization for bladder training. During a 3-year follow-up, there were cystic calculus (n = 2) and urinary infection (n = 7).No special complication occurred. CONCLUSIONS: The video-urodynamic characteristics vary in complete cervical and thoracic spinal cord injury patients. The major symptoms include detrusor overactivity, detrusor external sphincter dyssynergia and low-compliance bladder. Proper management is essential for protecting upper urinary tract and preventing urinary system complication.


Assuntos
Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Urodinâmica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Estudos Retrospectivos , Traumatismos da Medula Espinal/complicações , Tórax , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Adulto Jovem
7.
Front Oncol ; 13: 1132177, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519780

RESUMO

Background: Statin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC. Materials and Methods: Cohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed. Results: Seventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I2 = 38%). Besides, for the outcome of OS and PFS, subgroup analyses showed similar results in patients with surgical and non-surgical anticancer treatments, and in patients with stage I-III and stage IV RCC (p values for subgroup difference all > 0.05). Conclusions: Statin use may be associated with improved survival outcomes in patients with RCC. Although prospective clinical studies should be considered to validate these results, these findings suggest that statins may be potential adjuvant therapy for patients with RCC.

8.
Chem Biodivers ; 9(1): 131-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22253110

RESUMO

A series of six isopimarane-type diterpene glycosides, along with an eremophilane-type sesquiterpene, i.e., elaeicolasides A-C (1-3, resp.), 16-(α-D-mannopyranosyloxy)isopimar-7-en-19-oic acid (4), hymatoxin K (5), hymatoxin L (6), and elaeicolalactone (7), were isolated from the AcOEt extract of the fermented broth of Stilbohypoxylon elaeicola YMJ173. Among these, 1-3 and 7 are new compounds based on their spectroscopic data and sugar composition analysis. The effects of 1-7 on the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells were evaluated. All these compounds inhibited NO production, detected as nitrite in the culture medium, in activated macrophages without any cytotoxicity at a concentration of 100 µM. Among these compounds, 2 showed a significant activity with the average maximum inhibition (E(max)) and median inhibitory concentration (IC(50)) values of 93.3±0.5% and 79.3±0.4 µM, respectively.


Assuntos
Macrófagos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Terpenos/química , Terpenos/farmacologia , Xylariales/metabolismo , Animais , Linhagem Celular , Fermentação , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Terpenos/isolamento & purificação , Xylariales/crescimento & desenvolvimento
9.
Front Physiol ; 13: 861895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615674

RESUMO

Objective: This study aimed to investigate the application value of the renal region of interest (ROI) corrected by computed tomography (CT) in single-kidney glomerular filtration rate (GFR) in patients with hydronephrosis. Methods: A total of 46 patients with hydronephrosis were divided into four groups based on their degree of unilateral hydronephrosis: a normal group (left kidney and right kidney) and three abnormal groups (mild, moderate, and severe hydronephrosis). GFR was measured using the two-sample method (tGFR). The single-kidney GFR of each patient was derived from differential renal function values in dynamic renal imaging multiplied by GFR. The single-kidney GFRs, including GFR from the Gates method (gGFRsingle) and CT area-corrected GFR (aGFRsingle), were compared with tGFRsingle. A paired-sample t-test and Pearson's test were used for data analysis. p < 0.05 was considered statistically significant. Results: There were no significant differences between aGFRsingle and tGFRsingle in patients in the normal, mild hydronephrosis, and moderate hydronephrosis groups (t = -0.604∼1.982, all p > 0.05), but there was a significant difference between them in the severe hydronephrosis group (t = 2.302, p < 0.05). There were no significant differences between gGFRsingle and tGFRsingle in the normal and mild hydronephrosis groups (t = 0.194∼0.962, all p > 0.05), but there was a significant difference between them in the moderate and severe hydronephrosis groups (t = 3.321, 3.494, p < 0.05). Both gGFRsingle and aGFRsingle were correlated with tGFRsingle, with aGFRsingle being more strongly correlated (r = 0.890, p < 0.001). Conclusion: In patients with moderate hydronephrosis, aGFRsingle is more strongly correlated with tGFRsingle than gGFRsingle. However, in patients with severe hydronephrosis and accompanying renal morphological changes, the aGFRsingle measured by the renal ROI area-correction method using CT has higher accuracy and better clinical application value than the conventional gGFRsingle.

