RESUMO
In oxygenic photosynthetic organisms, light energy is captured by antenna systems and transferred to photosystem II (PSII) and photosystem I (PSI) to drive photosynthesis1,2. The antenna systems of red algae consist of soluble phycobilisomes (PBSs) and transmembrane light-harvesting complexes (LHCs)3. Excitation energy transfer pathways from PBS to photosystems remain unclear owing to the lack of structural information. Here we present in situ structures of PBS-PSII-PSI-LHC megacomplexes from the red alga Porphyridium purpureum at near-atomic resolution using cryogenic electron tomography and in situ single-particle analysis4, providing interaction details between PBS, PSII and PSI. The structures reveal several unidentified and incomplete proteins and their roles in the assembly of the megacomplex, as well as a huge and sophisticated pigment network. This work provides a solid structural basis for unravelling the mechanisms of PBS-PSII-PSI-LHC megacomplex assembly, efficient energy transfer from PBS to the two photosystems, and regulation of energy distribution between PSII and PSI.
Assuntos
Complexos de Proteínas Captadores de Luz , Complexo de Proteína do Fotossistema I , Complexo de Proteína do Fotossistema II , Ficobilissomas , Porphyridium , Transferência de Energia , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/metabolismo , Complexos de Proteínas Captadores de Luz/ultraestrutura , Fotossíntese , Complexo de Proteína do Fotossistema I/química , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema I/ultraestrutura , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/ultraestrutura , Ficobilissomas/química , Ficobilissomas/metabolismo , Ficobilissomas/ultraestrutura , Porphyridium/química , Porphyridium/enzimologia , Porphyridium/metabolismo , Porphyridium/ultraestrutura , Microscopia Crioeletrônica , Imagem Individual de MoléculaRESUMO
Photosynthetic organisms have developed various light-harvesting systems to adapt to their environments1. Phycobilisomes are large light-harvesting protein complexes found in cyanobacteria and red algae2-4, although how the energies of the chromophores within these complexes are modulated by their environment is unclear. Here we report the cryo-electron microscopy structure of a 14.7-megadalton phycobilisome with a hemiellipsoidal shape from the red alga Porphyridium purpureum. Within this complex we determine the structures of 706 protein subunits, including 528 phycoerythrin, 72 phycocyanin, 46 allophycocyanin and 60 linker proteins. In addition, 1,598 chromophores are resolved comprising 1,430 phycoerythrobilin, 48 phycourobilin and 120 phycocyanobilin molecules. The markedly improved resolution of our structure compared with that of the phycobilisome of Griffithsia pacifica5 enabled us to build an accurate atomic model of the P. purpureum phycobilisome system. The model reveals how the linker proteins affect the microenvironment of the chromophores, and suggests that interactions of the aromatic amino acids of the linker proteins with the chromophores may be a key factor in fine-tuning the energy states of the chromophores to ensure the efficient unidirectional transfer of energy.
Assuntos
Microscopia Crioeletrônica , Transferência de Energia , Ficobilissomas/química , Ficobilissomas/ultraestrutura , Porphyridium/química , Porphyridium/ultraestrutura , Proteínas de Algas/química , Proteínas de Algas/metabolismo , Proteínas de Algas/ultraestrutura , Modelos Moleculares , Fotossíntese , Ficobilinas/química , Ficobilinas/metabolismo , Ficobilissomas/metabolismo , Conformação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Rodófitas/química , Rodófitas/ultraestruturaRESUMO
Increasing evidence has demonstrated that lncRNA plays a significant role in the immunity regulation of gastric adenocarcinoma. However, the immune-related lncRNAs and the prognostic value in immunotherapies remain largely unexplored. We collected immune-related lncRNA and the associated pathways of gastric cancer from the ImmLnc database. The cox regression model is used to analyze the prognostic value of these lncRNAs. Gastric cancer is further divided into different subtypes based on these lncRNAs. Tumor microenvironment analysis, functional enrichment analysis, and genomic alteration analysis are performed for different subtypes. Furthermore, chemotherapeutic and immunotherapeutic sensitivity are also analyzed among different subtypes. Nine lncRNAs are identified as significant regulators of the immune pathway of gastric cancer. Gastric cancer can be classified into 5 subtypes based on these lncRNAs. Tumor microenvironment analysis shows that cluster C3 has the highest immune score and C5 has the lowest score. Functional analysis shows that these subtypes are enriched with distinct biological processes. Genomic analysis shows that LAMA2 mutation is a protective factor in C3 but a risk factor in C5. Furthermore, these subtypes are found to respond distinctly to the same chemotherapeutic and immunotherapeutic drugs. In this study, we analyzed the immune-related lncRNA and identified the crucial role in the regulation of immune properties, biological processes, and immunotherapeutic sensitivity. These findings can improve our understanding of the epigenetic immunoregulation of lncRNA and advance the research of immunotherapy.
