RESUMO
BACKGROUND: Gout is a hyperuricemia (HUA)-related inflammatory reaction in the joints. Leech therapy has been effective in the gout, but the exact mechanism is unclear. OBJECTIVES: In this study, an exploration of the therapeutic mechanism of leech therapy in HUA and gouty arthritis (GA) rats was done. MATERIAL AND METHODS: HUA and GA construction utilizing sodium urate crystal, the potassium form of oxygen oxazine acid, and adenine. Serum and tissues were collected to measure uric acid (UA), creatinine (Cr), and urea nitrogen (UN). Enzyme linked immunosorbent assay was executed to evaluate the levels of xanthine oxidase (XOD), interleukin-6 (IL-6)and tumor necrosis factor α (TNF-α). The expression of glucose transporter 9 (GLUT9), organic anion transporter 3 (OAT3), adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) and the nuclear factor kappa B (NF-kB), interleukin-1ß (IL-1ß), Toll-like Receptor 2 (TLR2) were assessed by Western blot and visualized in immunohistochemistry staining. RESULTS: Leech therapy reduces the levels of UA, Cr, and UN as well as the liver and serum levels of XOD activity, increasing the expressions of GLUT9, ABCG2, and OAT3 in the kidney. Meanwhile, it reduces joint swelling and lowers the levels of TNF-α, IL-6, IL-1ß, TLR2, and NF-kB. CONCLUSIONS: Leech therapy regulates the metabolism of uric acid and treats gouty arthritis with an anti-inflammatory effect.
RESUMO
Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.
Assuntos
Alginatos , Antibacterianos , Proteína Morfogenética Óssea 2 , Regeneração Óssea , Gelatina , Microesferas , Gelatina/química , Gelatina/farmacologia , Alginatos/química , Alginatos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/química , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Liberação Controlada de FármacosRESUMO
Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.
Assuntos
Antineoplásicos , Receptores Frizzled , Neoplasias , Via de Sinalização Wnt , Humanos , Receptores Frizzled/metabolismo , Receptores Frizzled/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Terapia de Alvo Molecular/métodosRESUMO
Two novel Gram-stain-negative, aerobic, non-motile and rod-shaped bacteria, designated as WL0004T and XHP0148T, were isolated from seawater samples collected from the coastal areas of Nantong and Lianyungang, PR China, respectively. Both strains were found to grow at 10-42â°C (optimum, 37â°C) and with 2.0-5.0â% (w/v) NaCl (optimum, 3.0â%). Strain WL0004T grew at pH 6.0-9.0 (optimum, pH 7.0-8.0), while XHP0148T grew at pH 6.0-10.0 (optimum, pH 7.0-8.0). The major cellular fatty acids (>10â%) of both strains included summed feature 8 (C18â:â1 ω6c and/or C18â:â1 ω7c). In addition, strain WL0004T contained 11-methyl C18â:â1 ω7c and strain XHP0148T contained C12â:â0 3-OH. The respiratory quinone of both strains was ubiquinone-10. The G+C content of genomic DNA of strains WL0004T and XHP0148T were 62.5 and 63.0âmol%, respectively. Strains WL0004T and XHP0148T showed the highest 16S rRNA gene sequence similarity to Ruegeria pomeroyi DSS-3T (99.4 and 99.0â%, respectively), and the 16S rRNA gene-based phylogenetic analysis indicated that the two strains were closely related to members of the genus Ruegeria. The average nucleotide identity and digital DNA-DNA hybridization values among the two strains and type strains of the genus Ruegeria were all below 95 and 70â%, respectively, and the phylogenetic tree reconstructed from the bac120 gene set indicated that the two strains are distinct from each other and the members of the genus Ruegeria. Based on this phenotypic and genotypic characterization, strains WL0004T (=MCCC 1K07523T=JCM 35565T=GDMCC 1.3083T) and XHP0148T (=MCCC 1K07543T=JCM 35569T=GDMCC 1.3089T) should be recognized as representing two novel species of the genus Ruegeria and the names Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov. are proposed, respectively.