10.
Artigo em Inglês | MEDLINE | ID: mdl-21799672

RESUMO

The rhizome of Atractylodes ovata De Candolle is rich in essential oils, which are usually removed by processing. In this study, anti-oxidative abilities of essential oils and aqueous extracts of A. ovata rhizome were explored, and the influence of processing on the anti-oxidative abilities was examined. Essential oils and aqueous extracts of A. ovata were extracted by boiling water and steam distillation, respectively. Quality of these two A. ovata samples was controlled by HPLC and GC-MS system, and anti-oxidative abilities were then evaluated. Results showed that surface color of A. ovata turned to brown and chemical components were changed by processing. Contents of both atractylon and atractylenolide II decreased in the essential oils, but only the contents of atractylon decreased by processing. Atractylenolide III increased in both A. ovata samples. However, A. ovata essential oils displayed stronger anti-oxidative abilities than aqueous extracts in DPPH-scavenging, TBH-induced lipid peroxidation and catalase activity assays. Moreover, the bioactivity of essential oils from raw A. ovata was stronger than oils from processed A. ovata. On the other hand, cytotoxicity of A. ovata essential oils was stronger than that of aqueous extracts, and was more sensitive on H9C2 cell than NIH-3T3 and WI-38 cells. In contrast, stir-frying processing method increased cytotoxicity of essential oils, but the cytotoxicity was ameliorated when processed with assistant substances. The results suggested that phytochemical components and bioactivity of A. ovata were changed after processing and the essential oils from raw A. ovata showed better anti-oxidative and fewer cytotoxicity effects.

11.
Chem Biodivers ; 8(12): 2285-90, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22162166

RESUMO

One new betaenone, theissenoic acid (1), together with three new acetogenins, theissenolactones A-C (2-4, resp.), were isolated from the fermented broth of Theissenia cinerea 89091602 isolated in Taiwan. The structures of 1-4 were elucidated by spectroscopic methods. Biological tests revealed that 3 and 4 exhibited moderate growth-inhibitory activities against A549 lung cancer cell line with GI(50) values of 14.9 and 47.9 µM, respectively.


Assuntos
Acetogeninas/química , Acetogeninas/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Xylariales/química , Acetogeninas/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Xylariales/crescimento & desenvolvimento
12.
Molecules ; 16(11): 9451-66, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-22075574

RESUMO

A new biflavonol glycoside, quercetin-3-O-ß-D-glucopyranoside-(3'→O-3''')-quercetin-3-O-ß-D-galactopyranoside (9), together with eight known compounds was isolated for the first time from the leaves of Machilus zuihoensis Hayata (Lauraceae). The structure of compound 9 was elucidated by various types of spectroscopic data analysis. Analysis of the biological activity assay found that compound 9 showed significant superoxide anion scavenging activity (IC50 is 30.4 µM) and markedly suppressed LPS-induced high mobility group box 1 (HMGB-1) protein secretion in RAW264.7 cells. In addition, the HMGB-1 protein secretion was also inhibited by quercitrin (3), ethyl caffeate (6), and ethyl 3-O-caffeoylquinate (7) treatment. In the LPS-stimulated inducible nitric oxide synthase (iNOS) activation analysis, two known compounds, quercetin (1) and ethyl caffeate (6), were found to markedly suppress nitric oxide (NO) production (IC50 value, 27.6 and 42.9 µM, respectively) in RAW264.7 cells. Additionally, it was determined that ethyl caffeate (6) down-regulated mRNA expressions of iNOS, IL-1ß, and IL-10 in the LPS-treatment of RAW264.7 cells via a suppressed NF-kB pathway. These results suggested for the first time that the new compound 9 and other constituents isolated from M. zuihoensis have potential anti-inflammatory and superoxide anion scavenging effects. These constituents may be useful for treating various inflammatory diseases.


