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1.
Mol Psychiatry ; 29(5): 1253-1264, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38228891

RESUMEN

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.


Asunto(s)
Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Proteínas de la Membrana , Trastornos del Neurodesarrollo , Animales , Ratones , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Masculino , Neuronas/metabolismo , Conducta Animal/fisiología , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Ratones Noqueados , Trastorno Autístico/genética , Trastorno Autístico/metabolismo , Ratones Endogámicos C57BL , Conducta Social , Conducta Estereotipada , Sinapsis/metabolismo , Femenino
2.
Angew Chem Int Ed Engl ; : e202405382, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682252

RESUMEN

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm=204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

3.
EMBO J ; 37(20)2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30181118

RESUMEN

The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs in vitro Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Osteogénesis , Transducción de Señal , Proteasas Ubiquitina-Específicas/metabolismo , Animales , Proteína Morfogenética Ósea 2/genética , Regeneración Ósea/genética , Técnicas de Silenciamiento del Gen , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Noqueados , Osteoblastos/citología , Osteoblastos/metabolismo , Proteasas Ubiquitina-Específicas/genética
4.
Anal Bioanal Chem ; 412(28): 7891-7897, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32888045

RESUMEN

Metabolites have a close relationship with the efficacy and safety of herbal medicines. However, ubiquitous matrix interferences, complex co-elution, and minor or trace amounts in plasma restrict the comprehensive identification of metabolites. In this study, an efficient strategy comprising a mass defect filter and time-staggered targeted ion lists was established to characterize the metabolites of alkaloids of Uncaria rhynchophylla (UR) for the systematic comparison of metabolic differences in rat, mouse, dog, pig, monkey and human liver microsomes. The mass defect filter model effectively decreased interfering ions by 63-68%, and time-staggered precursor ion lists significantly increased the number of triggered MS/MS fragmentation by 65-120% in liver microsomes of six species. Ultimately, a total of 165 metabolites in the liver microsomes of six species were tentatively characterized, and the main metabolic pathways were demethylation, isomerization, hydrolysis, oxygenation and dehydrogenation. The results showed that the mouse liver microsomes exhibited metabolic behavior most similar to human metabolism of UR alkaloids. We hope that these results provide basic data for further investigation of UR metabolism in different species, and that the strategy can provide a reference for metabolite characterization of herbal medicines in complex biological matrix. Graphical abstract.


Asunto(s)
Microsomas Hepáticos/metabolismo , Uncaria/metabolismo , Animales , Cromatografía Líquida de Alta Presión/métodos , Perros , Haplorrinos , Humanos , Ratones , Ratas , Especificidad de la Especie , Espectrometría de Masa por Ionización de Electrospray/métodos , Porcinos , Espectrometría de Masas en Tándem/métodos
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 781-785, 2018 Sep.
Artículo en Zh | MEDLINE | ID: mdl-30378344

RESUMEN

OBJECTIVE: To determine the effects of guided bone regeneration (GBR) and delayed loading on autogenous bone ring grafting. METHODS: Autogenous bone ring augmentation with simultaneous implant insertion was performed in the mandibular premolars region of six Beagle dogs. The Bone quality of four mandibular premolars [second premolar (P2) and fourth premolar (P4)] were detected using cone beam CT (CBCT). The P2s and P4s of bilateral mandible were extracted, with three extracting sites being randomly selected to create buccal defects and the remaining one serving as control. GBR and bone ring grafting with simultaneous implant insertion was performed on two of the three experimental sites with buccal defects 3 months later, while the other one was treated with bone ring grafting with simultaneous implant insertion. Routine implant placement was performed in the control group. Vertical bone resorption and sulcus deep around the implants were measured three months after occlusal loading with abutment. RESULTS: Three months after operations, 83.3% of bone rings grafts were successful and 100% of implants survived. Delayed healing appeared more in the dogs with GBR compared those treated with bone ring grafting with simultaneous implant insertion, resulting in an increase in vertical bone resorption. Compared with the control group, delayed loading had no effects on vertical bone resorption and the health of gingiva tissues after autogenous bone ring transplant. CONCLUSION: GBR is not a preferred procedure for bone ring grafts, which may increase the risk of delayed healing and site infections, leading to failure of implants. Healed bone ring grafts can resist loadings as normal.


