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1.
mSphere ; : e0025924, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860762

RESUMO

Climate change is rapidly transforming Arctic landscapes where increasing soil temperatures speed up permafrost thaw. This exposes large carbon stocks to microbial decomposition, possibly worsening climate change by releasing more greenhouse gases. Understanding how microbes break down soil carbon, especially under the anaerobic conditions of thawing permafrost, is important to determine future changes. Here, we studied the microbial community dynamics and soil carbon decomposition potential in permafrost and active layer soils under anaerobic laboratory conditions that simulated an Arctic summer thaw. The microbial and viral compositions in the samples were analyzed based on metagenomes, metagenome-assembled genomes, and metagenomic viral contigs (mVCs). Following the thawing of permafrost, there was a notable shift in microbial community structure, with fermentative Firmicutes and Bacteroidota taking over from Actinobacteria and Proteobacteria over the 60-day incubation period. The increase in iron and sulfate-reducing microbes had a significant role in limiting methane production from thawed permafrost, underscoring the competition within microbial communities. We explored the growth strategies of microbial communities and found that slow growth was the major strategy in both the active layer and permafrost. Our findings challenge the assumption that fast-growing microbes mainly respond to environmental changes like permafrost thaw. Instead, they indicate a common strategy of slow growth among microbial communities, likely due to the thermodynamic constraints of soil substrates and electron acceptors, and the need for microbes to adjust to post-thaw conditions. The mVCs harbored a wide range of auxiliary metabolic genes that may support cell protection from ice formation in virus-infected cells. IMPORTANCE: As the Arctic warms, thawing permafrost unlocks carbon, potentially accelerating climate change by releasing greenhouse gases. Our research delves into the underlying biogeochemical processes likely mediated by the soil microbial community in response to the wet and anaerobic conditions, akin to an Arctic summer thaw. We observed a significant shift in the microbial community post-thaw, with fermentative bacteria like Firmicutes and Bacteroidota taking over and switching to different fermentation pathways. The dominance of iron and sulfate-reducing bacteria likely constrained methane production in the thawing permafrost. Slow-growing microbes outweighed fast-growing ones, even after thaw, upending the expectation that rapid microbial responses to dominate after permafrost thaws. This research highlights the nuanced and complex interactions within Arctic soil microbial communities and underscores the challenges in predicting microbial response to environmental change.

2.
Biol Direct ; 19(1): 30, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654256

RESUMO

BACKGROUND: Large bone defects pose a clinical treatment challenge; inhibiting transferrin receptor 2 (TfR2), which is involved in iron metabolism, can promote osteogenesis. Iron-based metal-organic frameworks (MOF-Fe) particles not only inhibit TfR2 but also serve as biomimetic catalysts to remove hydrogen peroxide in reactive oxygen species (ROS); excess ROS can disrupt the normal functions of osteoblasts, thereby hindering bone regeneration. This study explored the potential effects of MOF-Fe in increasing osteogenic activity and clearing ROS. METHODS: In vitro experiments were performed to investigate the osteogenic effects of MOF-Fe particles and assess their impact on cellular ROS levels. To further validate the role of MOF-Fe in promoting bone defect repair, we injected MOF-Fe suspensions into the femoral defects of SD rats and implanted MOF-Fe-containing hydrogel scaffolds in rabbit cranial defect models and observed their effects on bone healing. RESULTS: In vitro, the presence of MOF-Fe significantly increased the expression levels of osteogenesis-related genes and proteins compared to those in the control group. Additionally, compared to those in the untreated control group, the cells treated with MOF-Fe exhibited a significantly increased ability to remove hydrogen peroxide from ROS and generate oxygen and water within the physiological pH range. In vivo experiments further confirmed the positive effect of MOF-Fe in promoting bone defect repair. CONCLUSION: This study supports the application of MOF-Fe as an agent for bone regeneration, particularly for mitigating ROS and activating the bone morphogenetic protein (BMP) pathway, demonstrating its potential value.


