RESUMO
BACKGROUND: Multiple myeloma (MM) is a malignancy in which plasma cells proliferate abnormally, and it remains incurable. The cells are characterized by high levels of endoplasmic reticulum stress (ERS) and depend on the ERS response for survival. Thus, we aim to find an ERS-related signature of MM and assess its diagnostic value. METHODS: We downloaded three datasets of MM from the Gene Expression Omnibus database. After identifying ERS-related differentially expressed genes (ERDEGs), we analyzed them using Gene Ontology enrichment analysis. A protein-protein interaction network, a transcription factor-mRNA network, a miRNA-mRNA network and a drug-mRNA network were constructed to explore the ERDEGs. The clinical application of these genes was identified by calculating the infiltration of immune cells and using receiver operating characteistic analyses. Finally, qPCR was performed to further confirm the roles of ERDEGs. RESULTS: We obtained nine ERDEGs of MM. Gene Ontology enrichment indicated that the ERDEGs played a role in the endoplasmic reticulum membrane. Additionally, the protein-protein interaction network showed interaction among the ERDEGs, and there were 20 proteins, 107 transcription factors, 42 drugs or molecular compounds and 51 miRNAs which were likely to interact with the nine genes. In addition, immune cell infiltration analyses showed that there was a strong correlation between the nine genes and immune cells, and these potential biomarkers exhibited good diagnostic values. Finally, the expression of ERDEGs in MM cells was different from that in healthy donor samples. CONCLUSION: The nine ERS-related genes, CR2, DHCR7, DNAJC3, KDELR2, LPL, OSBPL3, PINK1, VCAM1 and XBP1 are potential biomarkers of MM, and this supports further clinical development of the diagnosis and treatment of MM.
Assuntos
MicroRNAs , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Estresse do Retículo Endoplasmático/genética , Ontologia Genética , MicroRNAs/genética , Biomarcadores , RNA Mensageiro/genética , Proteínas de Transporte VesicularRESUMO
Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-NX formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N2O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N2O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.
Assuntos
Desnitrificação , Nitritos , Nitritos/metabolismo , Nitritos/farmacologia , Carbono , Anaerobiose , Proteômica , Nitrogênio/metabolismo , Nitrogênio/farmacologiaRESUMO
Shape processing, whether by seeing or touching, is pivotal to object recognition and manipulation. Although the low-level signals are initially processed by different modality-specific neural circuits, multimodal responses to object shapes have been reported along both ventral and dorsal visual pathways. To understand this transitional process, we conducted visual and haptic shape perception fMRI experiments to test basic shape features (i.e. curvature and rectilinear) across the visual pathways. Using a combination of region-of-interest-based support vector machine decoding analysis and voxel selection method, we found that the top visual-discriminative voxels in the left occipital cortex (OC) could also classify haptic shape features, and the top haptic-discriminative voxels in the left posterior parietal cortex (PPC) could also classify visual shape features. Furthermore, these voxels could decode shape features in a cross-modal manner, suggesting shared neural computation across visual and haptic modalities. In the univariate analysis, the top haptic-discriminative voxels in the left PPC showed haptic rectilinear feature preference, whereas the top visual-discriminative voxels in the left OC showed no significant shape feature preference in either of the two modalities. Together, these results suggest that mid-level shape features are represented in a modality-independent manner in both the ventral and dorsal streams.
Assuntos
Reconhecimento Visual de Modelos , Percepção Visual , Reconhecimento Visual de Modelos/fisiologia , Percepção Visual/fisiologia , Lobo Occipital/diagnóstico por imagem , Tato/fisiologia , Lobo Parietal , Imageamento por Ressonância Magnética/métodos , Mapeamento EncefálicoRESUMO
A critical way for humans to acquire information is through language, yet whether and how language experience drives specific neural semantic representations is still poorly understood. We considered statistical properties captured by 3 different computational principles of language (simple co-occurrence, network-(graph)-topological relations, and neural-network-vector-embedding relations) and tested the extent to which they can explain the neural patterns of semantic representations, measured by 2 functional magnetic resonance imaging experiments that shared common semantic processes. Distinct graph-topological word relations, and not simple co-occurrence or neural-network-vector-embedding relations, had unique explanatory power for the neural patterns in the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were relatively specific to language: they were not explained by sensory-motor similarities and the same computational relations of visual objects (based on visual image database) showed effects in the visual cortex in the picture naming experiment. That is, different topological properties within language and the same topological computations (common-neighbors) for language and visual inputs are captured by different brain regions. These findings reveal the specific neural semantic representations along graph-topological properties of language, highlighting the information type-specific and statistical property-specific manner of semantic representations in the human brain.
Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Idioma , Semântica , Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Some nano-biochars (nano-BCs) as electron mediators could enter into cells to directly promote intracellular electron transfer and cell activities. However, little information was available on the effect of nano-BCs on SMX degradation. In this study, nano-BCs were prepared using sludge-derived humic acid (SHA) and their effects on SMX degradation by Shewanella oneidensis MR-1 were investigated. Results showed that nano-BCs (Carbon dots, CDs, <10 nm) synthesized using SHA performed a better accelerating effect than that of the nano-BCs with a larger size (10-100 nm), which could be attributed to the better electron transfer abilities of CDs. The degradation rate of 10 mg/L SMX in the presence of 100 mg/L CDs was significantly increased by 84.6% compared to that without CDs. Further analysis showed that CDs could not only be combined with extracellular Fe(III) to accelerate its reduction, but also participate in the reduction of 4-aminobenzenesulphonic acid as an intermediate metabolite of SMX via coupling with extracellular Fe(III) reduction. Meanwhile, CDs could enter cells to directly participate in intracellular electron transfer, resulting in 32.2% and 25.2% increases of electron transfer system activity and ATP level, respectively. Moreover, the activities of SMX-degrading enzymes located in periplasm and cytoplasm were increased by around 2.2-fold in the presence of CDs. These results provide an insight into the accelerating effect of nano-BCs with the size of <10 nm on SMX degradation and an approach for SHA utilization.
Assuntos
Substâncias Húmicas , Esgotos , Shewanella , Sulfametoxazol , Shewanella/metabolismo , Esgotos/microbiologia , Sulfametoxazol/metabolismo , Anaerobiose , Biodegradação AmbientalRESUMO
BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.
Assuntos
Compostos de Cálcio , Nanofibras , Silicatos , Alicerces Teciduais , Alicerces Teciduais/química , Hidrogéis/farmacologia , Hidrogéis/química , Angiogênese , Regeneração Óssea , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Impressão Tridimensional , Osteogênese , Engenharia TecidualRESUMO
A better understanding of the mechanisms underlying PD-L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD-L1 in forty-five HNSCC archival samples was determined by qRT-PCR. The biological function associated with malignant behaviour was assessed by PD-L1 depletion, miR-382-3p re-expression and regulation of circ_0000052. The interactions of PD-L1-miRNA and miRNA-circRNA were determined by qRT-PCR, Western blot analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. PD-L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD-L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN-γ/JAK2/STAT1 signalling pathway can induce PD-L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD-L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR-382-3p and alleviates its repression of PD-L1. This leads to overexpression of PD-L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR-382-3p/PD-L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti-PD-L1 therapy may improve personalized disease management.
Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias de Cabeça e Pescoço/genética , Evasão da Resposta Imune , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.
