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1.
Genome Res ; 33(10): 1690-1707, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37884341

RESUMO

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.


Assuntos
Metagenoma , Microbiota , Ovinos/genética , Animais , Transcriptoma , Rúmen , Ruminantes/genética
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 838-842, 2023 Oct 18.
Artigo em Zh | MEDLINE | ID: mdl-37807737

RESUMO

OBJECTIVE: To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone. METHODS: The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status. RESULTS: Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer. CONCLUSION: tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
3.
J Nanobiotechnology ; 20(1): 369, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953798

RESUMO

BACKGROUND: Immunosuppressive tumor immune microenvironment (TIME) lowers immunotherapy effectiveness. Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy. METHODS: A triblock copolymeric micelle (NanoPCPT+PIMDQ) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of NanoPCPT+PIMDQ was assessed both in vitro and in vivo. RESULTS: NanoPCPT+PIMDQ is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) NanoPCPT+PIMDQ first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3+ Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME. CONCLUSION: This pH/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy.


Assuntos
Camptotecina , Neoplasias , Camptotecina/farmacologia , Linhagem Celular Tumoral , Humanos , Imunoterapia , Micelas , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Receptor 7 Toll-Like , Microambiente Tumoral
4.
BMC Urol ; 19(1): 57, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262284

RESUMO

BACKGROUND: Clinical studies assessing the feasibility and accuracy of three stone scoring systems's (SSSs: Guy's stone score, CROES nomogram and S.T.O.N.E nephrolithometry scoring system) have reported contradictory outcomes. This systematic evaluation was performed to obtain comprehensive evidence with regard to the feasibility and accuracy of three SSSs. METHODS: A systematic search of Embase, Pubmed, Medline, and the Cochrane Library was conducted to identify studies that compared three SSSs up to Mar 2018. Patients were categorized according to stone free (SF) and no-stone free (NSF), Outcomes of interest included perioperative variables, stone-free rate (SFR), and complications. RESULTS: Ten studies estimating three SSSs were included for meta-analysis. The results showed that SF patients had a significantly lower proportion of male (OR = 1.48, P = 0.0007), lower stone burden (WMD = -504.28, P < 0.0001), fewer No of involved calyces (OR = -1.23, P = 0.0007) and lower proportion of staghorn stone (OR = 0.33, P < 0.0001). Moreover, SF patients had significantly lower score of Guy score (WMD = -0.64, P < 0.0001), but, S.T.O.N.E. score (WMD = -1.23, P < 0.0001) and a higher score of CROES nomogram (WMD = 29.48, P = 0.003). However, the comparison of area under curves (AUC) of predicting SFR indicated that there was no remarkable difference between three SSSs. Nonetheless, Guy score was the only stone scoring system that predicted complications after PCNL (WMD = -0.29, 95% CI: - 0.57 to - 0.02, P = 0.03). CONCLUSIONS: Our meta-analysis indicated that the three SSSs were equally, feasible and accurate for predicting SFR after PCNL. However, Guy score was the only stone scoring system that predicted complications after PCNL.


Assuntos
Cálculos Renais/diagnóstico , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença , Humanos , Nefrolitotomia Percutânea/tendências , Valor Preditivo dos Testes , Estudos Retrospectivos
5.
Angew Chem Int Ed Engl ; 57(44): 14493-14497, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-29419912

RESUMO

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E-oximino α-diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral RhII complex and a subsequent intermolecular 1,3-dipolar cycloaddition catalyzed by a chiral N,N'-dioxide NdIII Lewis acid complex. The enantioselectively catalyzed transformation has broad scope and yields the desired spirotropanyl oxindole cycloadducts in high yields and with very high enantio- and diastereoselectivity.


Assuntos
Metais/química , Oxindóis/química , Catálise , Ácidos de Lewis/química , Estereoisomerismo
6.
Angew Chem Int Ed Engl ; 57(43): 14250-14254, 2018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30203905

RESUMO

Axially chiral 4-arylisoquinolones are endowed with pronounced bioactivity, and methods for their efficient synthesis have gained widespread attention. However, enantioselective synthesis of axially chiral 4-arylisoquinolones by means of C-H activation has not been reported to date. Described here is a rhodium (III)-catalyzed C-H bond activation and annulation for the atroposelective synthesis of axially chiral 4-arylisoquinolones. The method employs chiral cyclopentadienyl ligands embodying a piperidine ring as backbone and yields the atropisomers with good to excellent yields and enantioselectivity. Biological relevance of the 4-arylisoquinolones was demonstrated by their investigation in different cellular assays, leading to the discovery of novel non-SMO (SMO= smoothened) binding Hedgehog pathway inhibitors.