Assuntos
Proteína Morfogenética Óssea 2 , Regeneração Óssea , Osteogênese , Ratos Sprague-Dawley , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Ratos , Regeneração Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Estruturas Metalorgânicas/química , Receptores da Transferrina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peroxidase/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Peróxido de Hidrogênio , Masculino
3.
Int J Biol Macromol ; 257(Pt 2): 128808, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101666

RESUMO

Mangrove-derived fungi have been demonstrated to be promising source of structurally diverse and widely active secondary metabolites. During our search for new bioactive compounds, eight new indole-benzodiazepine-2,5-dione derivatives asperdinones A-H (1-8) and two known congeners (9 and 10) were isolated from the culture extracts of the mangrove-derived fungus Aspergillus spinosus WHUF0344 guided by one strain many compounds (OSMAC) and the heteronuclear 1H, 13C single-quantum coherence (HSQC) based small molecule accurate recognition technology (SMART) strategies. The structures and absolute configurations of the new compounds were elucidated by detailed spectroscopic analyze and electronic circular dichroism (ECD) calculations. The putative biosynthetic pathway of these compounds was proposed. Compounds 1-10 were evaluated for their antibacterial and α-glucosidase inhibitory activities. None of compounds showed antibacterial activity. Compounds 2-6 and 8 exhibited moderate inhibitory effects against α-glucosidase with IC50 values in the range of 24.65-312.25 µM. Besides, both 3 and 4 inhibited α-glucosidase variedly. Furthermore, the molecular docking study showed that compounds 2-4 were perfectly docking into the active sites of α-glucosidase. This study not only enriched the chemical diversity of secondary metabolites from the mangrove-derived fungi, but also provided potential hit compounds for further development of α-glucosidase inhibitors.


Assuntos
Aspergillus , Benzodiazepinas , alfa-Glucosidases , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Fungos/metabolismo , Dicroísmo Circular , Indóis , Inibidores de Glicosídeo Hidrolases/química , Antibacterianos/farmacologia , Antibacterianos/química , Estrutura Molecular
4.
J Dermatolog Treat ; 34(1): 2241940, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37551680

RESUMO

PURPOSE: Nail bed atrophy, a common condition for which conservative treatments have limited efficacy, continues to present challenges in determining the optimal surgical intervention. This study introduces a novel technique for nail bed expansion. MATERIALS AND METHODS: A total of 34 patients with nail bed atrophy, selected between 2015 and 2020 (ChiCTR2000036232), were randomized into a control group (n = 17) and a surgical group (n = 17). While no specialized treatment was administered to the control group, the surgical group underwent continuous W-shaped incisions on the ventral side of the digits. RESULTS: Following a 12-month follow-up period, changes in nail bed height, width, area, esthetic satisfaction, pain levels, and tactile sensation were assessed in both groups. In the surgical group, the height, width, and area of the nail bed increased significantly by 1.50 ± 0.49 times, 1.16 ± 0.23 times, and 1.69 ± 0.60 times, respectively, compared to the preoperative measurements. The newly-formed nail plate exhibited improved esthetics, characterized by its smoothness and transparency, a marked improvement over the control group (p < 0.05). Furthermore, this surgical approach showed significant effects, regardless of whether it was applied to fingers or toes. CONCLUSION: The continuous W-shaped incision technique demonstrated substantial benefits and could be a practical therapeutic approach for nail bed enlargement.


Assuntos
Doenças da Unha , Unhas , Humanos , Unhas/cirurgia , Doenças da Unha/cirurgia , Dedos , Estética
5.
Mar Life Sci Technol ; 5(2): 232-241, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37275544

RESUMO

Metabolites of microorganisms have long been considered as potential sources for drug discovery. In this study, five new depsidone derivatives, talaronins A-E (1-5) and three new xanthone derivatives, talaronins F-H (6-8), together with 16 known compounds (9-24), were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362. The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher's method. Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring. A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin. The antimicrobial activity assay indicated that compounds 5, 9, 10, and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration (MIC) values in the range of 2.42-36.04 µmol/L. While secalonic acid D (19) demonstrated significant antimicrobial activity against four strains of H. pylori with MIC values in the range of 0.20 to 1.57 µmol/L. Furthermore, secalonic acid D (19) exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC50 values of 0.15 and 0.19 µmol/L, respectively. The structure-activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H. pylori. The depsidone derivatives are promising leads to inhibit H. pylori and provide an avenue for further development of novel antibiotics. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00170-5.