Assuntos
Anti-Inflamatórios , Sequestradores de Radicais Livres , Lauraceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/farmacologia , Linhagem Celular , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Galactosídeos/química , Proteína HMGB1/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Monossacarídeos/química , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacologia , Superóxidos/química , Fator de Necrose Tumoral alfa/metabolismo
13.
Lab Chip ; 21(15): 2881-2891, 2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34219135

RESUMO

Precise isolation and analysis of circulating tumor cells (CTCs) from blood samples offer considerable potential for cancer research and personalized treatment. Currently, available CTC isolation approaches remain challenging in the quest for simple strategies to achieve cell isolation with both high separation efficiency and high purity, which limits the use of captured CTCs for downstream analyses. Here, we present a filter deterministic lateral displacement concept to achieve one-step and label-free CTC isolation with high throughput. Unlike conventional deterministic lateral displacement (DLD) devices, the proposed method uses a hydrodynamic cell sorting design by incorporating a filtration concept into a DLD structure, and enables high-throughput and clog-free isolation by a cascaded microfluidic design. The cascaded filter-DLD (CFD) design demonstrated enhanced performance for size-based cell separation, and achieved high separation efficiency (>96%), high cell purity (WBC removal rate 99.995%), high cell viability (>98%) and high processing rate (1 mL min-1). Samples from lung cancer patients were analyzed using the CFD-Chip, CTCs and tumor cell-leukocyte fusion cells were efficiently collected, and changes in CTC levels were used for treatment response monitoring. The CFD-Chip platform isolated CTCs with good viability, enabling direct downstream analysis with single-cell RNA sequencing. Transcriptome analysis of enriched CTCs identified new subtypes of CTCs such as tumor cell-leukocyte fusion cells, providing insights into cancer diagnostics and therapeutics.


Assuntos
Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Contagem de Células , Linhagem Celular Tumoral , Separação Celular , Humanos , Microfluídica
14.
Zhonghua Wai Ke Za Zhi ; 48(23): 1774-7, 2010 Dec 01.
Artigo em Zh | MEDLINE | ID: mdl-21211381

RESUMO

OBJECTIVE: To evaluate clinical efficacy of holmium laser enucleation of the prostate in the treatment of benign prostatic hyperplasia (BPH) and overactive bladder (OAB). METHODS: From May 2007 to May 2010, a total of 37 patients diagnosed BPH and OAB were treated by holmium laser enucleation of the prostate. After a mean follow-up of 4.9 months postoperatively, indices such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), residual urine volume and video urodynamics were monitored and statistically analyzed. RESULTS: The mean preoperative IPSS and QOL score were 29.6 ± 5.2 and 4.3 ± 0.9, and decreased to 4.6 ± 1.2 and 1.2 ± 1.0 postoperative. The mean Qmax was (6 ± 3) ml/s preoperative and increased to (21 ± 5) ml/s postoperative. Preoperative average residual urine volume was (167 ± 11) ml, decreased to (41 ± 18) ml after operation. During follow-up, 86.5% patients' symptoms and quality of life improved continuously, however 13.5% patients existed residual postoperative OAB symptoms. CONCLUSIONS: When BPH with OAB patients exist bladder outlet obstruction, bladder outlet obstruction should be relieved first then OAB symptoms can be relieved in majority of patients, but some patients have residual symptoms.


Assuntos
Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Bexiga Urinária Hiperativa/complicações , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Lasers de Estado Sólido/uso terapêutico , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Resultado do Tratamento , Bexiga Urinária Hiperativa/cirurgia
15.
Zhonghua Wai Ke Za Zhi ; 47(2): 128-31, 2009 Jan 15.
Artigo em Zh | MEDLINE | ID: mdl-19563009

RESUMO

OBJECTIVE: To explore the efficacy of neuromodulation (including sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation) for the treatment to neurogenic bowel dysfunction due to spinal cord injury. METHODS: From January 2006 to April 2008, 9 patients with neurogenic constipation after spinal cord injury underwent the therapy of neuromodulation, 1 patient underwent the therapy of sacral neuromodulation, 8 patients underwent the therapy of dorsal penile/clitoral nerve neuromodulation. The therapeutic efficacy was evaluated and followed up by means of Wexner constipation score. RESULTS: One patient received permanent electrode and neurostimulator implantation and constipation were improved continuously. A significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (preoperative baseline: median 22; after implantation: median 9). Four patients were effective after the therapy of dorsal penile/clitoral nerve neuromodulation. Wexner constipation score decrease from 19 to 11 after 12 weeks dorsal penile/clitoral nerve neuromodulation. Patients also showed a significant improvement in their symptoms and quality of life during follow up. CONCLUSIONS: Sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation may be effective for some neurogenic constipation. However there are no methods successfully identify the candidate who will be beneficial before the procedure. Good quality research data are needed to evaluate the effects of sacral neuromodulation and dorsal penile/clitoral nerve neuromodulation for these conditions.