Assuntos
Proteínas Hedgehog/antagonistas & inibidores , Compostos Heterocíclicos/síntese química , Quinolonas/síntese química , Animais , Catálise , Linhagem Celular , Compostos Heterocíclicos/química , Ligantes , Camundongos , Camundongos Endogâmicos C3H , Quinolonas/química , Ródio/química , Estereoisomerismo
7.
Org Biomol Chem ; 13(3): 697-701, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25429854

RESUMO

A palladium(II)-catalyzed ß-methylene C(sp(3))-H bond alkenylation of acyclic aliphatic amides with alkenyl halides has been developed. Both (E)-olefins and (Z)-olefins can be readily accessed using this method and a possible (Z)/(E)-olefin isomerization pathway is proposed. A solvent effect-promoted sequential C(sp(3))-H bond alkenylation and C(sp(2))-H bond alkenylation was also studied, and can provide a convenient route to novel diene compounds.


Assuntos
Alcenos/química , Amidas/química , Paládio/química , Catálise , Estrutura Molecular , Estereoisomerismo
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(4): 586-91, 2015 Aug 18.
Artigo em Zh | MEDLINE | ID: mdl-26284390

RESUMO

OBJECTIVE: To compare the diagnostic accuracy of five internationally used indolent prostate cancer screen protocols in Chinese prostate cancer patients. METHODS: Retrospective analysis was made of the consecutive cohort of 314 patients, from Jan. 2006 to Apr. 2014, who had both prostate biopsy and radical prostatectomy in Peking University First Hospital. The Gleason score≤6, pT2, tumor volume≤0.5 mL, margin negative and lymph nodes negative were defined as indolent prostate cancer. The predictive value of five indolent screen criteria including Epstein, Memorial Sloan-Kettering Cancer Center (MSKCC), Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco (UCSF), and University of Miami (UM) were evaluated in Chinese prostate cancer patients. Measures of diagnostic accuracy and areas under the receiver-operating curve (AUC) were calculated for each protocol and compared. RESULTS: A total of 16% (49 cases) of the patients met the inclusion criteria of at least one protocol, including 24 cases in Epstein, 33 cases in MSKCC, 28 cases in PRIAS, 34 cases in UCSF, and 22 cases in UM. Three percent were eligible for all the studied criteria. UCSF and MSKCC protocols had the highest sensitivity and specificity than the others. The Epstein and PRIAS protocols demonstrated acceptable positive predictive value, but the specificity and sensitivity were inefficient. The UM protocol was performed unsatisfiedly on sensitivity, positive predictive value and AUC. A strict limited protocol which contained all the five protocols could not improve the predictive accuracy. CONCLUSION: The UCSF protocol had better diagnostic accuracy than the others, but the results were not satisfied. A further investigation on indolent prostate cancer screening in Chinese patients is needed.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico , Povo Asiático , Biópsia , Humanos , Masculino , Gradação de Tumores , Prostatectomia , Estudos Retrospectivos
9.
Zool Res ; 45(2): 233-241, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38287904

RESUMO

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.


Assuntos
Proteínas do Citoesqueleto , Defeitos do Tubo Neural , Animais , Proteínas do Citoesqueleto/metabolismo , Tubo Neural/metabolismo , Macaca fascicularis , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/veterinária , Células Neuroepiteliais/metabolismo , Ácido Fólico/metabolismo , Organoides , Citoesqueleto
10.
Org Biomol Chem ; 11(14): 2318-22, 2013 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-23429608

RESUMO

A unique Rh(II) and Ru(II) catalyzed C-H oxygenation of aryl ketones and other arenes has been developed for the facile synthesis of diverse functionalized phenols. The reaction demonstrates excellent reactivity, regio- and chemoselectivity, good functional group compatibility and high yields. The practicality of this method has been proved by gram-scale synthesis of a few different 2-acylphenols. Its utility has been well exemplified in further applications in heterocycle synthesis and direct modifications of drug Fenofibrate.


Assuntos
Fenóis/química , Ródio/química , Rutênio/química , Acilação , Catálise , Cetonas/química , Estrutura Molecular , Oxigênio/química , Estereoisomerismo
11.
Reprod Fertil Dev ; 25(4): 609-16, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23594385