Assuntos
Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Relevância Clínica , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Adenocarcinoma/genética , Epigenômica , Microambiente Tumoral/genéticaRESUMO
Life on Earth depends on photosynthesis for its conversion of solar energy to chemical energy. Photosynthetic organisms have developed a variety of light-harvesting systems to capture sunlight. The largest light-harvesting complex is the phycobilisome (PBS), the main light-harvesting antenna in cyanobacteria and red algae. It is composed of phycobiliproteins and linker proteins but the assembly mechanisms and energy transfer pathways of the PBS are not well understood. Here we report the structure of a 16.8-megadalton PBS from a red alga at 3.5 Å resolution obtained by single-particle cryo-electron microscopy. We modelled 862 protein subunits, including 4 linkers in the core, 16 rod-core linkers and 52 rod linkers, and located a total of 2,048 chromophores. This structure reveals the mechanisms underlying specific interactions between linkers and phycobiliproteins, and the formation of linker skeletons. These results provide a firm structural basis for our understanding of complex assembly and the mechanisms of energy transfer within the PBS.
Assuntos
Microscopia Crioeletrônica , Ficobilissomas/química , Ficobilissomas/ultraestrutura , Rodófitas/química , Rodófitas/ultraestrutura , Proteínas de Algas/química , Proteínas de Algas/metabolismo , Proteínas de Algas/ultraestrutura , Transferência de Energia , Modelos Moleculares , Ficobilissomas/metabolismo , Subunidades Proteicas/química , Subunidades Proteicas/metabolismoRESUMO
In this study, a one-step method of polyethylenimine (PEI) cross-linking graphene oxide (GO) was used to prepare a 3D pore-structured adsorbent with abundant amine groups for chemisorption of CO2. The cross-linking of PEI with GO sheets and the vacuum freeze-drying step are the keys to the formation of the 3D pore structure. The results of characterization analysis revealed that the as-prepared adsorbent had a 3D porous structure rich in amine groups. Besides, the adsorption/desorption test showed that the prepared adsorbent has excellent and stable adsorption performance, and the maximum CO2 adsorption capacity is 2.18 mmol/g at 343 K and 10 vol % CO2. Moreover, the adsorption kinetics analysis indicated that the adsorption process was dominated by homogeneous adsorption, and the adsorbent had a strong affinity with CO2. Finally, the correlation analysis shows that the kinetic constants obtained by the Avrami model simulation can be effectively used for the actual CO2 adsorption process design.
