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1.
Nature ; 560(7719): 476-479, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30135526

RESUMO

The early evolution of turtles continues to be a contentious issue in vertebrate palaeontology. Recent reports have suggested that they are diapsids1-6, but the position of turtles within Diapsida is controversial7-12 and the sequence of acquisition of turtle synapomorphies remains unclear1-3. Here we describe a Triassic turtle from China that has a mixture of derived characters and plesiomorphic features. To our knowledge, it represents the earliest known stem turtle with an edentulous beak and a rigid puboischiadic plate. The discovery of this new form reveals a complex early history of turtles.


Assuntos
Bico/anatomia & histologia , Filogenia , Tartarugas/anatomia & histologia , Tartarugas/classificação , Animais , China , Fósseis
2.
Nano Lett ; 22(20): 8076-8085, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36135098

RESUMO

Nanomaterials (NMs) inevitably adsorb proteins in blood and form "protein corona" upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs.


Assuntos
Nanoestruturas , Biblioteca de Peptídeos , Camundongos , Animais , Técnicas de Química Combinatória/métodos , Distribuição Tecidual , Peptídeos/farmacologia , Peptídeos/química , Proteínas Sanguíneas , Administração Intravenosa , Ouro , Portadores de Fármacos
3.
Zhongguo Zhong Yao Za Zhi ; 47(23): 6278-6286, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36604872

RESUMO

Rare and endangered animal medicine, a kind of important Chinese medicine, plays an irreplaceable role in the prevention and treatment of serious acute and chronic diseases and major diseases. Due to resource limitation and depletion and the increasing demand, rare and endangered medicinal animal resources have been drastically reduced or even extinct, which threatens the inheritance of traditional Chinese medicine, the integrity of clinical medicine, and the development of the traditional Chinese medicine industry. For the protection and sustainable utilization of Chinese medicinal resources, artificial substitutes came into being. However, there is still a lack of systematic research on the pharmacological effects and clinical applications of artificial substitutes and whether they can completely replace the original medicinal materials in clinical practice. Therefore, this study focuses on the status quo of rare and endangered animal medicinal materials and their artificial substitutes that have been marketed. To be specific, the two were compared and whether the artificial substitutes can completely replace the original medicinal materials was analyzed. In addition, constructive suggestions on the industrialization of artificial substitutes were put forward, which was expected to promote the sustainable development of Chinese medicinal resources.


Assuntos
Conservação dos Recursos Naturais , Medicamentos de Ervas Chinesas , Animais , Desenvolvimento Industrial , Medicina Tradicional Chinesa , Desenvolvimento Sustentável , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , China
4.
Naturwissenschaften ; 103(11-12): 95, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27830290

RESUMO

Reptiles have a long history of transitioning from terrestrial to semi-aquatic or aquatic environments that stretches back at least 250 million years. Within Archosauria, both living crocodylians and birds have semi-aquatic members. Closer to the root of Archosauria and within the closest relatives of the clade, there is a growing body of evidence that early members of those clades had a semi-aquatic lifestyle. However, the morphological adaptations to a semi-aquatic environment remain equivocal in most cases. Here, we introduce a new Middle Triassic (245-235 Ma) archosauriform, Litorosuchus somnii, gen. et sp. nov., based on a nearly complete skeleton from the Zhuganpo Member (Ladinian [241-235 Ma]) of the Falang Formation, Yunnan, China. Our phylogenetic analyses suggest that Litorosuchus is a stem archosaur closely related to the aberrant Vancleavea just outside of Archosauria. The well-preserved skeleton of L. somnii bears a number of morphological characters consistent with other aquatic-adapted tetrapods including: a dorsally directed external naris, tall neural spines and elongate chevrons in an elongated tail, a short and broad scapula, webbed feet, long cervical vertebrae with long slender ribs, and an elongated rostrum with long and pointed teeth. Together these features represent one of the best-supported cases of a semi-aquatic mode of life for a stem archosaur. Together with Vancleavea campi, the discovery of L. somnii demonstrates a growing body of evidence that there was much more diversity in mode of life outside Archosauria. Furthermore, L. somnii helps interpret other possible character states consistent with a semi-aquatic mode of life for archosauriforms, including archosaurs.


