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1.
Ann Surg Oncol ; 31(4): 2679-2688, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142258

RESUMO

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Pontuação de Propensão , Perda Sanguínea Cirúrgica , Resultado do Tratamento , Gastrectomia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
2.
J Org Chem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323758

RESUMO

Herein, we report a single-step, multicomponent approach to versatile γ-lactams through dual photoredox/nickel-catalyzed dicarbofunctionalization of α,ß-unsaturated γ-butyrolactam. This reaction utilized alkyl trimethylgermanium as a radical precursor and acyl chloride as the electrophile, demonstrating remarkable functional group compatibility.

3.
Arch Virol ; 168(9): 227, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566243

RESUMO

Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.


Assuntos
Infecções por Coronavirus , Coronavirus Felino , Coronavirus Felino/genética , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Doenças do Gato/virologia , Animais , Gatos , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas M de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/genética , Masculino , Feminino
4.
Toxicol Appl Pharmacol ; 414: 115426, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524445

RESUMO

Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1ß mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NFκB (P65) phosphorylation, and inhibited NFκB (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of IκBα phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+]i; however, CCCP showed no significant effect on IκBα phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.


Assuntos
Inflamassomos/agonistas , Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Desacopladores/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Cálcio/metabolismo , Carbonil Cianeto m-Clorofenil Hidrazona/toxicidade , Citocinas/genética , Citocinas/metabolismo , Diaminas/toxicidade , Humanos , Inflamassomos/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Inibidor de NF-kappaB alfa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Niclosamida/toxicidade , Oxidiazóis/toxicidade , Fosforilação , Pirazinas/toxicidade , Células RAW 264.7 , Células THP-1
5.
Clin Exp Hypertens ; 42(1): 75-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30701983

RESUMO

Objectives: Recently, serum uric acid (UA) has emerged as an important independent risk factor for adverse outcomes in hypertension. The aim of the study was to evaluate the relationship between UA levels and ascending aortic dilatation (AAD) in newly diagnosed nondiabetic hypertensive subjects.Methods: A total of 818 patients with a new diagnosis of hypertension for which they had never received treatment were enrolled in this cross-sectional study. All patients underwent comprehensive transthoracic echocardiography measurement. AAD was defined as a diameter of ascending aorta equal to or more than 35 mm.Results: There were 302 patients with AAD (mean age 69 ± 11 years; 157 male) and 516 subjects with normal ascending aorta diameters (mean age 64 ± 12 years; 158 male). The correlation analysis pointed out positive correlations between ascending aorta size and serum UA levels (r = 0.30, P<0.001). In multiple logistic regression analysis, the OR of a 1 mg/dL increase in serum UA was 1.29(95% CI, 1.18 to 1.43; P < 0.001) for AAD. In reference to the first quartile, the prevalence of AAD increased such that the OR for the fourth quartile was 4.03 (95% CI, 2.38 to 6.82; P for trend < 0.001) of the serum UA concentration. The optimal UA cutoff value for detecting AAD was 6.45 mg/dL, based on receiver operating characteristic curve analysis with a sensitivity of 68.0% and a specificity of 70.0%.Conclusion: Serum UA concentration was significantly associated with AAD prevalence in newly diagnosed nondiabetic hypertensive patients.


Assuntos
Aorta/patologia , Hipertensão/sangue , Ácido Úrico/sangue , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Estudos Transversais , Dilatação Patológica/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
6.
Plant Dis ; 104(10): 2665-2668, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32749946