Assuntos
Distrofias Musculares , Adulto , Humanos , Hibridização in Situ Fluorescente , Corpos de Inclusão Intranuclear/patologia , Distrofias Musculares/genética , Linhagem , RNA , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
Additional various carbon and free riboflavin could improve anaerobic digestion of waste activated sludge (WAS). However, these substances were not reused. In this study, a reusable riboflavin and carbon black (RCB) co-modified filler was developed and combined with alkaline pretreatment for enhancing the production of volatile fatty acids (VFAs) and methane during anaerobic digestion of WAS. The results showed that RCB-modified fillers exhibited a promoting effect on the reduction of alkali-pretreated WAS. The amounts of the accumulated VFAs mainly containing acetate and the produced methane rose with the increased concentration of immobilized riboflavin (0-0.75 g/L) in the presence of 4 g/L carbon black. When the alkaline pretreatment time of WAS increased from 3 d to 8 d, the amount of methane production increased from 22.8% to 63.9% in the presence of 0.75 g/L riboflavin and 4 g/L carbon black compared with that without RCB-modified fillers. Moreover, 0.75 g/L riboflavin and 4 g/L carbon black had a synergetic effect on promoting methane production via broadening extracellular electron transfer pathways. During this process, microbial dehydrogenase activity, electron transport system activity and coenzyme F420 were enhanced. Microbial community analysis showed that RCB-modified filler addition promoted the enrichment of Syntrophomonas and Pseudomonas involved in direct interspecies electron transfer (DIET). These results indicated that DIET establishment was accelerated. Meanwhile, the populations of acetic acid-producing bacteria including Rikenellaceae_RC9_gut_group and Proteiniphilum, aceticlastic and acid-tolerant methanogenic archaea including Methanosarcina and Methanosaeta, RumEn_M2 were increased. These results indicate that RCB-modified fillers coupled with alkaline pretreatment is an effective method to promote the production of methane during anaerobic digestion of WAS.
Assuntos
Esgotos , Fuligem , Esgotos/microbiologia , Anaerobiose , Reatores Biológicos , Ácidos Graxos Voláteis , Metano , Bacteroidetes , Eliminação de Resíduos Líquidos/métodosRESUMO
Endolymphatic sac tumor (ELST) is a group of low-grade malignant tumors originating from the endolymphatic sac of the inner ear. It is rare in the clinic and has the biological characteristics of slow growth and local aggression. Due to the lack of specificity in the clinical manifestations of patients with ELST, many cases have entered the advanced stage at the time of diagnosis. However, there are still great challenges in the treatment of advanced ELSTs. Here, the authors describe a case of advanced ELST, which relapsed after 2 operations. This time, the authors chose the transotic approach for tumor resection, which achieved the goal of complete resection of the tumor, and the patient recovered smoothly after surgery. There were no surgical complications and no tumor recurrence after the follow-up. Through literature review and our own experience, the authors suggest that complete surgical resection is the first choice for both primary and recurrent advanced ELSTs. The choice of a reasonable surgical approach is the key to ensuring complete resection of the tumor, while preoperative angiography and embolization, fine treatment of important structures during surgery, and postoperative long-term follow-up are equally important for patients with advanced ELST to obtain a good prognosis.
Assuntos
Neoplasias da Orelha , Saco Endolinfático , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Saco Endolinfático/cirurgia , Saco Endolinfático/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/cirurgiaRESUMO
PURPOSE: Cerebellopontine angle meningiomas (CPAMs) are benign tumors that arise from the dura mater of the petrosal surface of the temporal bone, lateral to the trigeminal nerve. This study aimed to describe 1 case of CPAMs violating the mastoid and highlight the unique superiority of the presigmoid transmastoid approach for this type of CPAMs from an otologist's perspective. METHODS: One case of specific CPAMs treated by total resection via presigmoid transmastoid approach in otomicrosurgery was described. RESULTS: A patient was referred for the left intracranial space-occupying lesion found in physical examination. Surgical resection via presigmoid transmastoid approach was performed and there was no sign of recurrence of tumor 2 years after the operation. CONCLUSIONS: Presigmoid transmastoid approach in otomicrosurgery is suitable for CPAMs invading the mastoid. It is suggested that neurosurgeons and ear surgeons should comprehensively analyze the type and extent of the tumor and flexibly adopt surgical methods to ensure it is the best for patients.
