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1.
Artigo em Inglês | MEDLINE | ID: mdl-39034338

RESUMO

The objective of the study is to investigate the safety, feasibility, and degradation profile of a novel Mg alloy-based bioresorbable coronary scaffold (JFK-PRODUCT BRS) with thin struts (110 µm). Polymer- or Mg alloy-based BRSs have not replaced nondegradable metal stents because of the higher prevalence of scaffold thrombosis and restenosis in clinical practice; these poor clinical outcomes were due to inadequate scaffold designs, including thick struts (more than 150 µm) and their inappropriate degradation processes. Fourteen healthy pigs received 17 JFK-PRODUCT BRSs in the coronary arteries and were sacrificed at 1, 6, 12, 18, and 26 months after implantation. Angiography, optical coherence tomography, microfocus X-ray computed tomography (µCT), scanning electron microscopy with energy-dispersive X-ray spectrometry (SEM-EDX), and histopathological evaluation were performed. The JFK-PRODUCT had a median percent late recoil of 11.28% at 1 month. The µCT observation confirmed that scaffold discontinuity reached 64.8% at 12 months with increased scaffold inner area thereafter, suggesting artery positive remodeling. The inflammation was mild, peaked at 18 months, and decreased thereafter. The SEM-EDX analysis demonstrated gradual degradation of the scaffold with formation of inorganic deposits, presumed to be calcium phosphates. It also revealed the disappearance of calcium phosphates at 26 months, achieving almost complete replacement of the scaffold by biocomponents. The current study demonstrated the safety and feasibility of JFK-PRODUCT with a lower acute recoil rate despite its thin struts. The scaffolds were almost completely disappeared at 26 months after implantation.

2.
Chembiochem ; : e202400352, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073256

RESUMO

Identifying target proteins that interact with bioactive molecules is indispensable for understanding their mechanisms of action. In this study, we developed a uniform ribosome display technology using equal-length DNAs and mRNAs to improve molecular display principle for target identification. The equal-length DNAs were designed to contain various coding sequences for full-length proteins with molecular weights of up to 130 kDa and were used to synthesize equal-length mRNAs, which allowed the formation of full-length protein-ribosome-equal-length mRNA complexes. Uniform ribosome display selections of dihydrofolate reductase and haloalkane dehalogenase mutant were performed against methotrexate and chlorohexane, respectively. Quantitative changes of proteins after each selection indicated that the target protein-displaying ribosomal complexes were specifically selected through non-covalent or covalent interactions with the corresponding bioactive molecules. Furthermore, selection of full-length proteins interacting with methotrexate or anti-DDX46 antibody from protein pools showed that only the target proteins could be precisely identified even though the molar amounts of equal-length mRNAs encoding them were adjusted to 1/20,000 of the total equal-length mRNAs. Thus, the uniform ribosome display technology enabled efficient identification of target proteins that interact with bioactive small and large molecules through simplified operations without deep sequencing.

3.
Genes Cells ; 29(8): 613-634, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38937957

RESUMO

Bacteria use several means to survive under stress conditions such as nutrient depletion. One such response is the formation of hibernating 100S ribosomes, which are translationally inactive 70S dimers. In Gammaproteobacteria (Enterobacterales), 100S ribosome formation requires ribosome modulation factor (RMF) and short hibernation promoting factor (HPF), whereas it is mediated by only long HPF in the majority of bacteria. Here, we investigated the role of HPFs of Comamonas testosteroni, which belongs to the Betaproteobacteria with common ancestor to the Gammaproteobacteria. C. testosteroni has two genes of HPF homologs of differing length (CtHPF-125 and CtHPF-119). CtHPF-125 was induced in the stationary phase, whereas CtHPF-119 conserved in many other Betaproteobacteria was not expressed in the culture conditions used here. Unlike short HPF and RMF, and long HPF, CtHPF-125 could not form 100S ribosome. We first constructed the deletion mutant of Cthpf-125 gene. When the deletion mutant grows in the stationary phase, 70S particles were degraded faster than in the wild strain. CtHPF-125 contributes to stabilizing the 70S ribosome. CtHPF-125 and CtHPF-119 both inhibited protein synthesis by transcription-translation in vitro. Our findings suggest that CtHPF-125 binds to ribosome, and stabilizes 70S ribosomes, inhibits translation without forming 100S ribosomes and supports prolonging life.