Assuntos
Constipação Intestinal/terapia , Terapia por Estimulação Elétrica/métodos , Traumatismos da Coluna Vertebral/complicações , Constipação Intestinal/etiologia , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento
16.
Toxicol Lett ; 313: 108-119, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251971

RESUMO

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs) and are associated with the progression of many cancers, including liver cancer. The present study investigated the effect of 2,3'4,4',5-pentachlorobiphenyl (PCB118) on hepatocellular carcinoma cell proliferation and its underlying mechanisms. The results indicated that PCB118 exposure promotes the proliferation and glycolysis of hepatocellular carcinoma SMMC-7721 cells. Moreover, PCB118 exposure increased the expression level of pyruvate kinase M2 (PKM2) and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the induction of cell proliferation and glycolysis by PCB118. PCB118 stimulated reactive oxygen species (ROS) production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Treatment with the antioxidants N-acetyl-L-cysteine (NAC) and superoxide dismutase (SOD) prevented PCB118-induced effects on PKM2, cell proliferation and glycolysis. Furthermore, we found that PCB118 activated NADPH oxidase through the aryl hydrocarbon receptor (AhR) in SMMC-7721 cells. Consistently, treatment with AhR shRNA suppressed PCB118-induced effects on PKM2, cell proliferation and glycolysis. Overall, these results indicated that PCB118 promotes HCC cell proliferation via PKM2-dependent upregulation of glycolysis, which is mediated by AhR/NADPH oxidase-induced ROS production.


Assuntos
Carcinógenos Ambientais/toxicidade , Carcinoma Hepatocelular/enzimologia , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/enzimologia , Proteínas de Membrana/metabolismo , Bifenilos Policlorados/toxicidade , Hormônios Tireóideos/metabolismo , Transporte Ativo do Núcleo Celular , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hormônios Tireóideos/genética , Proteínas de Ligação a Hormônio da Tireoide
17.
Zhonghua Wai Ke Za Zhi ; 46(20): 1525-8, 2008 Oct 15.
Artigo em Zh | MEDLINE | ID: mdl-19094643

RESUMO

OBJECTIVE: To explore the Video-urodynamic characteristics of various neurogenic bladder. METHODS: A total of 1800 patients with neurogenic bladder were included in our study from December 2002 to June 2008. All patients underwent Video-urodynamic studies. Urodynamic data was collected and analyzed. RESULTS: Urodynamic study showed detrusor overactivity in 71%, of which 60% with uninhibited sphincter relaxation, and acontractile detrusor in 29% stroke patients. No upper urinary tract deterioration was found in all 42 stroke patients. Detrusor overactivity without sphincter dyssynergia was found in 70% patients with head trauma. Seven patients with Parkinson disease showed detrusor overactivity, of which 3 with delayed sphincter relaxation. Detrusor overactivity was found in 91% and detrusor sphincter dyssynergia in 83% supra-sacral spinal cord injured patients. Acontractile detrusor was found in 73% patients with conus medullaris and cauda equina injury. Overall, upper urinary tract changes were found in 12% and vesicoureteral reflux in 4% spinal cord injured patients. Urodynamic study showed acontractile detrusor in 81%, reduced compliance in 86%, upper urinary tract changes in 55% and vesicoureteral reflux in 33% patients with myelodysplasia. Most patients (92%) with protruded lumbar disc showed detrusor areflexia. Normal bladder compliance was found in 88% patients with protruded lumbar disc. Urodynamic study showed reduced bladder sensation in 81% and detrusor under-activity in 76% patients with diabetic urinary bladder disease. CONCLUSIONS: Video-urodynamic study can provide the most detailed information about the bladder dysfunction. It is the most valuable examination before treatment of patients with neurogenic bladder.


Assuntos
Bexiga Urinaria Neurogênica/fisiopatologia , Urodinâmica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/etiologia
18.
Oncol Lett ; 16(6): 6998-7007, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30546433

RESUMO

This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial. In addition, a preliminary evaluation of the safety of NY-ESO-1 TCR-T cell therapy was performed in four patients with non-small cell lung cancer (NSCLC) enrolled in a clinical trial. It was well-tolerated and did not observe any serious adverse events post-infusion. Fever, anemia, and a decrease in white blood cell count were common adverse events, which were likely due to the TCR-T cell therapy. Two patients had clinical responses to NY-ESO-1 TCR-T cell therapy, including the 44-year-old female patient with LADC, who achieved a short-term partial response for 4 months, improved in Karnofsky performance status, and had a recovery of drug sensitivity. This suggests that TCR-T cell therapy targeting NY-ESO-1 antigen may be beneficial for HLA-A2-positive late-stage patients with NY-ESO-1-expressing NSCLC.