RESUMO

Sugarcane white leaf (SCWL) is a devastating sugarcane (Saccharum officinarum) disease caused by a 16SrXI group phytoplasma, which is extremely harmful to sugarcane production. To determine the occurrence of SCWL in different varieties in 2018, we conducted a field survey and performed nested PCR detection of SCWL phytoplasma in cane-planting areas of Mangweng and Hepai in Gengma, Yunnan province, which are the areas most severely affected by SCWL in China. The results of the field survey showed that the symptomatic incidence of SCWL differed among varieties. The mean symptomatic incidence of SCWL on variety Yuetang60 was the highest (73.50%), and it was the lowest on Liucheng05-136 (13.67%). Using nested PCR, the SCWL phytoplasma was detected in symptomatic plants of all varieties more than 90% of the time; the SCWL phytoplasma was detected in 91 and 97% of symptomatic plants of Yingyu91-59 and Liucheng05-136 varieties, respectively. The SCWL phytoplasma was detected by PCR in 82% of the asymptomatic plant samples. The results of this study showed that field survey based on white leaf symptoms did not accurately reflect the actual occurrence of the SCWL phytoplasma.


Assuntos
Saccharum , China , Incidência , Doenças das Plantas , Reação em Cadeia da Polimerase , Inquéritos e Questionários
7.
BMC Vet Res ; 15(1): 131, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060564

RESUMO

BACKGROUND: Hepatitis E virus (HEV) is one of most important zoonotic viruses, and it can infect a wide range of host species. Avian HEV has been identified as the aetiological agent of big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens. HEV infection is common among chicken flocks in China, and there are currently no practical measures for preventing the spread of the disease. The predominant avian HEV genotype circulating in China have been identified as genotype 3 strains, although some novel genotypes have also been identified from chicken flocks in China. RESULTS: In this study, we used a meta-transcriptomics approach to identify a new subtype of genotype 3 avian HEV in broiler chickens at a poultry farm located in Shenzhen, Guangdong Province, China. The complete genome sequence of the avian HEV, designated CaHEV-GDSZ01, is 6655-nt long, including a 5' UTR of 24 nt and a 3' UTR of 125 nt (excluding the poly(A) tail), and contains three open reading frames (ORFs). Sequence analysis indicated that the complete ORF1 (4599 nt/1532 aa), ORF2 (1821 nt/606 aa) and ORF3 (264 nt/87 aa) of CaHEV-GDSZ01 share the highest nucleotide sequence identity (85.8, 86.7 and 95.8%, respectively) with the corresponding ORFs of genotype 3 avian HEV. Phylogenetic analyses further demonstrated that the avian HEV identified in this study is a new subtype of genotype 3 avian HEV. CONCLUSIONS: Our results demonstrate that a new subtype of genotype 3 avian HEV is endemic in Guangdong, China, and could cause high mortality in infected chickens. This study also provides full genomic data for better understanding the evolutionary relationships of avian HEV circulating in China. Altogether, the results presented in this study suggest that more attention should be paid to avian HEV and its potential disease manifestation.


Assuntos
Perfilação da Expressão Gênica/veterinária , Hepatite Viral Animal/virologia , Hepevirus/genética , Doenças das Aves Domésticas/virologia , Animais , Galinhas , China/epidemiologia , Genótipo , Hepatite Viral Animal/epidemiologia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/mortalidade , Infecções por Vírus de RNA/epidemiologia , Infecções por Vírus de RNA/veterinária , Infecções por Vírus de RNA/virologia
8.
BMC Vet Res ; 15(1): 143, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077188

RESUMO

BACKGROUND: Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5-50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. RESULTS: Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5' non-coding region (GCUUUU) and 3' non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, µA, µNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. CONCLUSIONS: The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses.


Assuntos
Doenças das Aves/virologia , Orthoreovirus Aviário/classificação , Orthoreovirus Aviário/genética , Filogenia , Infecções por Reoviridae/veterinária , Animais , China , Sequência Conservada , Patos , Genoma Viral/genética , Infecções por Reoviridae/virologia , Análise de Sequência de DNA
9.
Nucleic Acids Res ; 44(8): 3629-42, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-26704979

RESUMO

Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.