Assuntos
Ácidos Graxos , Água do Mar , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem BacterianaRESUMO
Intracortical brain-computer interfaces offer superior spatial and temporal resolutions, but face challenges as the increasing number of recording channels introduces high amounts of data to be transferred. This requires power-hungry data serialization and telemetry, leading to potential tissue damage risks. To address this challenge, this paper introduces an event-based neural compressive telemetry (NCT) consisting of 8 channel-rotating Δ-ADCs, an event-driven serializer supporting a proposed ternary address event representation protocol, and an event-based LVDS driver. Leveraging a high sparsity of extracellular spikes and high spatial correlation of the high-density recordings, the proposed NCT achieves a compression ratio of >11.4×, while consumes only 1 µW per channel, which is 127× more efficient than state of the art. The NCT well preserves the spike waveform fidelity, and has a low normalized RMS error <23% even with a spike amplitude down to only 31 µV.
RESUMO
Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.
RESUMO
Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 µg/g) were significantly greater compared to the LF group (0.02 ± 0.01 µg/g, P < 0.001) and GD group (0.37 ± 0.11 µg/g, P < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 µg/g) compared to the LF group (0.01 ± 0.00 µg/g, P < 0.001) and GD group (0.06 ± 0.02 µg/g, P = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group. Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.
RESUMO
Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions.
Assuntos
MicroRNAs , Pequeno RNA não Traduzido , Humanos , Lipopolissacarídeos/farmacologia , RNA de Transferência/genética , RNA de Transferência/metabolismo , MicroRNAs/genética , Pequeno RNA não Traduzido/metabolismo , Análise em Microsséries , Inflamação/tratamento farmacológico , Inflamação/genéticaRESUMO
Superelastic alloys used for stents, biomedical implants, and solid-state cooling devices rely on their reversible stress-induced martensitic transformations. These applications require the alloy to sustain high deformability over millions of cycles without failure. Here, we report an alloy capable of enduring 10×10^{7} tensile stress-induced phase transformations while still exhibiting over 2% recoverable elastic strains. After millions of cycles, the alloy is highly reversible with zero stress hysteresis. We show that the major martensite variant is reversible even after multimillions of cycles under tensile loadings with a highly coherent (11[over ¯]0)_{A} interface. This discovery provides new insights into martensitic transformation, and may guide the development of superelastic alloys for multimillion cycling applications.
RESUMO
Elastocaloric cooling has emerged as an eco-friendly technology capable of eliminating greenhouse-gas refrigerants. However, its development is limited by the large driving force and low efficiency in uniaxial loading modes. Here, we present a low-force and energy-efficient elastocaloric air cooling approach based on coil-bending of NiTi ribbons/wires. Our air cooler achieves continuous cold outlet air with a temperature drop of 10.6 K and a specific cooling power of 2.5 W g-1 at a low specific driving force of 26 N g-1. Notably, the cooler shows a system coefficient of performance of 3.7 (ratio of cooling power to rotational mechanical power). These values are realized by the large specific heat transfer area (12.6 cm2 g-1) and the constant cold zone of NiTi wires. Our coil-bending system exhibits a competitive performance among caloric air coolers.
RESUMO
Normalizing inï¬amed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inï¬ammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inï¬amed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.
RESUMO
A Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped, catalase-positive, strictly aerobic marine bacterium, designated XHP0103T, was isolated from seawater collected from the southern Yellow Sea, PR China (34° 45' 53â³ N 119° 25' 30â³ E). Strain XHP0103T grew optimally at 28â°C, pH 7.5 and in 1.0-3.0â% (w/v) sea salt. MK-6 was the major respiratory quinone. The major cellular fatty acids (>10%) were iso-C15â:â0, iso-C15â:â1 G and iso-C17â:â0 3-OH. The polar lipid profile contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. Results of 16S rRNA gene sequence analysis indicated that strain XHP0103T displayed highest sequence similarity to Aestuariibaculum marinum IP7T (94.1â%). However, the phylogenetic trees based on 16S rRNA gene sequences suggested that strain XHP0103T clustered with Tamlana crocina HST1-43T (93.4â% sequence similarity) and Aestuariivivens insulae AH-MY3T (93.5â%). Genome sequencing revealed that strain XHP0103T comprised 3â134â388 bp with 2770 protein-coding genes, and the DNA G+C content was 35.5 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain XHP0103T and T. crocina HST1-43T were 73.6 and 17.3â%, respectively. Based on phylogenetic, phenotypic, genomic and chemotaxonomic evidence, strain XHP0103T represents a novel genus in the family Flavobacteriaceae, for which the name Marixanthotalea marina gen. nov., sp. nov. is proposed. The type strain is XHP0103T (=MCCC 1K06060T=JCM 34682T).