Assuntos
Neoplasias Cerebelares , Neoplasias Meníngeas , Meningioma , Neuroma Acústico , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Ângulo Cerebelopontino/diagnóstico por imagem , Ângulo Cerebelopontino/cirurgia , Ângulo Cerebelopontino/patologia , Otorrinolaringologistas , Neoplasias Cerebelares/patologia , Neoplasias Meníngeas/cirurgiaRESUMO
BACKGROUND: This study was to determine the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) and paravertebral block (PVB) as well as the combination of PVB and ESPB (P + E) after video-assisted thoracoscopic surgery (VATS). PATIENTS AND METHODS: Patients were randomly assigned to receive ESPB, PVB or PVB combined with ESPB with 0.5% ropivacaine (20 ml). The primary outcomes were cumulative hydromorphone consumption and Visual Analogue Scale (VAS) scores at rest and while coughing at 0 h, 12 h, 24 h, 48 h and 72 h postoperatively. The secondary outcomes were effective PCA usage count and rescue analgesia requirement at the same time points. RESULTS: The median (interquartile range) hydromorphone consumption, including converted oxycodone, was significantly different at 48 h postoperatively among the three groups (ESPB, 10.24 [9.53-11.71] mg; PVB, 9.94 [9.19-10.75] mg; P + E, 9.44 [8.96-9.97] mg; P = 0.011). Hydromorphone consumption in P + E group was lower compared with that in ESPB group at 12 h, 24 h and 48 h (P < 0.001, P = 0.004 and P = 0.003, respectively). VAS scores at rest were significantly higher for ESPB group compared to P + E group at 0 h postoperatively (P = 0.009). VAS scores while coughing were significantly higher for ESPB group compared to P + E group at 0 h and 12 h postoperatively (P = 0.015 and P < 0.001) and to the PVB group at 12 h postoperatively (P = 0.002). The effective PCA usage count in P + E group was lower than in ESPB group in 0-12 h (P < 0.001). More patients needed rescue analgesia in ESPB group compared to those in P + E group in 0-12 h, 0-24 h and 0-48 h (P = 0.022, 0.035 and 0.035, respectively). CONCLUSIONS: Ultrasound-guided PVB combined with ESPB provided superior analgesia to ESPB for VATS. The combination of PVB and ESPB had a similar analgesic effect compared with PVB alone.
RESUMO
ABSTRACT: Skull base osteomyelitis that is secondary to otitis media is extremely rare in the modern antibiotic era. The authors present an 84-year-old male with atypical skull base osteomyelitis that developed from otitis media during the COVID-19 pandemic due to delayed diagnosis and partial treatment which is blamed for development of skull base osteomyelitis. The atypical presentations of skull base osteomyelitis pose a diagnostic challenge. This case highlights that even otitis media is a potentially fatal infection in older patients with diabetes. Early diagnosis and aggressive management of skull base osteomyelitis are of upmost importance and will ensure a more favorable prognosis.
Assuntos
COVID-19 , Osteomielite , Otite Média , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Tardio , Humanos , Masculino , Osteomielite/diagnóstico , Osteomielite/etiologia , Otite Média/complicações , Otite Média/diagnóstico , Pandemias , SARS-CoV-2 , Base do Crânio/diagnóstico por imagemRESUMO
In the pharmacopoeia, many process parameters for the purification process of Scutellariae Radix are unclear. In this study, deterministic screening design combined with design space method was used to optimize the purification process of Scutellariae Radix extract. Nine method parameters such as mass fraction of solution(X_1), first acid precipitation pH(X_2) and first holding time(X_3) in the purification process were firstly studied by definitive screening design. The yield of baicalin was defined as the evaluation index. A stepwise regression method was used then to build quantitative models between evaluation index and method parameters and the three most critical impact parameters were determined. Probability-based design space was calculated and successfully verified with the experimental error simulation method. Finally, the second standing temperature, the first standing temperature and the pH value of the second acid precipitation were determined as the three most critical method parameters. The recommended operating space was as follows: the second standing temperature 5-7 â, the first standing temperature 13-15 â, and the pH of the second acid precipitation 1.5-1.7. Within this operating space, the baicalin yield in the purification process was over 80%, and the probability of reaching the standard was over 0.96. In this study, we optimized the effect of various parameters for the purification process of the Scutellariae Radix extract in the pharmacopoeia on the yield of baicalin and provided a reference for industrial production of the exact of Scutellariae Radix.
Assuntos
Medicamentos de Ervas Chinesas , Scutellaria baicalensis , Flavonoides , Extratos VegetaisRESUMO
To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.