Assuntos
RNA Helicases DEAD-box/metabolismo , Dano ao DNA , Histonas/metabolismo , Ribonuclease III/metabolismo , Sirtuínas/metabolismo , Linhagem Celular , Cromatina/metabolismo , Cisplatino/toxicidade , RNA Helicases DEAD-box/antagonistas & inibidores , Doxorrubicina/toxicidade , Células HEK293 , Humanos , Radiação Ionizante , Ribonuclease III/antagonistas & inibidores
10.
Zhonghua Nan Ke Xue ; 24(4): 331-334, 2018 Apr.
Artigo em Zh | MEDLINE | ID: mdl-30168953

RESUMO

OBJECTIVE: To investigate the diagnosis and management of penile fracture. METHODS: From June 1993 to May 2017, 46 cases of penile fracture were treated in our hospital, averaging 33.5 (25-42) years of age and 3.45 (1-10) hours in duration, of which 41 occurred during sexual intercourse, 4 during masturbation and 1 during prone sleeping, 4 with hematuria, but none with dysuria or urethral bleeding. Hematoma was confined to the penis. Emergency surgical repair was performed for all the patients, 45 under spinal anesthesia and 1 under local anesthesia, 16 by coronal proximal circular incision and the other 30 by local longitudinal incision according to the rupture location on ultrasonogram. The tunica albuginea ruptures averaged 1.31 (0.5-2.5) cm in length, which were sutured in the "8" pattern for 6 cases and with the 3-0 absorbable thread for 18 cases. The skin graft or negative pressure drainage tube was routinely placed, catheters indwelt, and gauze used for early pressure dressing. In the recent few years, elastic bandages were employed for 3-5 days of pressure dressing and antibiotics administered to prevent infection. The stitches and catheter were removed at 7 days after surgery. RESULTS: Short-term postoperative foreskin edema occurred in 14 of the 16 cases of circular degloving incision, but no postoperative complications were observed in any of the cases of local incision. Twenty-eight of the patients completed a long-term follow-up of 49.4 (10-125) months, which revealed good erectile function, painless erection, and satisfactory sexual intercourse. CONCLUSIONS: For most penile fractures, local longitudinal incision is sufficient for successful repair of the tunica albuginea, with mild injury, no influence on the blood supply or lymph reflux, and a low rate complications. It therefore is obviously advantageous over circular degloving incision except when the cavernous body of urethra is to be explored, which necessitates circular degloving incision below the coronal groove.


Assuntos
Pênis/lesões , Ruptura/cirurgia , Ferida Cirúrgica , Adulto , Coito , Edema/etiologia , Hematoma/diagnóstico , Hematoma/etiologia , Humanos , Masculino , Masturbação/complicações , Ereção Peniana , Complicações Pós-Operatórias/etiologia , Ruptura/diagnóstico , Ruptura/etiologia , Ultrassonografia , Uretra/cirurgia
11.
Carcinogenesis ; 38(9): 873-882, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911000

RESUMO

DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regulates NHEJ and chemosensitivity in colon cancer cells. Using our recently developed NHEJ assay, we found that DSB introduction by I-SceI cleavage leads to Dicer upregulation. Dicer knockdown increased SIRT7 binding and decreased the level of H3K18Ac (acetylated lysine 18 of histone H3) at DSB sites, thereby repressing the recruitment of NHEJ factors to DSB sites and inhibiting NHEJ. Dicer overexpression reduced SIRT7 binding and increased the level of H3K18Ac at DSB sites, promoting the recruitment of NHEJ factors to DSBs and moderately enhancing NHEJ. Dicer knockdown and overexpression increased and decreased, respectively, the chemosensitivity of colon cancer cells. Dicer protein expression in colon cancer tissues of patients was directly correlated with chemoresistance. Our findings revealed a function of Dicer in NHEJ-mediated DSB repair and the association of Dicer expression with chemoresistance in colon cancer patients.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , RNA Helicases DEAD-box/fisiologia , Reparo do DNA por Junção de Extremidades/genética , Resistencia a Medicamentos Antineoplásicos/genética , Ribonuclease III/fisiologia , Animais , RNA Helicases DEAD-box/genética , Quebras de DNA de Cadeia Dupla , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Células HCT116 , Células HEK293 , Histonas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Ribonuclease III/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo
12.
Int J Syst Evol Microbiol ; 66(1): 487-491, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26508111