Assuntos
Proteínas de Bactérias , Comamonas testosteroni , Proteínas Ribossômicas , Ribossomos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ribossomos/metabolismo , Comamonas testosteroni/metabolismo , Comamonas testosteroni/genética
4.
Nutrients ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674908

RESUMO

Postoperative sarcopenia is associated with poor outcomes in hospitalized patients. However, few studies have focused on short-term postoperative sarcopenia. Furthermore, the influence of nutritional management using amino acids (AAs) comprising a peripheral parenteral nutrition (PPN) solution and its combination with exercise (Exc) is unclear. Hence, we established a postoperative sarcopenic rat model to evaluate the effects of parenteral AA infusion combined with Exc on skeletal muscles and investigate the underlying mechanisms involved in the amelioration of muscle atrophy. Male F344 rats underwent surgery followed by hindlimb suspension (HS) for 5 days. The rats were divided into AA (-), AA (+), AA (-)-Exc, and AA (+)-Exc groups. They were continuously administered a PPN solution with or without AA at 98 kcal/kg/day. The Exc groups were subjected to intermittent loading for 1 h per day. Postoperative sarcopenic rats exhibited decreased muscle strength and mass and an upregulated ubiquitin-proteasome system, autophagy-lysosome system, and fast-twitch fiber-related genes, especially in the AA (-) group. The AA (+)-Exc group exhibited attenuated decreased muscle strength, increased gastrocnemius mass, and a suppressed upregulation of muscle atrophy- and fast-twitch fiber-related genes. Therefore, parenteral AA infusion combined with Exc may be effective in preventing postoperative sarcopenia in hospitalized patients.


Assuntos
Aminoácidos , Modelos Animais de Doenças , Músculo Esquelético , Condicionamento Físico Animal , Ratos Endogâmicos F344 , Sarcopenia , Animais , Sarcopenia/prevenção & controle , Sarcopenia/etiologia , Masculino , Aminoácidos/administração & dosagem , Ratos , Músculo Esquelético/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Atrofia Muscular/prevenção & controle , Atrofia Muscular/etiologia , Força Muscular , Infusões Parenterais , Nutrição Parenteral , Progressão da Doença , Autofagia
5.
JAC Antimicrob Resist ; 6(1): dlad155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38384742

RESUMO

Objectives: In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals. Methods: The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe. Results: A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris. We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo. APC6 disrupted the biofilms formed by Candida species. Conclusions: This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis.

6.
Int J Mol Sci ; 24(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37958644

RESUMO

Cell-free molecular display techniques have been utilized to select various affinity peptides from peptide libraries. However, conventional techniques have difficulties associated with the translational termination through in-frame UAG stop codons and the amplification of non-specific peptides, which hinders the desirable selection of low-affinity peptides. To overcome these problems, we established a scheme for ribosome display selection of peptide epitopes bound to monoclonal antibodies and then applied genetic code expansion with synthetic X-tRNAUAG reprogramming of the UAG codons (X = Tyr, Trp, or p-benzoyl-l-phenylalanine (pBzo-Phe)) to the scheme. Based on the assessment of the efficiency of in vitro translation with X-tRNAUAG, we carried out ribosome display selection with genetic code expansion using Trp-tRNAUAG, and we verified that affinity peptides could be identified efficiently regardless of the presence of UAG codons in the peptide coding sequences. Additionally, after evaluating the photo-cross-linking reactions of pBzo-Phe-incorporated peptides, we performed ribosome display selection of low-affinity peptides in combination with genetic code expansion using pBzo-Phe-tRNAUAG and photo-irradiation. The results demonstrated that sub-micromolar low-affinity peptide epitopes could be identified through the formation of photo-induced covalent bonds with monoclonal antibodies. Thus, the developed ribosome display techniques could contribute to the promotion of diverse peptide-based research.