6.
ACS Biomater Sci Eng ; 9(5): 2596-2607, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36947498

RESUMO

Bone morphogenetic protein (BMP) is a growth factor that effectively promotes osteogenesis. Microsphere-based drug-delivery systems can facilitate an increase in the local concentration of BMP, thus promoting bone formation. In this study, calcium phosphate silicate (CPS) microspheres were used as drug-loading systems for BMP. Three groups─CPS, CPS + BMP, and CPS + BMP + soy lecithin (SL)─were set up, where SL was used to prolong the osteogenic effect of the microsphere system. Bone marrow mesenchymal stem cells and femoral defects in rats were used to compare the osteogenic ability of the three groups. The results indicated that CPS microspheres were good carriers of BMP, facilitating a smoother release into the cells and tissues. SL loading improved the loading rate of BMP, which promoted the osteogenic effect of the microspheres with BMP. We propose CPS microspheres as potential drug-delivery systems that can be effectively used in the treatment of bone defects.


Assuntos
Glycine max , Lecitinas , Ratos , Animais , Microesferas , Glycine max/metabolismo , Preparações de Ação Retardada/farmacologia , Fosfatos , Proteína Morfogenética Óssea 2/metabolismo , Proteínas Morfogenéticas Ósseas , Regeneração Óssea , Fosfatos de Cálcio , Silicatos/farmacologia
7.
Disabil Rehabil ; 45(24): 4148-4155, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36373170

RESUMO

PURPOSE: Patients with scar contracture deformities caused by hand burns were treated with an exoskeleton manipulator system, which was equipped with games to explore its clinical application value. METHODS: Twenty patients who were treated for post-burn scars of bilateral hands between October 2020 and June 2021 were selected (ChiCTR2000036232). The patients were divided into two groups: control, 10 patients (traditional outpatient treatment); and experimental, 10 patients (exoskeleton manipulator system treatment). We compared the change in the total active motion (TAM) value, grip strength, scar improvement, and postoperative pain improvement. RESULTS: After 3 months of rehabilitation training, the improvement of thumb TAM was 33.80 ± 11.38 ° in the experimental group and 23.2 ± 6.13 ° in the control group. With respect to the index finger TAM, the improvement in the experimental and control groups was 84.50 ± 30.96 ° and 54.80 ± 15.89 °, respectively. The middle finger TAM of the experimental and control groups improved by 86.75 ± 32.85 ° and 60.25 ± 17.97 °, respectively. However, improvement of grip strength, scar score, and pain score were similar between the two groups. CONCLUSIONS: The exoskeleton manipulator system has excellent effects in improving burned hand joint movement, which is suitable for hand burn patients and has beneficial clinical effects.Implications for rehabilitationExercise is an effective means to improve the hand function of burn patients.The application of mechanical devices in the rehabilitation of burned hands can effectively help patients exercise.The A5 Hand Function Training System is an exoskeleton mechanical device that can exercise the small joints of the hand. It assists patients in using different computer games during treatment.


Assuntos
Exoesqueleto Energizado , Traumatismos da Mão , Traumatismos do Punho , Humanos , Cicatriz , Traumatismos da Mão/reabilitação , Mãos , Força da Mão
8.
Arch Dermatol Res ; 315(5): 1257-1267, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36526799

RESUMO

Abnormal fibroblast proliferation and excessive extracellular matrix (ECM) deposition lead to the formation of hypertrophic scars (HSs). However, there is no satisfactory method to inhibit the occurrence and development of HSs. In our study, platycodin D (PD), a natural compound extracted from Platycodon grandiflorus, inhibited HSs formation both in vitro and in vivo. First, qRT-PCR and Western blot were used to confirm PD dose-dependently downregulated the expression of Col I, Col III and α-SMA in human hypertrophic scar-derived fibroblasts (HSFs) (p < 0.05). Second, cck-8, transwell and wound healing assays verified PD suppressed the proliferation (p < 0.05) and migration of HSFs (p < 0.05), and inhibited the differentiation of HSFs into myofibroblasts. Moreover, PD-induced HSFs apoptosis were analyzed by flow cytometry and the apoptosis was activated through a caspase-dependent pathway. The rabbit ear scar model was used to further confirm the inhibitory effect of PD on collagen and α-SMA deposition. Finally, Western blot analysis showed that PD reduced TGF-ß RI expression (p < 0.05) and affected matrix metalloproteinase 2 (MMP2) protein levels (p < 0.05). In conclusion, our study showed that PD inhibited the proliferation and migration of HSFs by inhibiting fibrosis-related molecules and promoting apoptosis via a caspase-dependent pathway. The TGF-ß/Smad pathway also mediated the inhibition of HSFs proliferation and HSFs differentiation into myofibroblasts. Therefore, PD is a potential therapeutic agent for HSs and other fibrotic diseases.