RESUMO
OBJECTIVE: This study aimed to study the relationship between air pollution and stroke (especially emergency stroke) in different regions and determine which air pollutant is the most significantly associated with stroke. METHODS: The number of patients with emergency stroke, air pollutant data and related meteorological indicators were collected from December 2013 to May 2018 for large comprehensive hospitals in Chongqing. The generalized additive model was used to analyse the relationship between air pollution and emergency stroke. RESULTS: After analysis and adjusting for meteorological indicators and day-of-the-week effects, in the one-pollutant model, every 10 µg/m3 increase in ozone(O3) was associated with a 2.482% (95% CI 1.044%, 3.919%) change in emergency strokes within lag0. For males, every 10 µg/m3 increase of O3 contributed to a 0.77% percent greater change compared with females. For the group younger than 60 years, we observed a 1.14% increase in risk with every 10 µg/m3 increase in O3. The group with pre-existing hypertension had a 0.26% higher risk than the group with no pre-existing hypertension with every 10 µg/m3 increase in O3. In two-pollutant model, when O3 was combined with a 10 µg/m3 increase of NO2, it increased the most significant risk of emergency stroke by 0.22%. CONCLUSION: These findings suggest that short-term exposure to O3 within 0 days is associated with emergency outpatient strokes, and younger people (age < 60 years) males and people with hypertension are more sensitive than older people, females and people without pre-existing hypertension.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Hipertensão/epidemiologia , Ozônio/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China/epidemiologia , Serviço Hospitalar de Emergência , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise , Dióxido de Enxofre/análise , Temperatura , VentoRESUMO
BACKGROUND: Obesity is a metabolic imbalance characterized by excessive deposition of white fat. The browning of white fat can effectively treat obesity and related diseases. Although Dlgap1 (Discs, Large (Drosophila) Homolog-Associated Protein 1) is suspected to have an effect on this process, no empirical evidence is available. METHODS: To understand the role of Dlgap1, we cultured white and brown fat cells, then performed overexpression and knockout experiments. RESULTS: We found that Dlgap1 overexpression in brown adipocytes inhibits brown-fat-related gene expression, promotes white-fat-related genes, while also increasing brown-adipocyte proliferation and apoptosis. However, the gene overexpression has no effect on brown adipocyte maturation. Knocking out Dlgap1 in white fat cells promotes the expression and inhibition of brown-fat-related and white-fat-related genes, respectively. Additionally, the knockout inhibits white fat cell proliferation and apoptosis, while also promoting their maturation. CONCLUSIONS: Dlgap1 negatively regulates the browning of white adipocytes by influencing cell proliferation and apoptosis.
Assuntos
Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Apoptose/fisiologia , Proliferação de Células/fisiologia , Proteínas Associadas SAP90-PSD95/metabolismo , Adipócitos Marrons/citologia , Adipócitos Brancos/citologia , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/metabolismo , Animais , Apoptose/genética , Western Blotting , Proliferação de Células/genética , Camundongos , Proteínas Associadas SAP90-PSD95/genéticaRESUMO
Epithelial-mesenchymal transition(EMT) is the main reason for peritoneal fibrosis and the mechanism underlying peritoneal EMT were extensively studied in recent years. Recent researches showed that miRNAs were so important in the development of organ EMT and fibrosis, the role of microRNAs on peritoneal dialysis have also been studied. In the current study, we investigated microRNA-23(miR-23) expression in high glucose(HG) induced EMT in human mesotheial peritoneal cells(HPMCs). We found that HG promoted EMT, which was characterized by the upregulation of mesenchymal markers α-SMA and FN and downregulation of epithelial marker E-cadherin. The expression miR-23 showed a significant upregulation when treated with HG. Enhanced expression of miR-23 could aggravate HG induced EMT by targeting VDR, inhibition of miR-23 in HPMCs could reverse HG induced EMT by targeting VDR. Furthermore, VDRshRNA exacerbated the EMT process and reversed miR-23 inhibitor-attenuated EMT process in HPMCs. These data manifested that miR-23 played a key role in HG-induced EMT of HPMCs by targeting VDR.
Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Epitélio/efeitos dos fármacos , Glucose/efeitos adversos , MicroRNAs/fisiologia , Peritônio/efeitos dos fármacos , Receptores de Calcitriol/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Epitélio/metabolismo , Epitélio/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/genética , Peritônio/metabolismo , Peritônio/patologiaRESUMO
BACKGROUND/AIMS: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. METHODS: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers. RESULTS: We found that treatment with high Pi levels (1 and 3 mM) activated LC3II expression and promoted autophagic flux in VSMCs. Conversely, treatment with an autophagy inhibitor decreased LC3II expression. Pi stimulation dysregulated the expression of several miRNAs such as miR-18a, miR-21, miR-23a, miR-30b, and miR-31a. However, miR-30b overexpression decreased Pi-induced expression of autophagy-related marker genes such as BECN1, ATG5, and LC3b, whereas miR-30b downregulation increased Pi-induced expression of these genes. In addition, we found that miR-30b directly targeted BECN1. CONCLUSIONS: These data suggest that miR-30b plays an important role in the regulation of high Pi level-induced autophagy in VSMCs by targeting BECN1.
Assuntos
Aorta Torácica/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/biossíntese , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/patologia , Autofagia/genética , Proteína Beclina-1/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/biossíntese , Proteínas Associadas aos Microtúbulos/genética , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fósforo/farmacologia , RatosRESUMO
BACKGROUND: A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus (DM) patients. Nevertheless, the results are inconclusive and inconsistent. METHODS: We screened PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Wanfang databases for those relevant studies updated in May 2016. RESULTS: 7 studies involving 2564 subjects were recruited. We evaluated the genotypic and allelic differences between DN patients and DM controls. Overall analysis showed that no significant association was found among the ApaI, BsmI, FokI,TaqI gene polymorphisms and DN susceptibility in diabetic patients (all P values > 0.05). In the stratified analysis, TT genotype was related to DN susceptibility in Asians (TT vs Tt + tt: OR =2.21, 95% CI: 1.05-4.67, p = 0.04). The sensitivity analysis showed that the results in overall populations, Caucasians and Asians were dependable. CONCLUSIONS: No significant association was found among the ApaI, BsmI, FokI, TaqI polymorphisms and DN risk in overall populations, the TaqI variants might related to DN susceptibility in Asians. Further researches are required to testify our meta-analysis.
Assuntos
Nefropatias Diabéticas/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , HumanosRESUMO
OBJECTIVES: To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine. RESULTS: C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 µg/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4+ T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-γ (458 ± 98 pg/ml), a typical Th1 cytokine. IFN-γ-expressing CD8+ cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization. CONCLUSIONS: A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.
Assuntos
Aciltransferases/imunologia , Adjuvantes Imunológicos , Antígenos de Bactérias/imunologia , Interferon gama/imunologia , Proteínas Recombinantes de Fusão/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinas de DNA/imunologia , Aciltransferases/química , Aciltransferases/genética , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/genética , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/genética , Líquido da Lavagem Broncoalveolar/citologia , Células Cultivadas , Clonagem Molecular , Células HEK293 , Humanos , Interferon gama/química , Interferon gama/genética , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Baço/citologia , Tuberculose , Vacinas contra a Tuberculose/química , Vacinas contra a Tuberculose/genética , Vacinas de DNA/química , Vacinas de DNA/genéticaRESUMO
BACKGROUND/AIMS: Pioglitazone is a type of peroxisome proliferator-activated receptor x03B3; agonist and is capable of alleviating renal ischemia-reperfusion injury. METHODS: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. RESULTS: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. CONCLUSION: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.
Assuntos
Antioxidantes/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , PPAR gama/agonistas , Tiazolidinedionas/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/irrigação sanguínea , Rim/metabolismo , Malondialdeído/análise , Nefrectomia , Óxido Nítrico/análise , PPAR gama/metabolismo , Pioglitazona , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , Superóxido Dismutase/análise , Tiazolidinedionas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-ß/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-ß/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-ß/Smad/EMT signaling activity.
Assuntos
Berberina/uso terapêutico , Rim/efeitos dos fármacos , Animais , Western Blotting , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Rim/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estreptozocina/toxicidade , Fator de Crescimento Transformador beta/metabolismoAssuntos
Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Sarcoidose/diagnóstico por imagem , Sarcoidose/patologia , Diagnóstico por Imagem/métodos , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
AIMS: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. METHODS: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/ß-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of ß-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. RESULTS: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/ß-catenin pathway and ß-catenin activity. ß-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that ß-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that ß-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of ß-catenin in the rat model was investigated, we found that aortic calcification was reduced. CONCLUSION: These results suggest that ß-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.