Assuntos
Organismos Aquáticos/classificação , Fósseis , Filogenia , Répteis/anatomia & histologia , Répteis/classificação , Adaptação Fisiológica , Animais , Biodiversidade , China , Especificidade da Espécie
5.
Naturwissenschaften ; 101(3): 251-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24452285

RESUMO

The Luoping fauna (Anisian, Middle Triassic) is probably the oldest of Triassic faunas in Guizhou-Yunnan area, China. The reptilian assemblage is comprised of ichthyosaurs, a number of sauropterygians (pachypleurosaur-like forms), saurosphargids, protorosaurs, and archosauriforms. Here, we report on a peculiar reptile, newly found in this fauna. Its dentition is fence or comb-like and bears more than 175 pleurodont teeth in each ramus of the upper and lower jaws, tooth crown is needle-like distally and blade-shaped proximally; its rostrum strongly bends downward and the anterior end of its mandible expands both dorsally and ventrally to form a shovel-headed structure; and its ungual phalanges are hoof-shaped. The specializations of the jaws and dentition indicate that the reptile may have been adapted to a way of bottom-filter feeding in water. It is obvious that such delicate teeth are not strong enough to catch prey, but were probably used as a barrier to filter microorganisms or benthic invertebrates such as sea worms. These were collected by the specialized jaws, which may have functioned as a shovel or pushdozer (the mandible) and a grasper or scratcher (the rostrum). Our preliminary analysis suggests that the new reptile might be more closely related to the Sauropterygia than to other marine reptiles.


Assuntos
Adaptação Fisiológica/fisiologia , Organismos Aquáticos , Fósseis , Répteis/anatomia & histologia , Répteis/classificação , Animais , China , Dentição , Arcada Osseodentária/anatomia & histologia , Especificidade da Espécie , Dente/anatomia & histologia
6.
Nature ; 456(7221): 497-501, 2008 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-19037315

RESUMO

The origin of the turtle body plan remains one of the great mysteries of reptile evolution. The anatomy of turtles is highly derived, which renders it difficult to establish the relationships of turtles with other groups of reptiles. The oldest known turtle, Proganochelys from the Late Triassic period of Germany, has a fully formed shell and offers no clue as to its origin. Here we describe a new 220-million-year-old turtle from China, somewhat older than Proganochelys, that documents an intermediate step in the evolution of the shell and associated structures. A ventral plastron is fully developed, but the dorsal carapace consists of neural plates only. The dorsal ribs are expanded, and osteoderms are absent. The new species shows that the plastron evolved before the carapace and that the first step of carapace formation is the ossification of the neural plates coupled with a broadening of the ribs. This corresponds to early embryonic stages of carapace formation in extant turtles, and shows that the turtle shell is not derived from a fusion of osteoderms. Phylogenetic analysis places the new species basal to all known turtles, fossil and extant. The marine deposits that yielded the fossils indicate that this primitive turtle inhabited marginal areas of the sea or river deltas.


Assuntos
Fósseis , Esqueleto , Tartarugas/anatomia & histologia , Animais , Evolução Biológica , China , Crânio/anatomia & histologia , Tartarugas/classificação , Tartarugas/fisiologia
7.
Int J Clin Pharmacol Ther ; 52(6): 497-503, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24691060

RESUMO

OBJECTIVE: The purpose of this study was to investigate the associations between CYP3A4*18B and CYP3A5*3 polymorphism and cyclosporine-related liver injuries in Chinese renal transplant recipients. METHODS: We genotyped 339 renal transplant recipients treated with a triple immunosuppressive regimen including cyclosporine for CYP3A4*18B and CYP3A5*3 polymorphism using the polymerase chain reaction restriction fragment length polymorphism assay. RESULTS: The incidence of liver injury in the study population was 36.9% (125/339). At 1 month after transplantation, the trough concentration of cyclosporine (C0) in the group with CYP3A4*1/*1(GG alleles) was significantly higher than in the group with CYP3A4*18B/*1 8B(AA alleles) (p < 0.05). At 3 months after transplantation, the C0 in the group with CYP3A4*1/*1 and group with CYP3A4*1/*18B was markedly higher than in the group with CYP3A4*18B/*18B (p < 0.05). The GG genotypes of CYP3A4*18B were more common in the liver injury group compared with the control group (p < 0.05). Univariate logistic regression analysis showed that subjects carrying the GG genotypes had a 5.136- and 2.528-fold higher risk of developing cyclosporine-related liver injury than those with the AA and GA genotypes. When adjusted for sex, the risk of the CYP3A4*18B genotypes was OR = 4.969 for GG compared to AA (p = 0.030), and OR = 2.634 for GG compared to GA (p = 0.025). However, no association was observed between CYP3A5*3 polymorphisms with cyclosporine-related liver injury. CONCLUSIONS: These results suggested that the wild type of CYP3A4*18B is a risk factor for the development of cyclosporine- related liver injuries in Chinese renal transplant recipients.