RESUMO

Sugar cane white leaf (SCWL) is a serious disease caused by phytoplasmas. In this study, we performed nested PCR with phytoplasma universal primer pairs (P1/P7 and R16F2n/R16R2) for the 16S rRNA gene to detect SCWL phytoplasmas in 31 SCWL samples collected from Baoshan and Lincang, Yunnan, China. We cloned and sequenced the nested PCR products, revealing that the 16S rRNA gene sequences from 31 SCWL samples were all 1247 bp in length and shared more than 99 % nucleotide sequence similarity with the 16S rRNA gene sequences of SCWL phytoplasmas from various countries. Based on the reported 16S rRNA gene sequence data from SCWL isolates of various countries, we conducted phylogenetic and virtual RFLP analysis. In the resulting phylogenetic tree, all SCWL isolates clustered into two branches, with the Lincang and Baoshan SCWL phytoplasma isolates belonging to different branches. The virtual RFLP patterns show that phytoplasmas of the Lincang branch belong to subgroup 16SrXI-B. However, the virtual RFLP patterns revealed by HaeIII digestion of phytoplasmas of the Baoshan branch differed from those of subgroup 16SrXI-B. According to the results of phylogenetic and virtual RFLP analysis, we propose that the phytoplasmas of the Baoshan branch represent a new subgroup, 16SrXI-D. These findings suggest that SCWL is caused by phytoplasmas from group 16SrXI, including subgroup 16SrXI-B and a new subgroup, 16SrXI-D.


Assuntos
Filogenia , Phytoplasma/classificação , Doenças das Plantas/microbiologia , Saccharum/microbiologia , China , DNA Bacteriano/genética , Phytoplasma/genética , Phytoplasma/isolamento & purificação , Folhas de Planta/microbiologia , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
13.
Proteomics ; 14(4-5): 566-78, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24339160

RESUMO

Aluminum (Al) toxicity is a major constraint for plant root development and growth as well as crop yield in acidic soils, which constitute approximately 40% of the potentially arable lands worldwide. The mechanisms of Al tolerance in plants are not well understood. As a whole systems approach, proteomic techniques have proven to be crucial as a complementary strategy to explore the mechanism in Al toxicity. Review here focuses on the potential of proteomics to unravel the common and plant species-specific changes at proteome level under Al stress, via comparative analysis of the Al-responsive proteins uncovered by recent proteomic studies using 2DE. Understanding the mechanisms of Al tolerance in plants is critical to generate Al resistance crops for developing sustainable agriculture practices, thereby contributing to food security worldwide.


Assuntos
Alumínio/toxicidade , Proteínas de Plantas/biossíntese , Proteômica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo
14.
Drug Dev Ind Pharm ; 39(11): 1712-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23062067

RESUMO

Characterization and antitumor activity of basic fibroblast growth factor-mediated active targeting doxorubicin microbubbles (bFGF-DOX-MB) were investigated. Pluronic F68 with chemical conjugation of doxorubicin (DOX-P) and peptide KRTGQYKLC-conjugated DSPE-PEG2000 were prepared. bFGF-DOX-MB had a normal distribution of particle size, with average particle size of 2.7 µm. Using A549 mouse model, bFGF-DOX-MB combined ultrasound showed the best inhibition effect on tumor volume growth among all the test groups. Similar conclusion was obtained from experimental measurements of tumor weight change and blood cell count. From the results, chemotherapeutic drug inhibition on tumor growth could be enhanced by local ultrasound combined with active targeting bFGF-DOX-MB, which might provide a potential application for ultrasound-mediated chemotherapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Microbolhas/uso terapêutico , Oligopeptídeos/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/efeitos adversos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/efeitos adversos , Estudos de Viabilidade , Fator 2 de Crescimento de Fibroblastos/efeitos adversos , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Microbolhas/efeitos adversos , Proteínas de Neoplasias/metabolismo , Oligopeptídeos/efeitos adversos , Oligopeptídeos/química , Oligopeptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/uso terapêutico , Domínios e Motivos de Interação entre Proteínas , Distribuição Aleatória , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Front Physiol ; 14: 1349106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38269063

RESUMO

The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis-key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in Procambarus clarkii, followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24 h post-injection (hpi) in the epidermis and at 48 hpi in the gills. At 24 hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48 hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24 hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH's impact on the epidermis was prominent at 24 hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48 hpi. This differential CHH effect between gills and epidermis in P. clarkii provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.

