RESUMO
In an attempt to arrive at a more potent antitumor agent than the parent natural saponin hederacolchiside A1, 23 hederacolchiside A1 derivatives (4a-4w) were synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and screened in vitro for cytotoxicity against six human cancer cell lines. The structure-activity relationship of these compounds was elucidated, and the biological screening results showed that most of the compounds exhibited moderate to high levels of antitumor activities against the tested cell lines and some of them displayed more potent inhibitory activities compared with hederacolchiside A1. Compound 4f showed a 2- to 7-fold more potent activity than hederacolchiside A1. The mechanistic study of 4f revealed that this compound can induce cell apoptosis in HepG2 cells via mitochondrial-mediated intrinsic pathways.
Assuntos
Antineoplásicos/farmacologia , Saponinas/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Saponinas/síntese química , Saponinas/química , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
OBJECTIVE: To evaluate the effects of electromyography on the clinical manifestations and prognosis after posterior lumbar interbody fusion(PLIF) of degenerative lumbar diseases. METHODS: A retrospective analysis was performed on 68 patients with degenerative lumbar diseases, including 29 males and 39 females, aged 21 to 84 years old, who underwent electromyogram (EMG) from January 2018 to October 2019. The patients were divided into negative and positive groups according to whether theresults of EMG was normal or abnormal, PLIF surgery was performed in both groups. The preoperative duration of illness, postoperative recovery time, operative time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) of low back and lower limb, the Japanese Orthopedic Association(JOA) score before and after operation. RESULTS: All patients were follow-up from 26 to 39 months. The subjective symptoms, clinical signs, daily activities and JOA total scores after operation in two groups were significantly higher than those before preoperation(P<0.05);the clinical signs score and total JOA score in the negative group at 3 months after operation were higher than those in the positive group(P<0.05). The VAS score of leg pain in the negative group after 1 and 3 months was less than that in the positive group(P<0.05). Patients 's illness time, postoperative recovery time, hospitalization time and implantation time in the negative group were shorter than those in the positive group(P<0.05). At other time points, there was no significant difference in low pain VAS, leg pain VAS, JOA scores in the two groups(P>0.05). There was no significant difference in the operation time and intraoperative bleeding volume between the two groups(P>0.05). CONCLUSION: Patients with normal electromyography had shorter disease duration than ones with abnormal electromyography in lumbar degenerative disease;after PLIF, patients with normal electromyography recovered faster than ones with abnormal electromyography, but the results of electromyography had no effect on the final prognosis of PLIF surgery.
Assuntos
Fusão Vertebral , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Resultado do Tratamento , DorRESUMO
BACKGROUND: The present study was carried out to determine whether a quantitative relationship exists between the expressions of 3 cancer stem cell (CSC) markers and the degree of differentiation of gastric cancer. METHODS: The expressions of 3 putative CSC markers, ABCB1, ABCG2, and CD133, were detected in 90 human gastric adenocarcinoma cases by immunofluorescence assay. The differentiation statuses of 3 gastric cancer cell lines (the undifferentiated gastric cancer cell line HGC-27, the poorly differentiated gastric cancer cell line BGC-823, and the moderately-poorly differentiated gastric adenocarcinoma cell line SGC-7901) were observed and compared by performing the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Gastric xenotransplant cancers in nude mice were constructed to compare the malignancy of the 3 variously differentiated gastric cancer cell lines. The expressions of the 3 putative CSC markers were also detected in the 3 gastric cancer cell lines in vitro by flow cytometric analysis and in the 3 gastric xenotransplant cancers in vivo by immunofluorescence staining. RESULTS: The expressions of ABCB1, ABCG2, and CD133 were generally correlated with the degree of differentiation of the gastric cancers. In the human gastric adenocarcinomas and in the cancer cell lines, the expressions of ABCB1, ABCG2, and CD133 increased with the increases in the malignancy grades of the gastric cancers. In the human gastric adenocarcinomas, poorly differentiated adenocarcinoma expressed more ABCB1, ABCG2, and CD133 than well-differentiated adenocarcinoma. In addition, the expressions of ABCB1 and CD133 were higher in the diffuse type than in the intestinal type of human gastric cancers. The undifferentiated cell line HGC-27 expressed more putative CSC markers than the moderately-poorly differentiated cell line SGC-7901. Similar results were observed in the xenotransplant tumors that arose from the 3 gastric cancer cell lines. CONCLUSIONS: The expressions of the CSC markers ABCB1, ABCG2, and CD133 differed in the gastric cancers with various degrees of differentiation, with poorly differentiated gastric cancer expressing relatively more CSC markers.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adenocarcinoma/patologia , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Glicoproteínas/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Peptídeos/metabolismo , Neoplasias Gástricas/patologia , Antígeno AC133 , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adenocarcinoma/metabolismo , Adulto , Idoso , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of oleanolic acid derivatives bearing acetyl-substituted l-arabinose moiety has been synthesized and screened in vitro for cytotoxicity against ten cancer cell lines and four normal cell lines. The antiproliferative evaluation indicated that synthetic derivatives showed excellent selectivity, as they were toxic against only A431 cell line. Among them, the compound 6 possesses the best inhibitory activity. A series of pharmacology experiments showed that compound 6 significantly induced A431 cells apoptosis and cell cycle arrest, which could serve as a promising lead candidate for further study.