Assuntos
Povo Asiático/genética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclosporina/efeitos adversos , Citocromo P-450 CYP3A/genética , Imunossupressores/efeitos adversos , Transplante de Rim , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etnologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Distribuição de Qui-Quadrado , China/epidemiologia , Ciclosporina/sangue , Citocromo P-450 CYP3A/metabolismo , Quimioterapia Combinada , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Imunossupressores/sangue , Incidência , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Fatores de Tempo , Adulto Jovem
8.
Fish Shellfish Immunol ; 34(5): 1131-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23403158

RESUMO

Five feeding trials based on the isonitrogenous and isoenergetic experimental diets containing 34% protein, 6%, 8%, 10%, 12% or 14% lipid respectively in the circulating water culture system for both 30 and 60 days were conducted to investigate the effect of the dietary lipid level on the growth and immunity in white shirmp, Litopenaeus vannamei adults. The body weight and specific growth rate of white shrimp in different treatments indicated that shrimps fed the diet of 12% lipid level for 30d and 10% lipid level for 60d had the best developmental status. The ability of respiratory burst in hemocytes was improved as the increase of dietary lipid level. The transcripts of LGBP and pPO were sensitive to the dietary lipid in hemocyte and hepatopancreas respectively. The activities of CAT, GPx and AKP were increased to a certain extend according to dietary lipid level. Qualification of MDA showed the lowest level in the sample subjected to 12% lipid level diet, indicating an optimal utilization of the dietary lipid and an efficient clearance of MDA in vivo. These results suggested that dietary lipid level of 10-12% significantly tunes the growth and enhance the immune abilities mainly via ROS pathway of L. vannamei.


Assuntos
Aquicultura , Lipídeos/administração & dosagem , Penaeidae/fisiologia , Ração Animal , Animais , Dieta/veterinária , Regulação da Expressão Gênica , Hemócitos/citologia , Imunidade Inata , Longevidade , Malondialdeído/metabolismo , Penaeidae/genética , Penaeidae/crescimento & desenvolvimento , Penaeidae/imunologia , Reação em Cadeia da Polimerase/veterinária , Explosão Respiratória
9.
Sci Rep ; 13(1): 11221, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464026

RESUMO

Dinosaurs and mammals have coexisted for the last ~ 230 million years. Both groups arose during the Late Triassic and diversified throughout the Mesozoic and into the Cenozoic (the latter in the form of birds). Although they undoubtedly interacted in many ways, direct fossil evidence for their interaction is rare. Here we report a new fossil find from the Lujiatun Member of the Lower Cretaceous Yixian Formation of China, showing a gobiconodontid mammal and psittacosaurid dinosaur locked in mortal combat. We entertain various hypothesized explanations for this association, but the balance of the evidence suggests that it represents a predation attempt on the part of the smaller mammal, suddenly interrupted by, and preserved within, a lahar-type volcanic debris flow. Mesozoic mammals are usually depicted as having lived in the shadows of their larger dinosaurian contemporaries, but this new fossil convincingly demonstrates that mammals could pose a threat even to near fully-grown dinosaurs. The Yixian Formation-and the Chinese fossil Jehol Biota more broadly-have played a particularly important role in revealing the diversity of small-bodied dinosaurs and other fauna. We anticipate that the volcanically derived obrution deposits specific to the Lujiatun Member will likewise continue to yield evidence for biotic interactions otherwise unknown from the rest of the fossil record.