Assuntos
Cicatriz Hipertrófica , Animais , Humanos , Coelhos , Cicatriz Hipertrófica/patologia , Metaloproteinase 2 da Matriz/metabolismo , Caspases/metabolismo , Caspases/farmacologia , Caspases/uso terapêutico , Fibroblastos , Apoptose , Proliferação de Células , Fator de Crescimento Transformador beta/metabolismo
9.
BMC Med Res Methodol ; 22(1): 337, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36577950

RESUMO

BACKGROUND: Estimating the average effect of a treatment, exposure, or intervention on health outcomes is a primary aim of many medical studies. However, unbalanced covariates between groups can lead to confounding bias when using observational data to estimate the average treatment effect (ATE). In this study, we proposed an estimator to correct confounding bias and provide multiple protection for estimation consistency. METHODS: With reference to the kernel function-based double-index propensity score (Ker.DiPS) estimator, we proposed the artificial neural network-based multi-index propensity score (ANN.MiPS) estimator. The ANN.MiPS estimator employed the artificial neural network to estimate the MiPS that combines the information from multiple candidate models for propensity score and outcome regression. A Monte Carlo simulation study was designed to evaluate the performance of the proposed ANN.MiPS estimator. Furthermore, we applied our estimator to real data to discuss its practicability. RESULTS: The simulation study showed the bias of the ANN.MiPS estimators is very small and the standard error is similar if any one of the candidate models is correctly specified under all evaluated sample sizes, treatment rates, and covariate types. Compared to the kernel function-based estimator, the ANN.MiPS estimator usually yields smaller standard error when the correct model is incorporated in the estimator. The empirical study indicated the point estimation for ATE and its bootstrap standard error of the ANN.MiPS estimator is stable under different model specifications. CONCLUSIONS: The proposed estimator extended the combination of information from two models to multiple models and achieved multiply robust estimation for ATE. Extra efficiency was gained by our estimator compared to the kernel-based estimator. The proposed estimator provided a novel approach for estimating the causal effects in observational studies.


Assuntos
Algoritmos , Modelos Estatísticos , Humanos , Pontuação de Propensão , Simulação por Computador , Redes Neurais de Computação
10.
Chem Biodivers ; 19(6): e202200207, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35419971

RESUMO

Two new austocystin analogs, austocystin P (1) and austocystin Q (2), along with fourteen known compounds (3-16) were isolated from the fermentation extract of Aspergillus sp. WHUF05236. The planar structures of 1 and 2 were elucidated through 1D, 2D NMR and MS analyses. Their absolute configurations were determined by the time-dependent density functional (TDDFT)-ECD calculation. Compounds 3, 11, and 12 exhibited antimicrobial activities against Helicobacter pylori with MIC values ranging from 20.00 to 43.47 µM. Compounds 3, 6, and 7 showed cytotoxicities against the human colon cancer cell lines Hct-116 with IC50 values of 101.79, 65.46, and 36.72 µM, respectively.


Assuntos
Aspergillus , Fungos , Aspergillus/química , Fungos/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
11.
BMC Pulm Med ; 21(1): 342, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727907