19.
J Investig Med ; 65(2): 376-381, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28130440

RESUMO

Psoriasis is an autoimmune disease, which is characterized by aberrantly high levels of inflammation, but the underlying pathogenic mechanisms are still not fully understood. Signal transducer and activator of transcription 1 (STAT1) and STAT3, and the downstream proteins suppressor of cytokine signaling 1 (SOCS1) and SOCS3, have been implicated in psoriasis disease progression. Calcipotriol, a synthetic derivative of vitamin D, has been used clinically to treat psoriasis, but the mechanism of action that underlies the beneficial effects of calcipotriol is still being explored. The objective of this study was to determine whether STAT1 and STAT3 signaling is involved in calcipotriol treatment. Using an in vitro immortal human keratinocyte cell line, HaCaT cells, as a psoriasis model, we examined the molecular signaling induced by calcipotriol treatment. We found that calcipotriol treatment or silencing of either STAT1 or STAT3 inhibited proliferation of HaCaT cells. Calcipotriol downregulated the expression of STAT1 and STAT3 at the messenger RNA (mRNA) and protein levels. The levels of phosphorylated STAT1 and STAT3 were also decreased, suggesting calcipotriol treatment inhibited STAT1 and STAT3 activation. Calcipotriol-mediated STAT inhibition was further substantiated by the downregulation of SOCS1 and SOCS3 at the mRNA and protein expression levels. Taken together, our results suggest a novel molecular mechanism for calcipotriol-mediated treatment effects in psoriasis.


Assuntos
Calcitriol/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Queratinócitos/citologia , Queratinócitos/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calcitriol/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
20.
Nucl Med Commun ; 37(5): 519-24, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26867167

RESUMO

OBJECTIVE: The aim of this study was to evaluate the difference in measured glomerular filtration rate (GFR) of an ectopic pelvic kidney between anterior and posterior image processing using Gates' method of renal dynamic imaging. METHODS: A total of 10 patients were studied retrospectively, with a single ectopic kidney in the pelvic cavity and a contralateral kidney at its normal anatomical position confirmed by ultrasound, computed tomography, renal dynamic imaging, etc. All images of ectopic kidneys were processed, and GFRs were measured using anterior and posterior Gates' method of renal dynamic imaging, respectively. The contralateral normal kidney was only processed on posterior imaging. The total GFRant of one patient, which was equal to the sum of the GFR of a normal kidney on posterior imaging and the GFR of an ectopic kidney on anterior imaging, was compared with the total GFRpost of two kidneys on posterior imaging, with the GFRtwo-sample from the two-sample method, and with the estimated GFR in the Chronic Kidney Disease Epidemiology Collaboration equation. All correlation analyses were carried out between GFRs obtained from three methods, and all patients were followed up. For statistical analysis, nonparametric rank tests were used, Bland-Altman graphs were plotted. RESULTS: The mean GFR of the ectopic kidney on anterior imaging was 27.48±12.24 ml/min/1.73 m. It was higher than the GFR (10.71±4.74 ml/min/1.73 m) on posterior imaging (t=-2.803, P<0.05). There were statistical differences between the total GFRant and the total GFRtwo-sample (Z=-2.295, P<0.05), between the total GFRant and the total GFRpost (Z=2.599, P<0.01), between the total GFRtwo-sample and the total GFRpost (Z=-2.191, P<0.05), and between the total GFRant and the estimated glomerular filtration rate (Z=-2.803, P<0.01). The bias of the total GFRant was different from that of the total GFRpost (Z=-2.191, P<0.05). There were no differences in the precision and accuracy within 30% of the total GFRant and that of the total GFRpost (precision: F=0.351, P>0.05), but there were statistical differences in the accuracy within 10% of the total GFRant and that of the total GFRpost (P<0.05). CONCLUSION: The GFR measured using Gates' method of anterior image processing was more accurate than the GFR obtained on posterior image processing in reflecting the function of an ectopic pelvic kidney in renal dynamic imaging.


Assuntos
Taxa de Filtração Glomerular , Processamento de Imagem Assistida por Computador/métodos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Anormalidades Urogenitais/diagnóstico por imagem , Anormalidades Urogenitais/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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