Assuntos
Dinossauros , Fósseis , Animais , Dinossauros/anatomia & histologia , Aves , Mamíferos , Comportamento Predatório , Evolução Biológica , Filogenia
10.
Chin J Traumatol ; 15(3): 131-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22663905

RESUMO

OBJECTIVE: To study the adherence, proliferation and osteogenesis of mesenchymal stem cells (MSCs) cultured on different HA/ZrO2 composites. METHODS: The simplex and graded HA/ZrO2 compo-sites were prepared using dry-laid method. The surface topography of the composites was observed by scanning electron microscope (SEM). The MSCs were isolated from rabbits and cultured on experimental groups (simplex HA/ZrO2 composite, graded HA/ZrO2 composite, pure HA or pure ZrO2 coatings respectively) and control group (ordinary culture plate). Then, we observed the adherence, proliferation and osteogenesis of the MSCs, detected the cellular alkaline phosphatase (ALP) activities, extracted total RNA and detected the mRNA expression of collagen I, osteocalcin and osteopontin using the reverse transcription and polymerase chain reaction (RT-PCR) method. RESULTS: The SEM images confirmed that the surface of the simplex HA/ZrO2 composite was coverd by discon-tiguous HA layer with clear visualization of the partial ZrO2 matrix, while the surface of the graded HA/ZrO2 composite was fairly rough with porosity. X-ray diffraction showed that after high temperature sintering, the ZrO2 phase still remained, while the HA phase was transformed to beta-Ca3(PO4)2 , alpha-Ca3(PO4)2 and CaZrO3 phases on the surface of both composites. Cell culture indicated that the HA/ZrO2 composites supported cell attachment. Neither ALP expression nor mRNA expression of collagen I, osteocalcin or osteopontin from RT-PCR results showed significant deviation among four groups. CONCLUSION: Among these four composites, the graded HA/ZrO2 composite promotes the MSCs proliferation and the osteogenic differentiation to a certain extent.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Diferenciação Celular , Células Cultivadas , Durapatita , Células-Tronco Mesenquimais/citologia , Osteocalcina
11.
iScience ; 25(12): 105635, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36483013

RESUMO

Sauropterygia is the most diversified and dominant clade among marine reptiles, but their early evolution is scarcely understood. Here we report the earliest known complete specimen related to sauropterygians from the Early Triassic. It is referred to Hanosaurus hupehensis by an exclusive combination of features and shows mosaic morphology integrating the characters of multiple sauropterygian sub-lineages. In phylogenetic results from both parsimony and Bayesian analyses employing our reconstructed dataset, Hanosaurus is stably resolved as the basal-most member of Sauropterygiformes, a clade comprising all sauropterygians and saurosphargids. This skeleton reveals an unexpected ancestral body plan for sauropterygiforms with an elongate trunk and four short limbs, differing from many of its immediate descendants but more similar to non-sauropterygiform marine reptiles at their early aquatic stage as axial swimmers. After this convergence on body plan, we quantitatively confirm the rapid divergence of sauropterygiform reptiles following the end-Permian mass extinction.

12.
Naturwissenschaften ; 97(4): 423-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20179895

RESUMO

Viviparity (giving birth to live young) in fossil reptiles has been known only in a few marine groups: ichthyosaurs, pachypleurosaurs, and mosasaurs. Here, we report a pregnant specimen of the Early Cretaceous Hyphalosaurus baitaigouensis, a species of Choristodera, a diapsid group known from unequivocal fossil remains from the Middle Jurassic to the early Miocene (about 165 to 20 million years ago). This specimen provides the first evidence of viviparity in choristoderan reptiles and is also the sole record of viviparity in fossil reptiles which lived in freshwater ecosystems. This exquisitely preserved specimen contains up to 18 embryos arranged in pairs. Size comparison with small free-living individuals and the straight posture of the posterior-most pair suggest that those embryos were at term and had probably reached parturition. The posterior-most embryo on the left side has the head positioned toward the rear, contrary to normal position, suggesting a complication that may have contributed to the mother's death. Viviparity would certainly have freed species of Hyphalosaurus from the need to return to land to deposit eggs; taking this advantage, they would have avoided intense competition with contemporaneous terrestrial carnivores such as dinosaurs.