Assuntos
Antineoplásicos/farmacologia , Arabinose/farmacologia , Ácido Oleanólico/farmacologia , Saponinas/farmacologia , Acetilação , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Arabinose/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Conformação Molecular , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Saponinas/síntese química , Saponinas/químicaRESUMO
BACKGROUND AND AIM: This study investigated whether 19-peptide, a fragment of tumstatin, inhibited the growth of gastric tumor cells in vitro and in vivo. METHODS: 19-peptide was expressed in bacteria and purified with Sephadex G-15. SGC7901 gastric carcinoma cells and human umbilical-vein endothelial cells (HUVECs) were exposed to 19-peptide in vitro, and their viability was evaluated by biochemical and histopathological analysis. In vivo, pieces of solid tumor derived from SGC7901 cells were inoculated into the gastric serosa of 36 nude mice, with a biological glue to hold them in place. Twenty-eight days after injection of 19-peptide, the mice were killed. The tumors were measured and examined by western blotting, histopathology, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. RESULTS: 19-peptide induced apoptosis of many SGC7901 cells but few HUVECs in vitro. In vivo, after the application of 19-peptide, significant tumor cell apoptosis was observed in the center of the tumors, tumor volume was reduced significantly (P < 0.001), and the invasion and migration of cancer cells was reduced. PTEN was increased in the treatment group and phospho-Akt (pAkt) was decreased in the control group. CONCLUSIONS: These results suggest that 19-peptide inhibits the growth and metastases of poorly differentiated gastric carcinoma cells, primarily by inducing apoptosis. The apoptotic mechanism could be related to anoikis and the PTEN/Akt pathway.
Assuntos
Antineoplásicos/farmacologia , Autoantígenos/farmacologia , Carcinoma/tratamento farmacológico , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/farmacologia , Fragmentos de Peptídeos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To compare the efficacy and complications of the Shang Ring circumcision with those of conventional surgical procedures. METHODS: A total of 724 patients, 521 with redundant prepuce and 203 with phimosis, were randomly assigned to receive the Shang Ring circumcision (n = 402) and conventional surgical procedures (n = 322). Comparisons were made between the two groups in the surgical duration, blood loss, pain score, as well as postoperative complications, satisfaction with the penile appearance, and the quality of sexual life. RESULTS: The surgical duration, blood loss, postoperative satisfaction and IIRF-5 score were (4.70 +/- 1.30) min, (2.60 +/- 1.80) ml, 99.50% (400/402) and 23.45 +/- 3.43, respectively, in the Shang Ring group as compared with (25.6 +/- 8.3) min, (11.20 +/- 3.50) ml, 69.57% (224/322) and 23.12 +/- 3.26 in the conventional surgery group, with statistically significant differences in the first three parameters (P < 0.01), but not in IIRF-5 score (P > 0.05). CONCLUSION: Compared with the conventional surgical procedures, the Shang Ring circumcision has the advantages of shorter operation time, less blood loss, mild pain, fewer complications, better penile appearance, lower expenses, and higher satisfaction and acceptance of the patients.