RESUMO

OBJECTIVE: Little is known concerning the stability of the lower airway microbiome. We have compared the microbiota identified by repeated bronchoscopy in healthy subjects and patients with ostructive lung diseaseases (OLD). METHODS: 21 healthy controls and 41 patients with OLD completed two bronchoscopies. In addition to negative controls (NCS) and oral wash (OW) samples, we gathered protected bronchoalveolar lavage in two fractions (PBAL1 and PBAL2) and protected specimen brushes (PSB). After DNA extraction, we amplified the V3V4 region of the 16S rRNA gene, and performed paired-end sequencing (Illumina MiSeq). Initial bioinformatic processing was carried out in the QIIME-2 pipeline, identifying amplicon sequence variants (ASVs) with the DADA2 algorithm. Potentially contaminating ASVs were identified and removed using the decontam package in R and the sequenced NCS. RESULTS: A final table of 551 ASVs consisted of 19 × 106 sequences. Alpha diversity was lower in the second exam for OW samples, and borderline lower for PBAL1, with larger differences in subjects not having received intercurrent antibiotics. Permutational tests of beta diversity indicated that within-individual changes were significantly lower than between-individual changes. A non-parametric trend test showed that differences in composition between the two exams (beta diversity) were largest in the PSBs, and that these differences followed a pattern of PSB > PBAL2 > PBAL1 > OW. Time between procedures was not associated with increased diversity. CONCLUSION: The airways microbiota varied between examinations. However, there is compositional microbiota stability within a person, beyond that of chance, supporting the notion of a transient airways microbiota with a possibly more stable individual core microbiome.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Pneumopatias Obstrutivas/microbiologia , Microbiota , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Lavagem Broncoalveolar , Broncoscopia , Classificação , Humanos , Pneumopatias Obstrutivas/tratamento farmacológico , Masculino , Microbiota/efeitos dos fármacos , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
12.
J Healthc Eng ; 2021: 9174055, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707800

RESUMO

BACKGROUND: Breast cancer (BRCA) is one of the most common cancers and the leading cause of cancer-related death in women. RNA-binding proteins (RBPs) play an important role in the emergence and pathogenesis of tumors. The target RNAs of RBPs are very diverse; in addition to binding to mRNA, RBPs also bind to noncoding RNA. Noncoding RNA can cause secondary structures that can bind to RBPs and regulate multiple processes such as splicing, RNA modification, protein localization, and chromosomes remodeling, which can lead to tumor initiation, progression, and invasion. METHODS: (1) BRCA data were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases and were used as training and testing datasets, respectively. (2) The prognostic RBPs-related genes were screened according to the overlapping differentially expressed genes (DEGs) from the TCGA database. (3) Univariate Cox proportional hazard regression was performed to identify the genes with significant prognostic value. (4) Further, we used the LASSO regression to construct a prognostic signature and validated the signature in the TCGA and ICGC cohort. (5) Besides, we also performed prognostic analysis, expression level verification, immune cell correlation analysis, and drug correlation analysis of the genes in the model. RESULTS: Four genes (MRPL13, IGF2BP1, BRCA1, and MAEL) were identified as prognostic gene signatures. The prognostic model has been validated in the TCGA and ICGC cohorts. The risk score calculated with four genes signatures could largely predict overall survival for 1, 3, and 5 years in patients with BRCA. The calibration plot demonstrated outstanding consistency between the prediction and actual observation. The findings of online database verification revealed that these four genes were significantly highly expressed in tumors. Also, we observed their significant correlations with some immune cells and also potential correlations with some drugs. CONCLUSION: We constructed a 4-RBPs-based prognostic signature to predict the prognosis of BRCA patients, and it has the potential for treating and diagnosing BRCA.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , Prognóstico , RNA Mensageiro , Proteínas de Ligação a RNA/genética
13.
Chem Biodivers ; 18(7): e2100229, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34085751

RESUMO

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1-11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Penicillium/química , Rhizophoraceae/microbiologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Staphylococcus aureus/efeitos dos fármacos
14.
Curr Opin Biotechnol ; 67: 184-191, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33592536

RESUMO

Ability to directly sequence DNA from the environment permanently changed microbial ecology. Here, we review the new insights to microbial life gleaned from the applications of metagenomics, as well as the extensive set of analytical tools that facilitate exploration of diversity and function of complex microbial communities. While metagenomics is shaping our understanding of microbial functions in ecosystems via gene-centric and genome-centric methods, annotating functions, metagenome assembly and binning in heterogeneous samples remains challenging. Development of new analysis and sequencing platforms generating high-throughput long-read sequences and functional screening opportunities will aid in harnessing metagenomes to increase our understanding of microbial taxonomy, function, ecology, and evolution in the environment.