Assuntos
Código Genético , Ribossomos , Códon de Terminação/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Epitopos/metabolismo
7.
ACS Infect Dis ; 9(7): 1303-1309, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37321567

RESUMO

Artemisinins have been used as first-line drugs worldwide to treat malaria caused by Plasmodium falciparum; however, its underlying mechanism is still unclear. This study aimed to identify the factors inducing growth inhibition via pyknosis, a state of intraerythrocytic developmental arrest, when exposing the parasite to dihydroartemisinin (DHA). Changes in the expression of genome-wide transcripts were assessed in the parasites treated with antimalarials, revealing the specific downregulation of zinc-associated proteins by DHA. The quantification of zinc levels in DHA-treated parasite indicated abnormal zinc depletion. Notably, the zinc-depleted condition in the parasite produced by a zinc chelator induced the generation of a pyknotic form and the suppression of its proliferation. The evaluation of the antimalarial activity of DHA or a glutathione-synthesis inhibitor in the zinc-depleted state showed that the disruption of zinc and glutathione homeostasis synergistically potentiated the growth inhibition of P. falciparum through pyknosis. These findings could help further understand the antimalarial actions of artemisinins for advancing malaria therapy.


Assuntos
Antimaláricos , Artemisininas , Antagonistas do Ácido Fólico , Malária Falciparum , Malária , Parasitos , Animais , Humanos , Antimaláricos/farmacologia , Plasmodium falciparum , Artemisininas/farmacologia , Malária Falciparum/tratamento farmacológico , Malária/tratamento farmacológico , Homeostase , Glutationa
8.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36834855

RESUMO

Ribosomal protein bL31 in Escherichia coli was initially detected as a short form (62 amino acids) using Kaltschmidt and Wittmann's two-dimensional polyacrylamide gel electrophoresis (2D PAGE), but the intact form (70 amino acids) was subsequently identified by means of Wada's improved radical-free and highly reducing (RFHR) 2D PAGE, which was consistent with the analysis of its encoding gene rpmE. Ribosomes routinely prepared from the K12 wild-type strain contained both forms of bL31. ΔompT cells, which lack protease 7, only contained intact bL31, suggesting that protease 7 cleaves intact bL31 and generates short bL31 during ribosome preparation from wild-type cells. Intact bL31 was required for subunit association, and its eight cleaved C-terminal amino acids contributed to this function. 70S ribosomes protected bL31 from cleavage by protease 7, but free 50S did not. In vitro translation was assayed using three systems. The translational activities of wild-type and ΔrpmE ribosomes were 20% and 40% lower than those of ΔompT ribosomes, which contained one copy of intact bL31. The deletion of bL31 reduces cell growth. A structural analysis predicted that bL31 spans the 30S and 50S subunits, consistent with its functions in 70S association and translation. It is important to re-analyze in vitro translation with ribosomes containing only intact bL31.


Assuntos
Escherichia coli , Proteínas Ribossômicas , Proteínas Ribossômicas/metabolismo , Escherichia coli/metabolismo , Ribossomos/metabolismo , Peptídeo Hidrolases/metabolismo , Aminoácidos/metabolismo
9.
JPEN J Parenter Enteral Nutr ; 47(3): 399-407, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597725

RESUMO

BACKGROUND: Nutrition therapy and administration of albumin preparations are common in postsurgical patients. However, the effects of these interventions on albumin metabolism are unclear. We elucidated the effect of postoperative albumin and/or parenteral nutrition administration on it. METHODS: Sprague-Dawley rats underwent surgery involving intestinal rubbing followed by intestinal exposure. Subsequently, they were administered experimental solutions for 48 h, their blood samples were collected at 24 and 48 h, and livers were excised at 48 h. Based on experimental solutions, rats were divided into five groups: non-surgical (Non-surg); glucose and electrolyte solution (GE); amino acid, glucose, and electrolyte solution (AGE); GE + rat serum albumin (Alb) (GE + Alb); and AGE + Alb. Their plasma albumin concentrations; albumin fractional synthesis rate (ALB FSR); mercaptoalbumin/total albumin ratio (MA ratio); and messenger RNA (mRNA) expressions of albumin and hepatocyte nuclear factor-1 (HNF-1) in the liver were measured. RESULTS: The GE and AGE groups showed significant decline in albumin concentrations. ALB FSR was significantly enhanced in the AGE group compared with the GE group. The mRNA expression of albumin was similar to ALB FSR in all groups and that of HNF-1 was significantly decreased in the GE + Alb and AGE + Alb groups compared with the Non-surg group. The MA ratio in the AGE group was similar to the Non-surg group. CONCLUSION: The administration of amino acids comprising parenteral nutrition after surgery augmented ALB FSR and maintained the MA ratio only without simultaneous albumin administration.