Assuntos
Doença de Gerstmann-Straussler-Scheinker/genética , Mutação , Proteínas PrPSc/química , Proteínas PrPSc/genética , Doenças Priônicas/genética , Adulto , Alelos , Sequência de Aminoácidos , Animais , Humanos , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Proteínas PrPSc/metabolismo , Domínios Proteicos/genética , Precursores de Proteínas/química , Precursores de Proteínas/genéticaRESUMO
INTRODUCTION: Prion disease is a form of neurodegenerative disease caused by the misfolding and aggregation of cellular prion protein (PrPC). The neurotoxicity of the misfolded form of prion protein, PrPSc still remains understudied. Here we try to investigate this issue using a metabolomics approach. OBJECTIVES: The intention was to identify and quantify the small-in-size and water-soluble metabolites extracted from mice brains infected with the Rocky Mountain Laboratory isolate of mouse-adapted scrapie prions (RML) and track changes in these metabolites during disease evolution. METHODS: A total of 73 mice were inoculated with RML prions or normal brain homogenate control; brains were harvested at 30, 60, 90, 120 and 150 days post-inoculation (dpi). We devised a high-efficiency metabolite extraction method and used nuclear magnetic resonance spectroscopy to identify and quantify 50 metabolites in the brain extracts. Data were analyzed using multivariate approach. RESULTS: Brain metabolome profiles of RML infected animals displayed continuous changes throughout the course of disease. Among the analyzed metabolites, the most noteworthy changes included increases in myo-inositol and glutamine as well as decreases in 4-aminobutyrate, acetate, aspartate and taurine. CONCLUSION: We report a novel metabolite extraction method for lipid-rich tissue. As all the major metabolites are identifiable and quantifiable by magnetic resonance spectroscopy, this study suggests that tracking of neurochemical profiles could be effective in monitoring the progression of neurodegenerative diseases and useful for assessing the efficacy of candidate therapeutics.
Assuntos
Metabolômica/métodos , Príons/metabolismo , Scrapie/metabolismo , Animais , Encéfalo/metabolismo , Progressão da Doença , Feminino , Masculino , Metaboloma/fisiologia , Camundongos , Camundongos Endogâmicos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Príons/química , Scrapie/patologiaRESUMO
Juniperus (Cupressaceae, Pinales) plants are widely distributed in the Qinghai-Tibet Plateau of China. The leaves and twigs of at least 8 Juniperus species (J. pingii, J. pingii var. wilsonii, J. squamata, J. recurva var. coxii, J. saltuaria, J. indica, J. tibetica and J. convallium var. microsperma) have been used as the Tibetan medicine Xuba. At present, it is difficult to distinguish among the original species of Xuba based only on their similar morphological characteristics. However, in our previous studies, 4 Xuba samples from different Juniperus species exhibited significant differences in both anticomplementary activity in vitro and anti-inflammatory effects on acute lung injury in vivo. To identify the effective original species of Xuba reliably, in this study, we developed a sequencing-based DNA molecular technology to distinguish 14 populations of 8 Juniperus species collected from Tibet region, using trnS-G, trnDâ-âT, and petN-psbM genomic regions to build phylogenetic trees. In addition, their anticomplementary activities were evaluated. The results showed that combined sequence of these 3 genomic regions could identify 8 Juniperus species clearly and clustered individuals of one species but from different locations, whichever phylogenetic tree was constructed. Moreover, the anticomplementary activities of the 8 species were clustered into 2 groups. Among them, J. saltuaria and J. recurva var. coxii, which formed an independent branch apart from the other 6 species in phylogenetic trees, were the most potent (CH50: 0.029â-â0.032 mg/mL). Consequently, DNA identification of Juniperus using the combined sequence could provide beneficial guidance for further efficacy evaluation and quality control of Xuba.
Assuntos
Juniperus , China , Cloroplastos , Humanos , Filogenia , TibetRESUMO
Oncocytic Schneiderian papillomas are rare tumours which usually arise in the sinonasal region. This paper presents, to the authors' knowledge, the first reported case of oncocytic Schneiderian papilloma arising primarily from the middle ear and eustachian tube. The resection of the tumor was performed with an endoscopic approach of combined trans oto and nasal. Oncocytic Schneiderian papilloma in the middle ear and eustachian tube is extremely rare as a primary lesion and challenging to manage. Very few documents have provided guide of resection using the endoscopic approach when this tumor extends to involve the eustachian tube. Our study illustrates that the endoscopic approach of combined trans oto and nasal is a good choice for tumor resection of middle ear and eustachian tube.