Assuntos
Metagenômica , Microbiota , Ecologia , Sequenciamento de Nucleotídeos em Larga Escala , Metagenoma/genética , Microbiota/genética , Análise de Sequência de DNA
15.
Mar Drugs ; 18(11)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233743

RESUMO

Deep-sea fungi have become a new arsenal for the discovery of leading compounds. Here five new ophiobolins 1-5, together with six known analogues 6-11, obtained from a deep-sea derived fungus WHU0154. Their structures were determined by analyses of IR, HR-ESI-MS, and NMR spectra, along with experimental and calculated electronic circular dichroism (ECD) analysis. Pharmacological studies showed that compounds 4 and 6 exhibited obvious inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine macrophage RAW264.7 cells. Mechanical study revealed that compound 6 could inhibit the inducible nitric oxide synthase (iNOS) level in LPS-stimulated RAW264.7 cells. In addition, compounds 6, 9, and 10 could significantly inhibit the expression of cyclooxygenase 2 (COX 2) in LPS-induced RAW264.7 cells. Preliminary structure-activity relationship (SAR) analyses revealed that the aldehyde group at C-21 and the α, ß-unsaturated ketone functionality at A ring in ophiobolins were vital for their anti-inflammatory effects. Together, the results demonstrated that ophiobolins, especially for compound 6, exhibited strong anti-inflammatory effects and shed light on the discovery of ophiobolins as new anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/farmacologia , Aspergillus/metabolismo , Macrófagos/efeitos dos fármacos , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Sedimentos Geológicos/microbiologia , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Metabolismo Secundário , Sesterterpenos/isolamento & purificação , Relação Estrutura-Atividade
16.
Appl Microbiol Biotechnol ; 104(18): 7971-7978, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700088

RESUMO

Marine fungi are well known for their ability to produce a multitude of natural products and have been proved to be a particularly rich source of drug leads. Here, 20 pyrones and their analogs (1-20), including two new compounds (1 and 6), were obtained from a marine-derived fungus strain of Aspergillus sp. DM94. Their structures were determined by analyses of UV, IR, HR-ESI-MS, and NMR data. The ability to inhibit Helicobacter pylori in vitro was assessed for these isolated compounds. Results showed that the bis-naphtho-γ-pyrones exhibited potent antibacterial activity against both the standard and multidrug-resistant H. pylori strains. Structure-activity relationship (SAR) analysis suggested that the bis-naphtho[2,3-b]pyrones showed better anti-H. pylori activity than a hybrid of naphtho[2,3-b]pyrone and naphtho[1,2-b]pyrone. In addition, the free hydroxyl group of the C-8 position in the lower unit is vital for its anti-H. pylori activity. Importantly, compound 18 showed a synergistic effect in combination with amoxicillin, clarithromycin, or metronidazole, suggesting its potential use to overcome antibiotic resistance of H. pylori. This study shed light on the discovery of new anti-H. pylori agents. KEY POINTS: • New pyrones discovered from a marine-derived fungus Aspergillus sp. DM94. • Bis-naphtho-γ-pyrones showed potent anti-H. pylori activity. • The anti-H. pylori SAR analysis of bis-naphtho-γ-pyrones was discussed. • Bis-naphtho-γ-pyrone 18 showed synergistic effect with clinical antibiotics.


Assuntos
Anti-Infecciosos , Helicobacter pylori , Antibacterianos/farmacologia , Aspergillus , Testes de Sensibilidade Microbiana , Pironas/farmacologia
17.
FEMS Microbiol Ecol ; 96(5)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32301987

RESUMO

Permafrost underlies a large portion of the land in the Northern Hemisphere. It is proposed to be an extreme habitat and home for cold-adaptive microbial communities. Upon thaw permafrost is predicted to exacerbate increasing global temperature trend, where awakening microbes decompose millennia old carbon stocks. Yet our knowledge on composition, functional potential and variance of permafrost microbiome remains limited. In this study, we conducted a deep comparative metagenomic analysis through a 2 m permafrost core from Svalbard, Norway to determine key permafrost microbiome in this climate sensitive island ecosystem. To do so, we developed comparative metagenomics methods on metagenomic-assembled genomes (MAG). We found that community composition in Svalbard soil horizons shifted markedly with depth: the dominant phylum switched from Acidobacteria and Proteobacteria in top soils (active layer) to Actinobacteria, Bacteroidetes, Chloroflexi and Proteobacteria in permafrost layers. Key metabolic potential propagated through permafrost depths revealed aerobic respiration and soil organic matter decomposition as key metabolic traits. We also found that Svalbard MAGs were enriched in genes involved in regulation of ammonium, sulfur and phosphate. Here, we provide a new perspective on how permafrost microbiome is shaped to acquire resources in competitive and limited resource conditions of deep Svalbard soils.