Asunto(s)
Regeneración Ósea , Trasplante Óseo , Implantación Dental Endoósea , Animales , Diente Premolar , Perros , Encía , Mandíbula
7.
Antioxidants (Basel) ; 13(6)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38929189

RESUMEN

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity. A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity. A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors.

8.
JAMA Netw Open ; 7(5): e2413708, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38809553

RESUMEN

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.


Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , China/epidemiología , Estudio de Asociación del Genoma Completo , Estudios de Casos y Controles , Adulto , Factores de Riesgo , Suplementos Dietéticos , Estudios de Cohortes , Anciano , Antibacterianos/uso terapéutico
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 291-6, 2013 Apr 18.
Artículo en Zh | MEDLINE | ID: mdl-23591354

RESUMEN

OBJECTIVE: To study the influence of HPMC as hydrophilic matrix materials and controlled-layer components on the drug release of sustained-release matrix tablets and bilayer tablets. METHODS: Diltiazem hydrochloride was chosen as the water-soluble model drug to prepare different kinds of matrix tablets and double layer tablets with different formulations, and evaluate how the levels and grades of HPMC affect the drug release in sustained-release tablets and bilayer tablets. RESULTS: HPMC with high viscosity and the amount of 20%-40% could delay the drug release to certain degree, but it was difficult to further slow down the drug release up to 24 h, especially for a water soluble drug. Combining HPMC with 5%-20% of CMC-Na was proven to be an effective way to achieve the 24 h release profile with the water soluble drug. HPMC was also investigated as a component in the double layer tablet as base layer. Drug release was complicated compared with EC as the base layer in the double layer tablet due to the great swelling ability of HPMC. HPMC's larger swilling let it form a big cap to retard the drug release, which could significantly affect the drug release with a large ratio of the base layer to the drug layer; furthermore increasing the quality of 10%-40% of the base layer and the proportion of HPMC could reduce the initial burst release. CONCLUSION: The grade/level of HPMC and combinations with other matrix materials had a big impact on the drug release. HPMC could be used in the base layer of the double tablet to alternate the drug release profile, and reduce the initial burst release of the double-layer matrix tablet, and potentially change the drug mechanism.


Asunto(s)
Preparaciones de Acción Retardada/química , Metilcelulosa/análogos & derivados , Metilcelulosa/química , Composición de Medicamentos , Lactosa/análogos & derivados , Lactosa/química , Propranolol/química , Comprimidos/química , Tecnología Farmacéutica/métodos
10.
World J Clin Cases ; 11(12): 2803-2810, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37214575

RESUMEN

BACKGROUND: Postoperative complications of triceps surae intramuscular hemangioma surgery with talipes equinovarus have rarely been described, and the evidence for treatment is limited. The purpose of this case study was to report the new application of the Ilizarov technique, which successfully treated talipes equinovarus in adults after triceps surae intramuscular hemangioma. CASE SUMMARY: A 29-year-old woman treated with the Ilizarov technique for talipes equinovarus in the right leg after triceps surae intramuscular hemangioma surgery. The equinus deformity was roughly corrected after 2 years of follow-up, without significant secondary sequelae. CONCLUSION: Talipes equinovarus caused by postoperative sequelae of intramuscular hemangioma was successfully corrected by the Ilizarov technique. The Ilizarov technique may be used for treating talipes equinovarus caused by various causes.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 121987, 2023 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-36265304