Assuntos
Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fósforo/farmacologia , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Aorta , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Creatina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Nefrectomia , Osteopontina/genética , Osteopontina/metabolismo , Fósforo na Dieta/metabolismo , Plasmalogênios/sangue , Ratos , Ratos Sprague-Dawley , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismo , Calcificação Vascular/etiologia , beta Catenina/genéticaRESUMO
In order to remediate ammonium contaminated groundwater, an innovative multimedia permeable reactive barrier (M-PRB) was proposed, which consisted of sequential columns combining oxygen releasing compound (ORC), zeolite, spongy iron and pine bark in the laboratory scale. Results showed that both ammonium and nitrate could be reduced to levels below the regulatory discharge limits through ion exchange and microbial degradation (nitrification and denitrification) in different compartments of the M-PRB system. The concentration of dissolved oxygen (DO) increased from 2 to above 20â mg/L after the simulated groundwater flowed through the oxygen releasing column packed with ORC, demonstrating that ORC could supply sufficient oxygen for subsequent microbial nitrification. Ammonium was efficiently removed from about 10 to below 0.5â mgâ N/L in the aerobic reaction column which was filled with biological zeolite. After 54 operating days, more than 70% ammonium could be removed by microbial nitrification in the aerobic reaction column, indicating that the combined use of ion exchange and nitriï¬cation by biological zeolite could ensure high and sustainable ammonium removal efficiency. To avoid the second pollution of nitrate produced by the former nitrification, spongy iron and pine bark were used to remove oxygen and supply organic carbon for heterotrophic denitrification in the oxygen removal column and anaerobic reaction column separately. The concentration of nitrate decreased from 14 to below 5â mgâ N/L through spongy iron-based chemical reduction and microbial denitrification.
Assuntos
Compostos de Amônio/metabolismo , Água Subterrânea , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Adsorção , Compostos de Amônio/química , Biodegradação Ambiental , Desnitrificação , Água Subterrânea/química , Concentração de Íons de Hidrogênio , Troca Iônica , Ferro/química , Nitrificação , Oxigênio/análise , Pinus , Casca de Planta , Poluentes Químicos da Água/química , Zeolitas/químicaRESUMO
OBJECTIVE: This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). METHODS: We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. RESULTS: Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. CONCLUSION: Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients.
Assuntos
Nefropatias Diabéticas/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
This study aimed to investigate the protective effect of metformin on renal injury of C57BL/6J mice treated with a high fat diet. High-fat diet for 12 weeks was used to establish the mice model of metabolism syndrome and the intervention of metformin (75 mg x kg(-1) x d(-1)) for 4 weeks, and plasma biochemical indicator and body weight were used to evaluate the model. Sterol regulatory element-binding protein (SERBP)-1c, TNF-α, NADPH Oxidase (NOX)4 mRNA was determined by real time-PCR. Phospho-AMP-activated protein kinase (P-AMPK)α protein was detected by western blotting. Oil Red O staining, Masson staining and HE staining were for observing renal pathological changes. At the end of 12th week, compared with mice on low fat diet (LFD), body weight (BW), the levels of fasting insulin (FINS), plasma and renal triglyceride (TG) were higher and plasma high density lipoprotein (HDL) and insulin sensitivity index (ISI) were significantly lower, but the levels of fasting blood glycemia (FBG), plasma total cholesterol (TC) and renal TC had no changes; Oil Red O staining revealed renal lipids deposition, Masson staining and HE staining revealed glomerular hypertrophy, matrix increasing, and inflammatory cells infiltration in glomerular; the expression of p-AMPKα protein decreased and the expression of SREBP-1c, TNF-α, NOX4 mRNA increased significantly in mouse treated with high fat diet (HFD). Compared with the HFD group, through metformin interventing, metabolic disorders were significantly improved, renal lipids deposition and other pathological changes were ameliorated, the expression of p-AMPKα protein increased and the expression of SREBP-1c, TNF-α, NOX4 mRNA decreased significantly. Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-α, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Injúria Renal Aguda/patologia , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Rim/metabolismo , Rim/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nefrite/patologia , Nefrite/prevenção & controle , Estresse Oxidativo/efeitos dos fármacosRESUMO