Assuntos
Albuminas , Aminoácidos , Eletrólitos , Estresse Fisiológico , Animais , Ratos , Aminoácidos/metabolismo , Aminoácidos/uso terapêutico , Glucose , Ratos Sprague-Dawley , RNA Mensageiro , Albuminas/metabolismo , Albuminas/uso terapêutico
10.
Radiat Prot Dosimetry ; 198(13-15): 964-970, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083754

RESUMO

A tractor-based robot with the capability of real-time assessing and visualizing the radioactive material density and fertility distribution of farmlands has been developed to accelerate the recovery process of the farmlands suffered by the accident of the Fukushima Daiichi Nuclear Power Plant (FDNPP). In a field test at a decontaminated farmland near FDNPP, within-field heterogeneities of soil contamination and fertility are clarified almost in real-time. Results obtained by this robot are consistent with the map by the conventional soil sampling or the history of decontamination activities.


Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação , Robótica , Poluentes Radioativos do Solo , Radioisótopos de Césio/análise , Fazendas , Fertilidade , Japão , Centrais Nucleares , Monitoramento de Radiação/métodos , Solo , Poluentes Radioativos do Solo/análise
11.
J Nutr Sci Vitaminol (Tokyo) ; 68(4): 276-283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047099

RESUMO

ß-Hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, is known to increase muscle mass and strength. However, the effect of perioperative HMB supplementation in liver surgery is unclear. Moreover, the impact of HMB on the skeletal muscle fiber type also remains unclear. We investigated the impact of HMB on the body composition and skeletal muscle fiber type in sarcopenic rats undergoing major hepatectomy. Nine-week-old male F344/NSlc rats were maintained in hindlimb suspension (HLS) and were forcedly supplemented with HMB calcium salt (HMB-Ca, 0.58 g/kg×2 times) or distilled water in addition to free feeding. After 2 wk of HLS, the rats underwent 70% hepatectomy and were sacrificed 3 d after surgery. Body composition factors and the proportion of slow-twitch fibers in hindlimb muscles were evaluated. HMB maintained the body composition and hindlimb force and acted against their deterioration in sarcopenic rats, exerting a particular effect on lean mass weight, which was significant. In the histological study, HMB significantly increased the proportion of slow-twitch fibers in the soleus (p=0.044) and plantaris (p=0.001) of sarcopenic rats. HMB ameliorated deterioration of the body composition and increased the proportion of slow-twitch fibers in sarcopenic rats undergoing major hepatectomy.


Assuntos
Sarcopenia , Animais , Suplementos Nutricionais , Hepatectomia , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Endogâmicos F344 , Sarcopenia/prevenção & controle , Valeratos
12.
Materials (Basel) ; 15(9)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35591466

RESUMO

Magnesium (Mg) alloy has attracted significant attention as a bioresorbable scaffold for use as a next-generation stent because of its mechanical properties and biocompatibility. However, Mg alloy quickly degrades in the physiological environment. In this study, we investigated whether applying a parylene C coating can improve the corrosion resistance of a Mg alloy stent, which is made of 'Original ZM10', free of aluminum and rare earth elements. The coating exhibited a smooth surface with no large cracks, even after balloon expansion of the stent, and improved the corrosion resistance of the stent in cell culture medium. In particular, the parylene C coating of a hydrofluoric acid-treated Mg alloy stent led to excellent corrosion resistance. In addition, the parylene C coating did not affect a polymer layer consisting of poly(ε-caprolactone) and poly(D,L-lactic acid) applied as an additional coating for the drug release to suppress restenosis. Parylene C is a promising surface coating for bioresorbable Mg alloy stents for clinical applications.