RESUMEN

A qualitative analysis of melamine-adulterated milk was proposed based on two-trace two-dimensional (2T2D) auto-correlation spectra. The concentration of melamine was used as external perturbation, and 40 adulterated samples of each brand with different concentrations of melamine (0.01 g/L to 1 g/L) were configured. Four brands of milk were used to configure experimental samples, including Guangming brand, Mengniu brand, Sanyuan brand and Wandashan brand. Spectroscopic data of pure milk and melamine-adulterated milk were measured by infrared (IR) (80-4000 cm-1) spectrophotometer. 2T2D auto-correlation spectral technology combined with least squares support vector machine (LS-SVM) method was used for qualitative analysis. The two strongest auto-correlation peaks in the auto-correlation spectra were selected for modeling. For Guangming brand, the intensities of auto-correlation at two wave numbers 2898 cm-1 and 2972 cm-1 were selected as independent variables. For Mengniu brand, the intensities of auto-correlation at two wave numbers 2852 cm-1 and 2920 cm-1 were selected. For Sanyuan brand, the intensities of auto-correlation at two wave numbers 2900 cm-1 and 2974 cm-1 were selected. For Wandashan brand, the intensities of auto-correlation at two wave numbers 2900 cm-1 and 2974 cm-1 were selected. For four brands fused together, the intensities of auto-correlation at two wave numbers 2900 cm-1 and 2974 cm-1 were selected. For each brand, the accuracy of qualitative analysis was 100 %. For four brands fused together, the accuracy of qualitative analysis was 99.05 %. In this way, it greatly reduced the amount of data to be processed. This study showed that 2T2D auto-correlation spectral technology combined with LS-SVM method was perfect for the discrimination of melamine-adulterated milk.


Asunto(s)
Contaminación de Alimentos , Leche , Animales , Leche/química , Contaminación de Alimentos/análisis , Espectroscopía Infrarroja Corta , Análisis de los Mínimos Cuadrados , Máquina de Vectores de Soporte
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(5): 742-8, 2012 Oct 18.
Artículo en Zh | MEDLINE | ID: mdl-23073585

RESUMEN

OBJECTIVE: To study the release profiles of Ambroxol hydrochloride in matrix tablets with different fillers and controlled release materials, and investigate the potential impact on different fillers on the matrix tablet's scale-up. METHODS: Ambroxol hydrochloride was chosen as the model drug to make single-layer matrix tablets with different types of hydroxylpropyl methylcellulose as matrix material, and lactose or microcrystalline cellulose as the filler. In vitro dissolution test was used to evaluate the drug release performance of the matrix tablets made. Also ethyl cellulose was used to prepare double-layer matrix tablets to investigate how different kinds of hydroxypropyl methylcellulose (HPMC) and fillers would affect the drug release in double-layer matrix tablets. RESULTS: The drug release rate of single-layer tablets with lactose and HPMC decreased significantly with the increase of the level and viscosity of HPMC. However the release profile only slightly slowed down with the increase of the content and viscosity of HPMC for single-layer matrix tablets of microcrystalline cellulose (MCC). Compared with the single-layer tablets, the level and viscosity of HPMC had less impact on the drug release of the double-layer matrix tablets. CONCLUSION: The matrix tablet with lactose and HPMC has greater flexibility to design formulations with different drug release rate, however the introduction of other process parameters during the scale-up could lead the shifting of the drug release profile from small scale batches. The drug release profiles of matrix tablets with insoluble filler-MCC only change within a small range with the increase of the level and viscosity of HPMC. From the formulation design point of view, it could be necessary to select different type of controlled release polymers to meet the design requirement.


Asunto(s)
Ambroxol/administración & dosificación , Preparaciones de Acción Retardada/química , Portadores de Fármacos , Expectorantes/administración & dosificación , Química Farmacéutica , Excipientes/química , Lactosa/química , Metilcelulosa/análogos & derivados , Metilcelulosa/química , Comprimidos
13.
Sci Total Environ ; 802: 149891, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34474296