Assuntos
Osso e Ossos/anatomia & histologia , Fósseis , Répteis/fisiologia , Viviparidade não Mamífera , Animais , Embrião não Mamífero/anatomia & histologia , Feminino , Palato/anatomia & histologia , Crânio/anatomia & histologia
13.
Nature ; 432(7015): 383-6, 2004 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-15549103

RESUMO

Sauropterygians form the largest and most diverse group of ancient marine reptiles that lived throughout nearly the entire Mesozoic era (from 250 to 65 million years ago). Although thousands of specimens of this group have been collected around the world since the description of the first plesiosaur in 1821 (ref. 3), no direct evidence has been found to determine whether any sauropterygians came on shore to lay eggs (oviparity) like sea turtles, or gave birth in the water to live young (viviparity) as ichthyosaurs and mosasauroids (marine lizards) did. Viviparity has been proposed for plesiosaur, pachypleurosaur and nothosaur sauropterygians, but until now no concrete evidence has been advanced. Here we report two gravid specimens of Keichousaurus hui Young from the Middle Triassic of China. These exquisitely preserved specimens not only provide the first unequivocal evidence of reproductive mode and sexual dimorphism in sauropterygians, but also indicate that viviparity could have been expedited by the evolution of a movable pelvis in pachypleurosaurs. By extension, this has implications for the reproductive pattern of other sauropterygians and Mesozoic marine reptiles that possessed a movable pelvis.


Assuntos
Parto/fisiologia , Répteis/anatomia & histologia , Répteis/fisiologia , Animais , Evolução Biológica , China , Feminino , Fósseis , História Antiga , Masculino , Biologia Marinha , Esqueleto , Fatores de Tempo
14.
Br J Clin Pharmacol ; 67(5): 541-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19552749

RESUMO

AIMS: To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of midazolam, a probe drug of CYP3A, and its metabolite 1'-hydroxy midazolam in healthy volunteers. METHODS: Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 7 days. Pharmacokinetic investigations of oral midazolam administration at 15 mg were performed both before and at the end of the SchE treatment period. The plasma midazolam and 1'-hydroxy midazolam concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques. RESULTS: Following administration of SchE, the average increases (%) of individual increases in AUC, AUMC and C(max) of midazolam were 119.4% [95% confidence interval (CI) 83.9, 155.0], 183.4% (95% CI 120.5, 246.2) and 85.6% (95% CI 14.4, 156.9), respectively (P < 0.01 or 0.05). On average, there was a 133.3% (95% CI 8.9, 257.7) increase in midazolam t(max) (P < 0.01). The average decrease (%) in CL/F was 52.1% (95% CI 44.9, 59.4) (P < 0.01). No significant changes were seen in midazolam half-life. After co-administration of SchE, the average increase (%) in t(max) of 1'-hydroxy midazolam was 150.0% (95% CI 22.2, 277.8) (P < 0.05). No significant differences were observed in the other pharmacokinetic parameters of 1'-hydroxy midazolam. CONCLUSIONS: SchE can markedly increase the oral bioavailability of midazolam in healthy volunteers. SchE is an inhibitor of CYP3A and has a high susceptibility to alter the disposition of drugs metabolized by CYP3A.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Midazolam/farmacocinética , Extratos Vegetais/farmacologia , Schisandra/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Interações Medicamentosas , Meia-Vida , Humanos , Masculino , Midazolam/administração & dosagem , Midazolam/sangue , Pessoa de Meia-Idade , Adulto Jovem
15.
Eur J Clin Pharmacol ; 65(3): 249-55, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19048245

RESUMO

OBJECTIVE: To systematically investigate the relationships between thiopurine S-methyltransferase (TPMT) polymorphisms and azathioprine-related adverse drug reactions in patients with kidney transplantation. METHODS: Erythrocyte TPMT activity of 150 patients with kidney transplantation and AZA therapy was determined by HPLC. The frequency of four common TPMT mutant alleles, TPMT*2, *3A, *3B, and *3C was determined by allele-specific PCR and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Thirty cases (20%) had stopped azathioprine medication or were on reduced dose due to azathioprine-related side effects. The TPMT activity range of cases who never experienced side effects was 16.63-68.25 U, the mean of the controls was 38.43 +/- 11.59 U. The mean value of 12 cases with hematotoxicity was 23.50 +/- 10.33 U, much lower than the control mean (P < 0.05). No significant difference between the mean value of 18 cases with hepatotoxicity and the control mean (P > 0.05) was seen. No case with TPMT deficiency was found in all patients studied, and TPMT*2, *3A, and *3B were not detected in any of them. TPMT*3C heterozygous alleles were found in 4.7% (seven cases) of these patients, all seven cases had intermediate TPMT activity, and the mean was 16.75 +/- 2.09 U, much lower than other TPMT wild-type patients (P < 0.05). In the seven TPMT*3C patients, four cases experienced side effects (hematotoxicity, n = 2; hepatotoxicity, n = 2). CONCLUSIONS: This study demonstrates that TPMT activity is reduced in patients with TPMT*3C mutation. AZA-induced hematotoxicity is related to the reduced TPMT activity.