RESUMO

The goal of this study was to investigate the effect of cryopreservation on oocytes at different times after intracytoplasmic sperm injection (ICSI) and parthenogenetic activation. The study was performed in mouse oocytes fertilised by ICSI, or in artificially-activated oocytes, which were cryopreserved immediately, one hour or five hours later through slow-freezing. After thawing, the rates of survival, fertilisation-activation, embryonic development of oocytes-zygotes and changes in the cytoskeleton and ploidy were observed. Our results reveal a significant difference in survival rates of 0-, 1- and 5-h cryopreserved oocytes following ICSI and artificial activation. Moreover, significant differences in two pronuclei (PN) development existed between the 0-, 1- and 5-h groups of oocytes frozen after ICSI, while the rates of two-PN development of activated oocytes were different between the 1-h and 5-h groups. Despite these initial differences, there was no difference in the rate of blastocyst formation from two-PN zygotes following ICSI or artificial activation. However, compared with ICSI or artificially-activated oocytes cryopreserved at 5h, many oocytes from the 0- and 1-h cryopreservation groups developed to zygotes with abnormal ploidy; this suggests that too little time before cryopreservation can result in some activated oocytes forming abnormal ploidy. However, our results also demonstrate that spermatozoa can maintain normal fertilisation capacity in frozen ICSI oocytes and the procedure of freeze-thawing did not affect the later development of zygotes.


Assuntos
Núcleo Celular/fisiologia , Criopreservação/métodos , Desenvolvimento Embrionário/fisiologia , Microtúbulos/fisiologia , Oócitos/fisiologia , Animais , Aberrações Cromossômicas , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Oócitos/citologia , Partenogênese/fisiologia , Propilenoglicol , Injeções de Esperma Intracitoplásmicas/métodos , Análise de Sobrevida , Fatores de Tempo
12.
Angew Chem Int Ed Engl ; 52(51): 13606-10, 2013 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-24214420

RESUMO

All the hype: The title reaction has been developed for the facile synthesis of a variety of complex alkyl ethers. Cyclic hypervalent iodine (I(3+) ) reagents serve as oxidants for this unique CH alkoxylation reaction. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. Q=8-aminoquinoline-derived auxiliary.


Assuntos
Iodo/química , Oxidantes/química , Paládio/química , Catálise , Estereoisomerismo
13.
Adv Healthc Mater ; 12(31): e2301517, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37689990

RESUMO

Photodynamic therapy is a promising cancer therapeutic method that can damage DNA via photoinduced reactive oxygen species production. However, tumor cells can initiate DNA repair pathways to resist oxidative damage. In this study, a nuclear-targeted photosensitizer PARP-PS with a poly (ADP-ribose) polymerase 1 (PARP1) inhibitory effect is developed based on the reported PARP1 inhibitor, rucaparib. As a dual-mode DNA-damaging agent, PARP-PS damages DNA upon photoirradiation and enhances oxidative DNA damage by blocking the DNA repair pathway via PARP1 inhibition and degradation. Both in vitro and in vivo investigations demonstrate that PARP-PS exhibits high antitumor activity with few side effects in breast cancer. In addition, PARP-PS can act as an immunogenic cell death inducer to activate immune responses characterized by the promotion of cytotoxic T lymphocyte activation and tumor infiltration. Therefore, PARP-PS is a potential multimodal antitumor agent with synergistic phototherapeutic, chemotherapeutic, and immunotherapeutic effects.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Dano ao DNA , Neoplasias da Mama/tratamento farmacológico , DNA , Linhagem Celular Tumoral , Reparo do DNA , Poli(ADP-Ribose) Polimerase-1/genética
14.
Eur J Med Chem ; 255: 115418, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37119664

RESUMO

Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.


Assuntos
Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Oxigênio Singlete/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fotoquimioterapia/métodos
15.
J Med Chem ; 66(15): 10265-10272, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37421416

RESUMO

In this work, we described a photocatalytic approach, termed ligand-directed photodegradation of interacting proteins (LDPIP), for efficient protein-protein heterodimer degradation. This LDPIP approach utilizes a combination of a photosensitizing protein ligand and appropriate light and molecular oxygen to induce oxidative damage to the ligand-binding protein as well as its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was rationally designed based on the FDA-approved HER2 inhibitor lapatinib to efficiently degrade HER2 together with its interacting protein partner HER3, which is thought to induce HER2-targeted therapy resistance and difficult to target by small molecules. HER-PS-I exhibited excellent anticancer activity against drug-resistant MDA-MB-453 cells and its three-dimensional multicellular spheroids. We hope that this LDPIP approach would find more applications in degrading proteins that are thought undruggable or difficult to drug.