RESUMEN

Animals exposure to polychlorinated biphenyls (PCBs) may result in retention of hydroxylated PCBs (OH-PCBs). OH-PCBs can be accumulated in animals, including humans, through the transmission of food chain. However, there are few studies on the accumulation and metabolism of OH-PCBs exposed to the body through daily diet. Therefore, this study was conducted to investigate the fate of OH-PCBs after being ingested through dietary intake. By adding 3-OH-PCB101 and 4-OH-PCB101 to the edible tissue of crucian carp, which were used as raw materials to prepare mouse feed, with an exposure concentration of 2.5 µg/kg ww. The exposure experiment lasted for a total of 80 days. The blood, feces and 11 tissues of mice at different times were analyzed qualitatively and quantitatively. It was found that major OH-PCB101 were accumulated in intestine or excreted with feces. A small part was accumulated in heart, lung and spleen. For the first time that the conversion from OH-PCB101 to PCB101 in mice was discovered, which shows from another perspective that persistent organic pollutants are difficult to be completely degraded in the environment. 4-MeO-PCB101, 3-MeSO2-PCB101, and 4-MeSO2-PCB101 were also found in various tissues. The results of this study show that after OH-PCBs accumulated in animals re-enter the organism through the food chain, they can be metabolized again and may be reversely transformed into the parent compounds. The present research shed new light on simulating the metabolic transformation process of OH-PCBs exposed to mammals through ingestion of fish. Available data show that second-generation persistent organic pollutants in the environment still need to be continuously concerned.


Asunto(s)
Contaminantes Ambientales , Bifenilos Policlorados , Animales , Dieta , Peces , Hidroxilación , Ratones , Bifenilos Policlorados/análisis
14.
Environ Pollut ; 307: 119583, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35680065

RESUMEN

Polychlorinated biphenyls (PCBs) have been attracting global concern due to their persistence and toxicity. However, the study on the metabolites of PCBs in freshwater fish is limited. In this study, the metabolites of 2,2',4,5,5'-Pentachlorobiphenyl (PCB101) in silver crucian carp (Carassius auratus gibelio) were identified for the first time. After intraperitoneal injection of PCB101 (2 mg/kg), the results showed that it could be metabolized to at least three types of metabolites, including hydroxylated (OH-), methoxylated (MeO-) and methyl sulfonated (MeSO2-) PCB101. The OH- metabolites identified in most tissues were 3-OH-PCB101and 4-OH-PCB101, such as liver, gallbladder, blood and muscle. MeSO2- metabolites identified in gallbladder, blood and brain were 3-MeSO2-PCB101 and 4-MeSO2-PCB101. Meanwhile, the MeO- metabolite identified in liver, gallbladder, blood and spleen of silver crucian carp was 4-MeO-PCB101. The investigation of the types and structures of PCB101 and its metabolites, as well as the tissue distribution and accumulation characteristics in silver crucian carp are beneficial to understand the transformation and metabolic mechanisms of PCBs in aquatic organisms. It is of great significance to identify potential pollution hazards of precursor compounds and their metabolites on aquatic products and ensure the quality and safety of aquatic products.


Asunto(s)
Carpas , Bifenilos Policlorados , Animales , Carpas/metabolismo , Carpa Dorada , Bifenilos Policlorados/metabolismo
15.
Front Oncol ; 11: 682021, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34211850

RESUMEN

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive cancer with poor prognosis. The lack of effective targeted therapies for TNBC remains a profound clinical challenge. Fusion transcripts play critical roles in carcinogenesis and serve as valuable diagnostic and therapeutic targets in cancer. The present study aimed to identify novel fusion transcripts in TNBC. METHODS: We analyzed the RNA sequencing data of 360 TNBC samples to identify and filter fusion candidates through SOAPfuse and ChimeraScan analysis. The characteristics, including recurrence, fusion type, chromosomal localization, TNBC subgroup distribution, and clinicopathological correlations, were analyzed in all candidates. Furthermore, we selected the promising fusion transcript and predicted its fusion type and protein coding capacity. RESULTS: Using the RNA sequencing data, we identified 189 fusion transcripts in TNBC, among which 22 were recurrent fusions. Compared to para-tumor tissues, TNBC tumor tissues accumulated more fusion events, especially in high-grade tumors. Interestingly, these events were enriched at specific chromosomal loci, and the distribution pattern varied in different TNBC subtypes. The vast majority of fusion partners were discovered on chromosomes 1p, 11q, 19p, and 19q. Besides, fusion events mainly clustered on chromosome 11 in the immunomodulatory subtype and chromosome 19 in the luminal androgen receptor subtype of TNBC. Considering the tumor specificity and frameshift mutation, we selected MFGE8-HAPLN3 as a novel biomarker and further validated it in TNBC samples using PCR and Sanger sequencing. Further, we successfully identified three types of MFGE8-HAPLN3 (E6-E2, E5-E3, and E6-E3) and predicted the ORF of E6-E2, which could encode a protein of 712 amino acids, suggesting its critical role in TNBC. CONCLUSIONS: Improved bioinformatic stratification and comprehensive analysis identified the fusion transcript MFGE8-HAPLN3 as a novel biomarker with promising clinical application in the future.