16.
Br J Pharmacol ; 180(1): 62-79, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36082580

RESUMO

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.


Assuntos
Aterosclerose , Camundongos , Animais , Preparações Farmacêuticas/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Mitocôndrias/metabolismo , Nitrocompostos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo
17.
Cell Rep Med ; 4(2): 100911, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36657446

RESUMO

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Medicina de Precisão , Organoides/patologia
18.
Drug Dev Ind Pharm ; 38(3): 365-71, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21854252

RESUMO

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes-propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index = 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.


Assuntos
Curcumina/química , Lipossomos/química , Veículos Farmacêuticos/química , Propilenoglicol/química , Animais , Disponibilidade Biológica , Células Cultivadas , Química Farmacêutica , Cricetinae , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Tamanho da Partícula
19.
Drug Dev Ind Pharm ; 38(9): 1090-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22188116

RESUMO

Experiments in vitro and in vivo were designed to investigate tumor growth inhibition of chemotherapeutics-loaded liposomes enhanced by acoustic cavitation. Doxorubicin-loaded liposomes (DOX liposomes) were used in experiments to investigate acoustic cavitation mediated effects on cell viability and chemotherapeutic function. The influence of lingering sensitive period after acoustic cavitation on tumor inhibition was also investigated. Animal experiment was carried out to verify the practicability of this technique in vivo. From experiment results, blank phospholipid-based microbubbles (PBM) combined with ultrasound (US) at intensity below 0.3 W/cm² could produce acoustic cavitation which maintained cell viability at high level. Compared with DOX solution, DOX liposomes combined with acoustic cavitation exerted effective tumor inhibition in vitro and in vivo. The lingering sensitive period after acoustic cavitation could also enhance the susceptibility of tumor to chemotherapeutic drugs. DOX liposomes could also exert certain tumor inhibition under preliminary acoustic cavitation. Acoustic cavitation could enhance the absorption efficiency of DOX liposomes, which could be used to reduce DOX adverse effect on normal organs in clinical chemotherapy.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Veículos Farmacêuticos/química , Terapia por Ultrassom/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Transporte Biológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Lecitinas/química , Lipossomos , Masculino , Camundongos , Camundongos Nus , Microbolhas , Sonicação , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Zhonghua Yi Xue Za Zhi ; 92(23): 1615-7, 2012 Jun 19.
Artigo em Zh | MEDLINE | ID: mdl-22944130

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of radiation plus erlotinib in patients with esophageal cancer older than 70 years. METHODS: Radiotherapy was prescribed at a daily fraction of 2.0 Gy up to a total dose of 60 Gy over 6 weeks. Concurrent erlotinib was administrated at a dose of 150 mg daily at days 1-42. Acute toxicities were assessed by the criteria of Radiation Therapy Oncology Group (RTOG) and National Cancer Institute (NCI). The results were analyzed by the software SPSS 17.0. RESULTS: A total of 33 patients were enrolled. The median survival time was 16.3 ± 8.6 months (95%CI 0.0 - 33.3) and the 1-and 2-year overall survival rates were 66.3% and 49.7% respectively. The media progression-free survival was 16.7 ± 7.1 months (95%CI 2.9 - 30.5) and the 1- and 2-year local control rates 73.3% and 54.9% respectively. Most toxicities were of grade 1-2 and manageable. CONCLUSION: The combined regimen of radiation and erlotinib is effective and safe in elder patients aged > 70 years with esophageal cancer. However the results of our study should be confirmed in randomized controlled trials of a larger sample size.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Quinazolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Cloridrato de Erlotinib , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico
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