13.
ACS Infect Dis ; 8(3): 457-462, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35090116

RESUMO

The infectious protozoan parasite Entamoeba histolytica is responsible for amebiasis causing colitis and liver abscesses, which is an epidemic in developing countries. To develop a drug discovery strategy targeting the iron source required for the proliferation of E. histolytica, an untapped chemical group consisting of low-molecular-weight compounds with metal-binding affinity was investigated. Electrochemically neutral polypyridine compounds, PHN-R2, that showed specific Fe(II)-binding affinity and growth inhibitory ability against E. histolytica were identified. Furthermore, the iron-dependent IC50 values of PHN-R2 and the spectrometric analytical data of their iron complexes clarified the relationship between the antiamebic activity and the iron-targeting specificity. Notably, when PHN-H2 was administrated to E. histolytica-infected hamsters as an animal model of amebiasis, it exhibited a prominent therapeutic efficacy to completely cure liver abscesses without serious side effects. Deciphering the antiamebic activity of iron-targeting compounds in vitro and in vivo provides valuable insights into the development of a next-generation drug against amebiasis.


Assuntos
Amebíase , Entamoeba histolytica , Parasitos , Amebíase/tratamento farmacológico , Animais , Cricetinae , Descoberta de Drogas , Ferro
14.
J Neuroendovasc Ther ; 16(7): 361-365, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37502346

RESUMO

Objective: We report a rare case of pterygopalatine fossa arterial venous shunt disease with venous congestion of the superior ophthalmic vein (SOV) that was treated by transarterial balloon-assisted embolization. Case Presentation: A 57-year-old man presented with congestion of the right bulbar conjunctiva, protrusion, and swelling of the right eyelid was admitted to our hospital. Angiography demonstrated an arteriovenous fistula (AVF) forming small congregated vessels in the pterygopalatine fossa fed by the branch of the ophthalmic artery (OA) and artery of the superior orbital fissure, draining into the SOV via the inferior ophthalmic vein (IOV). From the artery of the superior orbital fissure, transarterial embolization (TAE) with ONYX using a dual-lumen balloon catheter was performed. The patient was treated without complications. Conclusion: TAE using transarterial balloon-assisted embolization with ONYX is effective for periorbital arteriovenous shunts, although special care is necessary to prevent the migration of ONYX into the OA.

15.
Neuropsychopharmacol Rep ; 42(1): 32-41, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964309

RESUMO

AIM: Clozapine is currently the only effective drug for treatment-resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine. METHODS: First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine-binding proteins in extracts from the cerebra of 7-week-old ICR mice were isolated and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy. RESULTS: Alpha and ß tubulins were the most abundant clozapine-binding proteins. We also found that clozapine directly binds with α and ß tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells. CONCLUSION: These results suggest that α and ß tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.


Assuntos
Clozapina , Tubulina (Proteína) , Animais , Cromatografia Líquida , Clozapina/farmacologia , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos ICR , Microtúbulos/metabolismo , Espectrometria de Massas em Tandem , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia
16.
Front Mol Biosci ; 8: 661691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012979

RESUMO

One of the important cellular events in all organisms is protein synthesis, which is catalyzed by ribosomes. The ribosomal activity is dependent on the environmental situation of the cell. Bacteria form 100S ribosomes, lacking translational activity, to survive under stress conditions such as nutrient starvation. The 100S ribosome is a dimer of two 70S ribosomes bridged through the 30S subunits. In some pathogens of gammaproteobacteria, such as Escherichia coli, Yersinia pestis, and Vibrio cholerae, the key factor for ribosomal dimerization is the small protein, ribosome modulation factor (RMF). When ribosomal dimerization by RMF is impaired, long-term bacterial survival is abolished. This shows that the interconversion system between active 70S ribosomes and inactive 100S ribosomes is an important survival strategy for bacteria. According to the results of several structural analyses, RMF does not directly connect two ribosomes, but binds to them and changes the conformation of their 30S subunits, thus promoting ribosomal dimerization. In this study, conserved RMF amino acids among 50 bacteria were selectively altered by mutagenesis to identify the residues involved in ribosome binding and dimerization. The activities of mutant RMF for ribosome binding and ribosome dimerization were measured using the sucrose density gradient centrifugation (SDGC) and western blotting methods. As a result, some essential amino acids of RMF for the ribosomal binding and dimerization were elucidated. Since the induction of RMF expression inhibits bacterial growth, the data on this protein could serve as information for the development of antibiotic or bacteriostatic agents.