16.
Eur J Pharmacol ; 821: 1-10, 2018 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-29247613

RESUMEN

Lariciresinol (LA) is one of the main active ingredients in many traditional medicinal plants such as Patrinia, and has the role of anti-liver cancer. However, the precise mechanisms are unclear. This study investigated the molecular mechanisms of LA against HepG2 cells. LA anti-tumor activity was assessed with the CCK-8, Ki-67, and immunofluorescence staining. Cells apoptotic ratio was evaluated by Annexin V/PI double-staining assay. A proteomic approach was used to identify differentially expressed proteins after LA treatment. JC-1 staining was carried out to detect the mitochondrial membrane potential (ΔΨm), and the Western blot analysis was used to analyse the apoptosis-associated proteins. Our results suggested that LA significantly suppressed the viability of HepG2 cells. The CCK-8 and Ki-67 expression indicated dose-dependent decreases in cell proliferation. Flow cytometry analysis showed that LA exhibited a apoptosis-inducing effect. The proteomic study observed the presence of apoptosis-associated proteins and mitochondrial dysfunction in HepG2 cells after LA-treatment. Further analysis showed that LA could trigger the mitochondrial-mediated apoptosis pathway, based on a decrease in ΔΨm; deliver of cytochrome c; activation of caspase-9/-3 and poly(ADP-ribose) polymerase; and decrease of the proportion of Bcl-2/Bax. Collectively, our studies found that LA exhibits significant cytotoxic effects by inhibiting cell proliferation, inducing apoptosis, possibly via activation of the mitochondrial-mediated apoptosis pathway.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Furanos/farmacología , Lignanos/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Hep G2 , Humanos , Mitocondrias/metabolismo , Proteómica , Transducción de Señal/efectos de los fármacos
17.
Int J Mol Med ; 37(6): 1465-74, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27082928

RESUMEN

FcγRIIIa (CD16) is a low-affinity Fc receptor of IgG. As the idio-binding receptor of IgG Fc, it plays an important role in the antibody-dependent cellular cytotoxicity of natural killer cells. The aim of the present study was to investigate the distribution of Kupffer cells (KCs) and the expression of their surface receptor FcγRIIIa in hepatocellular carcinoma. Furthermore, we also aimed to observe the functional mechanism of FcγRIIIa. Immunohistochemical analysis was employed to study KCs and FcγRIIIa. In order to explore the role of FcγRIIIa in the growth of cancer cells, KCs and H22 tumor cells were co-cultured in different serum. The mRNA expression levels of tumor necrosis factor (TNF)-α and FcγRIIIa were analyzed by RT-qPCR; the TNF-α and FcγRIIIa protein expression levels were examined by enzyme­linked immunosorbent assay and western blot analysis, respectively. Our results showed that the number of Kuppfer cells in cancerous tissues (21.6±7.8) was lower than those in para-cancerous (68.8±9.1) tissues and adjacent normal hepatic tissues (62.0±1.9) (P<0.01); this decreased with the reduction in the differentiation degree of cancer (P<0.05). FcγRIIIa-positive cells were similar in morphology to KCs, and their distributive tendency was coincident (P<0.05). The increase in CD16a mRNA levels in the group treated with immune serum was 3.9-, 4.9- and 3.9-fold greater than that in the ordinary serum group at different time points, and CD16a protein expression also markedly increased (P<0.05). However, these effects were inhibited by the addition of anti-IgG Fc serum (P<0.05). The results of the present study suggested that FcγRIIIa resided in KCs, and it contributed to the inhibition of the growth of liver tumor cells.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Hepatocitos/inmunología , Macrófagos del Hígado/inmunología , Neoplasias Hepáticas/inmunología , ARN Mensajero/inmunología , Receptores de IgG/inmunología , Animales , Anticuerpos Antiidiotipos/farmacología , Ascitis/genética , Ascitis/inmunología , Ascitis/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Comunicación Celular , Línea Celular Tumoral , Técnicas de Cocultivo , Femenino , Regulación de la Expresión Génica , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Humanos , Sueros Inmunes/farmacología , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones , Cultivo Primario de Células , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/genética , Receptores de IgG/antagonistas & inhibidores , Receptores de IgG/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
18.
Asian Pac J Trop Med ; 9(11): 1078-1083, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27890368