Assuntos
Antineoplásicos , Lapatinib/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Trastuzumab , Receptor ErbB-2/metabolismo , Ligantes , Fotólise , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptor ErbB-3/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(4): 568-70, 2012 Aug 18.
Artigo em Zh | MEDLINE | ID: mdl-22898848

RESUMO

OBJECTIVE: To analyze the clinicopathologic features of 10 Chinese prostate adenocarcinoma patients under 50 years. METHODS: Between January 2007 and April 2012, 10 cases of prostate adenocarcinoma patients under 50 years (age: 36-49) were diagnosed at our institution through prostate biopsy. The indications of biopsy were abnormal digital rectal examination (7 cases) and/or a total prostate specific antigen (PSA) over 4.0 µg/L (4 cases). The clinicopathological data of these patients were reviewed. The results of biopsy were 1 case with Gleason score (GS) 6, 4 cases with GS 7 and 5 cases with GS 9. In the study, 7 patients were diagnosed with cT4. Lymph node metastasis and bone metastasis were found in 5 and 4 cases, respectively. The treatments were hormonal therapy in 5 cases, radical prostatectomy in 2 cases and combination therapy in 3 cases. RESULTS: During the follow-up, 6 patients were in progression within 3 to 7 months, 1 patient died after 3 years, and 4 patients were lost of the follow-up. CONCLUSION: These findings suggest that the Chinese prostate adenocarcinoma patients with age under 50 years are likely to have more aggressive tumor and combination therapy might be appropriate.


Assuntos
Adenocarcinoma/cirurgia , Antineoplásicos Hormonais/uso terapêutico , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Adenocarcinoma/patologia , Adulto , Fatores Etários , Biópsia por Agulha , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias da Próstata/patologia
17.
Zhonghua Nan Ke Xue ; 18(2): 155-9, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22568214

RESUMO

OBJECTIVE: To determine the distribution characteristics of cancerous foci in the prostate by retrospective analysis on the radical prostatectomy (RP) samples from patients with prostate cancer diagnosed by single positive core biopsy and treated by RP. METHODS: Thirty-seven patients with prostate cancer diagnosed by ultrasound-guided biopsy and single positive core biopsy underwent RP. We reviewed the pre- and post-operative data of the patients, compared the results of biopsies and pathological examination of the RP samples, and analyzed the factors that led to the underestimation of the overall prostate cancer risks. RESULTS: Post-operative pathological results showed multifocal distribution of the tumors in 70% of the patients (26/37) and obviously increased Gleason score (7-9) in 56% (21/37). The clinical stages of the tumors had been significantly underestimated preoperatively. The underestimation of their clinical stages might be due to a larger proportion of cancer tissues in a single positive core biopsy, and that of the overall cancer risks attributed to PSAD > 0.2 microg/L. Larger prostate volume (> or = 40 ml) increased the possibility of multifocal distribution. CONCLUSION: The risk of prostate cancer diagnosed by single positive core biopsy might be underestimated, and the cancerous foci were characterized by multifocal distribution in the prostate.


Assuntos
Biópsia por Agulha/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
18.
Angew Chem Int Ed Engl ; 51(52): 13070-4, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23161485

RESUMO

Acid brings the oxygen: a general method for palladium-catalyzed C-H oxygenation has been developed for the facile synthesis of a wide range of functionalized phenols with readily available aryl ketones, benzoates, benzamides, acetanilides, and sulfonamides. A trifluoroacetic acid/trifluoroacetic acid anhydride solvent system serves as the oxygen source and is the critical factor for C-H activation.


Assuntos
Anidridos Acéticos/química , Fluoracetatos/química , Compostos Heterocíclicos/química , Oxigênio/química , Paládio/química , Ácido Trifluoracético/química , Carbono/química , Catálise , Cristalografia por Raios X , Hidrogênio/química , Conformação Molecular , Estereoisomerismo
19.
Kaohsiung J Med Sci ; 38(6): 565-573, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35579106

RESUMO

The protective effect of microRNA (miR)-145-5p in acute lung injury (ALI) has been discovered previously. Thus, in this study, we attempted to further investigate the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor ß1 (TGF-ß1)/Smad pathway. A lipopolysaccharide (LPS)-induced ALI rat model was established. The expression of miR-145-5p in ALI rat lung tissues was up-regulated. Afterward, pathological damage in the lung tissue, the wet/dry (W/D) ratio, apoptosis, and serum inflammatory factor contents were observed. miR-145-5p, ETS2, TGF-ß1, Smad2/3, and phosphorylated Smad2/3 levels were measured in rats. miR-145-5p expression was down-regulated, ETS2 expression was up-regulated, and the TGF-ß1/Smad pathway was activated in LPS-exposed rats. Overexpression of miR-145-5p inactivated the TGF-ß1/Smad pathway and attenuated ALI, as reflected by relieved pathological damage, a decreased W/D ratio, reduced apoptosis, and suppressed inflammatory response. In contrast, loss of miR-145-5p or elevated ETS2 levels worsened ALI and activated the TGF-ß1/Smad pathway. Moreover, elevation of ETS2 diminished miR-145-5p-mediated protection against ALI. Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates the TGF-ß1/Smad pathway to ameliorate ALI in rats.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Animais , Lipopolissacarídeos/toxicidade , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Transdução de Sinais/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
20.
Front Pharmacol ; 12: 764282, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899319

RESUMO

Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1ß, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

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