17.
Front Psychiatry ; 12: 653821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815179

RESUMO

Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37-0.70) vs. 0.87 (0.47-1.23), p = 0.01; IP-10, 13.99 (8.00-36.64) vs. 30.29 (10.23-134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84-4.48) vs. 1.94 (1.39-2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia.

18.
World Neurosurg ; 144: 112-114, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32889179

RESUMO

BACKGROUND: Although traumatic dural arteriovenous fistula (AVF) is a rare condition, dural injury associated with skull fracture is one of the major factors for the formation of dural AVF at the skull fracture area. We report a case of de novo intraosseous AVF around the anterior condylar confluence after head injury associated with skull base fracture. CASE DESCRIPTION: A woman in her 70s presented with pulsatile tinnitus 3 months after cerebellar infarction and occipital bone fracture. The appearance of de novo intraosseous AVF was confirmed by magnetic resonance imaging and magnetic resonance angiography and treated with coil embolization, which led to symptomatic relief without recurrence on follow-up. CONCLUSIONS: There is no previous report to our knowledge of intraosseous AVF around the anterior condylar confluence proven to appear after skull fracture. This case demonstrates that head injury associated with skull base fracture could be one etiology of dural AVF around the anterior condylar confluence.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/etiologia , Osso Occipital/lesões , Fraturas Cranianas/complicações , Idoso , Tratamento Conservador , Embolização Terapêutica , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Base do Crânio/lesões , Zumbido/terapia
19.
Genes Cells ; 25(8): 562-581, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32559334

RESUMO

When a cell is zinc-deficient, ykgM and ykgO, which encode paralogs of the zinc-binding ribosomal proteins L31 and L36, are expressed from the ykgM operon, which is ordinarily held inactive by the Zur repressor. In ribosomes lacking L31, ribosomal subunit association is weakened, resulting in reduced in vitro translation and the deletion mutants of rpmE, the gene encoding L31, forming small colonies. We isolated four suppressor mutants of ∆rpmE that formed normal colonies. All four mutation sites were located in zur, and ribosomes of zur mutant cells contained one copy of YkgM and had translational activities equivalent to those of ribosomes containing L31. L36 is highly conserved among bacteria, chloroplast and mitochondria. Analysis of a deletion mutant of rpmJ, which encodes L36, suggested that L36 is involved in late assembly of the 50S particle, in vitro translation and cell growth. In zur mutant cells lacking rpmJ, the paralog YkgO was expressed and took over the functions of L36. zur mutant cells contained four types of ribosomes containing combinations of L31 or YkgM, and L36 or YkgO. Copy numbers of L31 and YkgM, and L36 and YkgO, summed to 1, indicating that each paralog pair shares a binding site.


Assuntos
Proteínas de Escherichia coli/metabolismo , Proteínas Ribossômicas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Proteômica/métodos , Proteínas Ribossômicas/genética , Subunidades Ribossômicas/genética , Subunidades Ribossômicas/metabolismo , Ribossomos/metabolismo , Zinco/análise
20.
Front Genet ; 10: 1153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31867037

RESUMO

Transcription and translation in growing phase of Escherichia coli, the best-studied model prokaryote, are coupled and regulated in coordinate fashion. Accordingly, the growth rate-dependent control of the synthesis of RNA polymerase (RNAP) core enzyme (the core component of transcription apparatus) and ribosomes (the core component of translation machinery) is tightly coordinated to keep the relative level of transcription apparatus and translation machinery constant for effective and efficient utilization of resources and energy. Upon entry into the stationary phase, transcription apparatus is modulated by replacing RNAP core-associated sigma (promoter recognition subunit) from growth-related RpoD to stationary-phase-specific RpoS. The anti-sigma factor Rsd participates for the efficient replacement of sigma, and the unused RpoD is stored silent as Rsd-RpoD complex. On the other hand, functional 70S ribosome is transformed into inactive 100S dimer by two regulators, ribosome modulation factor (RMF) and hibernation promoting factor (HPF). In this review article, we overview how we found these factors and what we know about the molecular mechanisms for silencing transcription apparatus and translation machinery by these factors. In addition, we provide our recent findings of promoter-specific transcription factor (PS-TF) screening of the transcription factors involved in regulation of the rsd and rmf genes. Results altogether indicate the coordinated regulation of Rsd and RMF for simultaneous hibernation of transcription apparatus and translation machinery.

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