Assuntos
Pergelissolo , Metagenoma , Noruega , Solo , Microbiologia do Solo , Svalbard
18.
Bioinformatics ; 36(11): 3365-3371, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167532

RESUMO

MOTIVATION: Technological advances in meta-transcriptomics have enabled a deeper understanding of the structure and function of microbial communities. 'Total RNA' meta-transcriptomics, sequencing of total reverse transcribed RNA, provides a unique opportunity to investigate both the structure and function of active microbial communities from all three domains of life simultaneously. A major step of this approach is the reconstruction of full-length taxonomic marker genes such as the small subunit ribosomal RNA. However, current tools for this purpose are mainly targeted towards analysis of amplicon and metagenomic data and thus lack the ability to handle the massive and complex datasets typically resulting from total RNA experiments. RESULTS: In this work, we introduce MetaRib, a new tool for reconstructing ribosomal gene sequences from total RNA meta-transcriptomic data. MetaRib is based on the popular rRNA assembly program EMIRGE, together with several improvements. We address the challenge posed by large complex datasets by integrating sub-assembly, dereplication and mapping in an iterative approach, with additional post-processing steps. We applied the method to both simulated and real-world datasets. Our results show that MetaRib can deal with larger datasets and recover more rRNA genes, which achieve around 60 times speedup and higher F1 score compared to EMIRGE in simulated datasets. In the real-world dataset, it shows similar trends but recovers more contigs compared with a previous analysis based on random sub-sampling, while enabling the comparison of individual contig abundances across samples for the first time. AVAILABILITY AND IMPLEMENTATION: The source code of MetaRib is freely available at https://github.com/yxxue/MetaRib. CONTACT: yaxin.xue@uib.no or Inge.Jonassen@uib.no. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Software , Transcriptoma , Biologia Computacional , Metagenoma , Ribossomos
19.
Microbiol Resour Announc ; 8(27)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270193

RESUMO

Permafrost contains one of the least known soil microbiomes, where microbial populations reside in an ice-locked environment. Here, 56 prokaryotic metagenome-assembled genome (MAG) sequences from 13 phyla are reported. These MAGs will provide information on metabolic pathways that could mediate biogeochemical cycles in Svalbard permafrost.

20.
J Cell Biol ; 218(1): 97-111, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30404948

RESUMO

Mitochondrial function is closely linked to its dynamic membrane ultrastructure. The mitochondrial inner membrane (MIM) can form extensive membrane invaginations known as cristae, which contain the respiratory chain and ATP synthase for oxidative phosphorylation. The molecular mechanisms regulating mitochondrial ultrastructure remain poorly understood. The Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of diverse cellular processes related to membrane remodeling and dynamics. Whether BAR domain proteins are involved in sculpting membranes in specific submitochondrial compartments is largely unknown. In this study, we report FAM92A1 as a novel BAR domain protein localizes to the matrix side of the MIM. Loss of FAM92A1 caused a severe disruption to mitochondrial morphology and ultrastructure, impairing organelle bioenergetics. Furthermore, FAM92A1 displayed a membrane-remodeling activity in vitro, inducing a high degree of membrane curvature. Collectively, our findings uncover a role for a BAR domain protein as a critical organizer of the mitochondrial ultrastructure that is indispensable for mitochondrial function.


Assuntos
Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Proteínas/genética , Linhagem Celular Tumoral , Proliferação de Células , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Microscopia de Fluorescência , Mitocôndrias/ultraestrutura , Membranas Mitocondriais/ultraestrutura , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Osteoblastos/metabolismo , Osteoblastos/ultraestrutura , Fosforilação Oxidativa , Domínios Proteicos , Proteínas/antagonistas & inibidores , Proteínas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
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