Background: Chondrosarcomas are common primary malignant bone tumors; however, comprehensive bibliometric analysis in this field has not yet been conducted. Therefore, this study aimed to explore the research hotspots and trends in the field of chondrosarcoma through bibliometric analysis to help researchers understand the current status and direction of research in the field. Methods: Articles and reviews related to chondrosarcoma published between 2003 and 2022 were retrieved from the Web of Science. Countries, institutions, authors, journals, references, and keywords in this field were visualized and analyzed using CtieSpace and VOSviewer software. Results: Between 2003 and 2022, 4,149 relevant articles were found. The number of articles published on chondrosarcoma has increased significantly annually, mainly from 569 institutions in China and the United States, and 81 in other countries. In total, 904 authors participated in the publication of studies related to chondrosarcomas. Over the past 20 years, articles on chondrosarcoma have been published in 958 academic journals, with Skeletal Radiology having the highest number of publications. Furthermore, keywords such as "gene expression," "radiotherapy," "experience," and "apoptosis" have been popular in recent years. Conclusion: Over the past 20 years, the global trend in chondrosarcoma research has primarily been clinical research, with basic research as a supplement. In the future, communication and exchange between countries and institutions should be strengthened. Further, the future main research hotspots in the field of chondrosarcoma include mutated genes and signaling pathways, precision surgical treatment, proton therapy, radiation therapy, chemotherapy, immunotherapy, and other aspects.
RESUMO
The mixture of whole-plant soybean and whole-plant corn silage (WPSCS) is nutrient balanced and is also a promising roughage for ruminants. However, few studies have investigated the changes in bacterial community succession in WPSCS inoculated with homofermentative and heterofermentative lactic acid bacteria (LAB) and whether WPSCS inoculated with LAB can improve fermentation quality by reducing nutrient losses. This study investigated the effect of Lactobacillus plantarum (L. plantarum) or Lactobacillus buchneri (L. buchneri) on the fermentation quality, aerobic stability, and bacterial community of WPSCS. A 40:60 ratio of whole-plant soybean corn was inoculated without (CK) or with L. plantarum (LP), L. buchneri (LB), and a mixture of LP and LB (LPB), and fermented for 14, 28, and 56 days, followed by 7 days of aerobic exposure. The 56-day silage results indicated that the dry matter content of the LP and LB groups reached 37.36 and 36.67%, respectively, which was much greater than that of the CK group (36.05%). The pH values of the LP, LB, and LPB groups were significantly lower than those of the CK group (p < 0.05). The ammoniacal nitrogen content of LB was significantly lower than that of the other three groups (p < 0.05), and the ammoniacal nitrogen content of LP and LPB was significantly lower than that of CK (p < 0.05). The acetic acid content and aerobic stability of the LB group were significantly greater than those of the CK, LP, and LPB groups (p < 0.05). High-throughput sequencing revealed a dominant bacteria shift from Proteobacteria in fresh forage to Firmicutes in silage at the phylum level. Lactobacillus remained the dominant genus in all silage. Linear discriminant analysis effect size (LEFSe) analysis identified Lactobacillus as relatively abundant in LP-treated silage and Weissella in LB-treated groups. The results of KEGG pathway analysis of the 16S rRNA gene of the silage microbial flora showed that the abundance of genes related to amino acid metabolism in the LP, LB, and LPB groups was lower than that in the CK group (p < 0.05). In conclusion, LAB application can improve the fermentation quality and nutritional value of WPSCS by regulating the succession of microbial communities and metabolic pathways during ensiling. Concurrently, the LB inoculant showed the potential to improve the aerobic stability of WPSCS.