Assuntos
Azatioprina/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Rim , Metiltransferases/genética , Adulto , Idoso , Povo Asiático , Azatioprina/administração & dosagem , Azatioprina/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Feminino , Frequência do Gene , Rejeição de Enxerto/prevenção & controle , Doenças Hematológicas/induzido quimicamente , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético
16.
Arch Pharm (Weinheim) ; 342(9): 513-20, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19598290

RESUMO

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.


Assuntos
Antineoplásicos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Fígado/efeitos dos fármacos , Pró-Fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Ácido Cólico/química , Ácido Cólico/farmacocinética , Feminino , Fluoruracila/química , Fluoruracila/farmacocinética , Camundongos , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Distribuição Tecidual
17.
Clin Chim Acta ; 387(1-2): 128-32, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18028892

RESUMO

BACKGROUND: There is an increase prevalence of chronic kidney disease (CKD)worldwide. However, the exact incidence of CKD in China is still uncertain. In this cross-sectional study, we retrospectively investigated the prevalence and distribution of CKD in Chinese hospitalised adult patients. METHODS: Totally, 13,383 adults patients who were hospitalised at our hospital were included in this study. They included 6215 males and 7168 females. Patients' gender, age, blood pressure, serum creatinine, blood urea nitrogen, uric acid, triglyceride, total cholesterol, albumin, hemoglobin, hemotocrit, urine protein, and history of hypertension, diabetes, and smoking were investigated. CKD was defined as eGFR<60 ML/ MIN PER 1.73 m(2) and/or proteinuria, GFR was estimated by using of the simplified MDRD equation. RESULTS: The prevalence rate of CKD was 14.82% in our group, which was respectively distributed from 1 to stage 5 at the following percentage, 3.33% (stage 1), 2.49% ( stage 2), 7.07% (stage 3), 1.08% (stage 4), and 0.86% (stage 5). Elderly patients (age >65 y) accounted for 53.07%, which had a higher CKD prevalence (29.47%) than middle and young-aged patients (9.49%). It was noted that 39.06% patients at stage 1-3 were undiagnosed with CKD during their hospitalization. The common etiology for CKD was hypertension (29.49%), diabetes (11.64%) and primary glomerulonephritis (4.39%). Hypertension, diabetes and ages were main associated factors for CKD. CONCLUSIONS: CKD is a very common disease among the hospitalised patients in China. With the increasing of aging population, elderly people will be the highest risk group for CKD. More strategies have to be made for its early detection and prevention.


Assuntos
Hospitalização , Pacientes Internados , Falência Renal Crônica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
18.
Biomaterials ; 156: 248-257, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29216535

RESUMO

The blockade of PD-1/PD-L1 interaction by peptide antagonists can unleash and enhance pre-existing anti-cancer immune responses of T cells to eradicate cancer cells. However, low proteolytic stability is the "Achilles' Heel" of peptides. Here, we first report a nanoantagonist with a physiological temperature sensitive nanophase-segregated surface that exhibits significantly enhanced blood circulation, peptide stability and PD-L1 immune checkpoint blockade efficacy. Thermosensitive polymers with different phase transition temperatures (Tt) are used to form the nanophase-segregated surface on an Au nanorod core. Importantly, the nanophase-segregated surface aids the nanoantagonist to resist protein adsorption and enhance the systemic stability of the linked peptides. Finally, the as-designed nanoantagonist effectively blocks PD-1/PD-L1 interaction in vitro and in vivo, enhances the pre-existing CD8+ T cell tumor destruction capability and inhibits tumor growth. This study offers a new strategy for designing nano-formulations for cancer immunotherapy.