Assuntos
Circuncisão Masculina/métodos , Pênis/cirurgia , Fimose/cirurgia , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and Aß1-42-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the Aß1-42-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from Aß1-42 treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Saponinas/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Células PC12 , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Ratos , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Saponinas/síntese química , Saponinas/química , Relação Estrutura-AtividadeRESUMO
Human papillomavirus (HPV) is an etiological risk factor for oropharyngeal squamous cell carcinomas (OPSCC). Our study investigates the prevalence, prognostic, and clinicopathologic features of HPV-related oropharyngeal cancer in Northeast China and elucidates the involvement of p16 in the tumorigenesis and progression of OPSCC. Specimens from 1470 OPSCC patients collected from 2000 to 2016 were analyzed using the status of HPV by polymerase chain reaction (PCR) and p16 immunohistochemistry. Overexpression of p16 was observed in 81 (5.51%) of the 1470 cases, and HPV positive was present in 78 cases (5.31%) of the 1470 cases. HPV positive and p16 overexpression have a good concordance. However, we found that the etiological fraction of HPV in cancers of the OPSCCs was obviously lower in Northeast China than other cohorts previously reported. Interestingly, nearly 89% of patients with p16 expression were smokers, and nearly 70% of patients with p16 expression had a history of alcohol. Our study also demonstrates that p16 expression is significantly associated with early stage primary OPSCCs and the patients with p16 expression tend to show better survival following surgery and radiotherapy.
Assuntos
Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Neoplasias Bucais/metabolismo , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Biomarcadores Tumorais/genética , China/epidemiologia , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/genética , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Orofaringe/química , Orofaringe/patologia , Papillomaviridae , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de RiscoRESUMO
CONCLUSION: This study demonstrated that the common immunological mechanism, which involves aberration of immunoglobulin and T-cell distribution in histologically distinctive tonsils, may be associated with the pathogenesis of tonsillar focal infection. OBJECTIVES: Tonsillar focal infection comprises a group of relatively common diseases combined with chronic tonsillar infection, is associated with unusual immune responses in tonsils, and may cause lesions in another distant target organ. This study aimed to investigate the distribution of inflammatory T cells and T-cell regulatory elements, such as programmed cell death-1 (PD-1) and Fork head box protein 3 (Foxp3), immunoglobulin production, and histological characteristics in tonsils from patients with tonsillar focal infection. METHODS: Immunohistochemistry and reverse transcription-polymerase chain reaction (PCR) were used to compare the expression of CD8(+) T cells, immunoglobulins, and cytokines associated with immunoglobulin production in the tonsils of patients with IgA nephropathy (IgAN), palmoplantar pustulosis (PPP), rheumatoid arthritis (RA), and chronic tonsillitis. RESULTS: The overexpression of CD8(+) T cells combined with decreased expression of Foxp3 and PD-1 and the aberration of immunoglobulin production, which may be due to the elevated expression of activation-induced deaminase (AID), B-cell-activating factor of the TNF family (BAFF), supporting isotype switching, and B-cell survival in the histologically distinctive tonsils.
Assuntos
Artrite Reumatoide/imunologia , Linfócitos T CD8-Positivos/fisiologia , Infecção Focal/imunologia , Glomerulonefrite por IGA/imunologia , Imunoglobulinas/metabolismo , Tonsilite/imunologia , Adulto , Artrite Reumatoide/metabolismo , Fator Ativador de Células B/metabolismo , Antígenos CD8/metabolismo , Microambiente Celular , Citidina Desaminase/metabolismo , Feminino , Infecção Focal/metabolismo , Infecção Focal/patologia , Fatores de Transcrição Forkhead/metabolismo , Glomerulonefrite por IGA/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/patologia , Receptor de Morte Celular Programada 1/metabolismo , Proteínas/metabolismo , Sindecana-1/metabolismo , Tonsilite/metabolismo , Tonsilite/patologiaRESUMO
Immunoglobulin A nephropathy (IgAN) is characterized by a qualitative abnormality of IgA in the circulation and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils. Follicular dendritic cell-secreted protein (FDC-SP), a small novel secretory protein that may regulate the induction of B-cell responses, has been suggested to control IgA production. Given this background, this study investigated the expression of FDC-SP and its correlation with IgA production in the tonsils of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to compare the expression of FDC-SP in the tonsils of IgAN patients with tonsillitis and of non-IgAN patients with chronic tonsillitis. The location of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. We found that FDC-SP expression significantly decreased and was correlated negatively with enhanced IgA production in the tonsils of IgAN patients. FDC-SP secreted by follicular dendritic cells may act on germinal center B cells and participate in the modulation of IgA generation in the tonsils. Our study demonstrated that FDC-SP may be involved in IgA production in the tonsils of IgAN patients, making this protein an attractive candidate immunomodulator, and highlighting a promising strategy for therapeutic intervention in IgAN.