RESUMEN

OBJECTIVE: To discuss the effect of Glycyrrhiza uralensis (G. uralensis) Fisch polysaccharide on growth performance and immunologic function in mice in Ural City, Xinjiang and to provide important data supporting the application of Glycyrrhiza polysaccharide. METHODS: A total of 100 Kunming mice aged 3 weeks old were randomly divided into 5 groups with 20 mice in each group (10 were females and 10 were males). About 0.5 mL normal saline was given to the mice of control group every day and 0.5 mL G. uralensis Fisch polysaccharide was given to the mice of other groups at the concentration of 1, 20, 50 and 100 mg/mL, respectively. The growth performance (average body weight, average daily feed intake and feed efficiency), immune organ indexes (spleen index and thymus index) and immunologic function (serum IL-2, CD4+/CD8+ and the activity of NK cells) of mice in each group were detected continuously. RESULTS: The average body weight, feed efficiency, serum IL-2, CD4+/CD8+ and the activity of NK cells of mice were increased with the increase of administrated time after administrating G. uralensis Fisch polysaccharide and were reached up the largest level on Day 28. At the same time, each index was proportional to the given dose and was significantly higher than those of control group and reached up the largest level at the administrated dose of 100 mg/mL. After administrating G. uralensis Fisch polysaccharide, the spleen index and thymus index of mice were increased with the increase of administrated dose and the spleen index and thymus index of mice administrated with the dose of 100 mg/mL were maximum which was more than 1.51 times and 1.43 times of that in control group, respectively and the comparative differences showed statistical significance (P < 0.05). The average daily feed intake of mice in each group was increased with the passage of time and at the same time, the comparison of average daily feed intake of mice in each group was not significantly different (P > 0.05). CONCLUSIONS: G. uralensis Fisch polysaccharide can significantly improve the growth performance and immunologic function of mice and laid a research basis for the clinical application of G. uralensis Fisch polysaccharide.

19.
Ann Transplant ; 21: 346-9, 2016 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-27251849

RESUMEN

BACKGROUND The aim of this study was to compare the hemodynamic changes in 2 different cannulations in portal system (portal venous catheterization and splenic venous catheterization) during venovenous bypass (VVB) of swine orthotopic liver transplantation (OLT) MATERIAL AND METHODS Thirty pairs (a total of 60) of healthy Duroc pigs were selected for OLT. According to the difference of cannulation in portal venous system during VVB, these pigs were divided into 2 groups: the PVC group (pigs with portal venous catheterization, n=15) and the SVC group (pigs with splenic venous catheterization, n=15). Intraoperative hemodynamic parameters were monitored continuously. RESULTS Two recipients in the PVC group died: 1 died of unsmooth bypass during the operation and 1 died of disseminated intravascular coagulation (DIC). There was only 1 death in the SVC group, due to hemorrhagic shock. The duration of anhepatic phase (AP) in the SVC group was significantly shorter than in the PVC group (P<0.05). Moreover, hemodynamic parameters in phase III (5 min after start of portal vein suturing) and phase IV (5 min after graft reperfusion) were remarkably different between the SVC group and the PVC group (P<0.05). CONCLUSIONS Our results show that VVB via splenic venous catheterization in swine OLT: 1) shortens the AP time; 2) keeps the hemodynamics stable; and 3) reduces the occurrence of postoperative complications. Thus, SVC appears to be superior to PVC.


Asunto(s)
Cateterismo Periférico/métodos , Trasplante de Hígado/métodos , Vena Porta/cirugía , Procedimientos Quirúrgicos Vasculares , Animales , Hemodinámica/fisiología , Porcinos , Vena Cava Inferior/cirugía
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