Assuntos
Imunoterapia , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/terapia , Adsorção , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antígeno B7-H1/metabolismo , Circulação Sanguínea/efeitos dos fármacos , Feminino , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Peptídeos/química , Polímeros/síntese química , Polímeros/química , Receptor de Morte Celular Programada 1/metabolismo , Ligação Proteica , Propriedades de Superfície , Temperatura , Distribuição Tecidual/efeitos dos fármacos
19.
Zhonghua Yi Xue Za Zhi ; 87(38): 2672-6, 2007 Oct 16.
Artigo em Zh | MEDLINE | ID: mdl-18167241

RESUMO

OBJECTIVE: To retrospectively investigate the prevalence and distribution of chronic kidney disease (CKD) in hospitalized Chinese adult patients. METHODS: The medical histories of 13,383 adult patients hospitalized in Zhongda Hospital from September 2004 to August 2005, 6215 males and 7168 female, aged (51 +/- 19) (18 - 103), were reviewed. The blood pressure, serum creatinine, proteinuria were investigated. CKD was defined and classified according to the NKF/DOQI guideline. Glomerular filtration rate (GFR) was estimated by using the simplified modification of diet in renal disease study (MDRD) equation. eGFR = 186.3 x serum creatinine(-1.154) x age(-0.203) x (0.742 for women) ml.min(-1).(1.7 3 m2)(-1). RESULTS: The prevalence rate of CKD was 14.82% in this group, and the prevalence rates of CKD of stage 1 to 5 were 3.33%, 2.49%, 7.07%, 1.08%, and 0.86% respectively. 53.07% of the CKD patients were elderly patients (age > 65) with a CKD prevalence rate of 29.47%, significantly higher than that of the middle-aged and young patients (9.49%, P < 0.01). The eGFR levels of 9.01% of the hospitalized patients were below 60 ml.min(-1).(1.73 m2)(-1). The prevalence rate of proteinuria was 8.87%. 39.06% of the patients at stages 1 - 3 failed to be diagnosed as with CKD during their hospitalization. The most common causes of CKD were hypertension (29.49%), diabetes (11.64%), and primary glomerulonephritis (4.39%). Hypertension, diabetes and being elderly were main risk factors for CKD. CONCLUSION: CKD is a very common disease among the hospitalized patients in China. With the increasing number of aging populations, elderly people will be the highest risk group for CKD. More strategies have to be made for its early detection and prevention.


Assuntos
Hospitalização/estatística & dados numéricos , Nefropatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Doença Crônica , Complicações do Diabetes , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite/complicações , Humanos , Hipertensão/complicações , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(1): 174-8, 2007 Feb.
Artigo em Zh | MEDLINE | ID: mdl-17344613

RESUMO

OBJECTIVE: To evaluate the clinical and pathological features of 94 children suffering from IgA nephropathy (IgAN) while estimating the prevalent situation in Hunan province. METHODS: To summarize the annual number of hospitalized children, those with kidney diseases, those accepted biopsy, and those confirmed as IgAN in both Xiangya Hospital and Second Xiangya Hospital undertaking kidney biopsy in Hunan province during 1995 and 2004. RESULTS: In the past 10 years, as the hospitalized population in both hospitals accrued to 9.98% each year. The rate of 7.5% was seen in those with kidney diseases. Among whom 56.3% accepted kidney biopsy and 94 of them were confirmed as IgAN. Hematuria was the main clinical presentation, seen in 71 cases, accounting to 76%, and even to 98% after excluding those with nephrotic syndrome and isolating proteinuria type of IgAN. Inflammation infiltration (91%), renal tubule degeneration (81%), and renal interstitial fibrosis (31%) were the major pathological features of 94 children, especially in nephrotic syndrome IgAN. CONCLUSION: The number of children with IgAN synchronously accrues as hospitalized population, those with kidney diseases, and those by kidney biopsy. Hematuria is the major symptom. To routinely perform urine analysis and kidney biopsy in asymptomatic hematuria may improve the diagnosis. Inflammation infiltration, renal tubule degeneration, and renal interstitial fibrosis are the major pathological features in IgAN children, especially in nephrotic syndrome IgAN, probably relating to continuous proteinuria. Early control of proteinuria may delay or decrease renal tubule fibrosis.


Assuntos
Glomerulonefrite por IGA/patologia , Rim/patologia , Adolescente , Biópsia por Agulha , Criança , Pré-Escolar , China/epidemiologia , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/epidemiologia , Hematúria/diagnóstico , Hematúria/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino
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