Assuntos
Ácidos Graxos , Flavobacteriaceae , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Análise de Sequência de DNA , Composição de Bases , Técnicas de Tipagem Bacteriana , Água do Mar/microbiologiaRESUMO
The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aß42/Aß40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aß42/Aß40 levels (r = -0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aß-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance.
Assuntos
Imagem de Tensor de Difusão , Privação do Sono , Humanos , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagem , Vigília , Descanso , Imageamento por Ressonância Magnética , Substância Cinzenta/diagnóstico por imagemRESUMO
This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.
Assuntos
Ferroptose , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Animais , Ratos , Ferroptose/genética , Glucose , Glutationa , Ferro , Traumatismo por Reperfusão Miocárdica/genética , Miócitos Cardíacos , Oxigênio , Espécies Reativas de Oxigênio , RNA Mensageiro/genéticaRESUMO
Carbon dots (CDs) have emerged as potential biomaterials for bioimaging and antimicrobial applications. However, the lack of tunable long-wavelength emission performance and imprecise antibacterial mechanism limit their practical application. Thus, developing versatile CDs that combine outstanding optical performance and excellent antibacterial activity is of great practical significance. Herein, we prepared a novel nitrogen and fluorine co-doped CDs (N, F-CDs) from o-phenylenediamine and 2,3,5,6-tetrafluoroterephthalic acid, which exhibit high fluorescence quantum yield of 52.2%, large Stokes shift of 112 nm, as well tunable multicolor emission light from blue to red region. Thanks to the high biocompatibility and excellent photostability, the N, F-CDs were successfully implemented to multicolor biolabeling of mammalian cells, protozoan cells and plant cells. Moreover, the negatively charged N, F-CDs hold inherent efficient antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). By thoroughly studying the underlying antibacterial mechanisms at the molecular level through real-time quantitative PCR assay, we found the expression of related genes was notably down-regulated, further demonstrated that N, F-CDs against two bacterial strains had distinct target pathways. Our work provides a new reference for developing highly fluorescent multicolor CDs, and may facilitate the design and application of CDs-based nanomaterials in biological environment.
Assuntos
Escherichia coli , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis , Carbono , Corantes , MamíferosRESUMO
Haemoglobin E (HbE) ß-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE ß-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid â AAG; lysine, E26K), and any mutation causing severe ß-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (ß-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations.
Assuntos
Hemoglobina E , Talassemia , Talassemia beta , Humanos , Animais , Camundongos , Talassemia beta/genética , Hemoglobina E/genética , Talassemia/genética , Mutação , Mutação PuntualRESUMO
A Gram-stain-negative, aerobic, non-motile and rod-shaped strain, designated LJY008T, was isolated from the intestinal of Eriocheir sinensis in Pukou base of Jiangsu Institute of Freshwater Fisheries. Strain LJY008T could grow at 4-37 â (optimum, 30 â), pH 6.0-8.0 (optimum, pH 7.0), and with 1.0-6.0% NaCl (w/v; optimum, 1.0%). Strain LJY008T shared highest 16S rRNA gene sequence similarity with Jinshanibacter zhutongyuii CF-458T (99.3%), followed by J. allomyrinae BWR-B9T (99.2%), Insectihabitans xujianqingii CF-1111T (97.3%), and Limnobaculum parvum HYN0051T (96.7%). The major polar lipids include phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The only respiratory quinone was Q8, and the main fatty acids (> 10%) were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c), and C14:0. The genome-based phylogenies showed that strain LJY008T was closely associated with members of the genus Jinshanibacter, Insectihabitans, and Limnobaculum. The average nucleotide identities and average amino acid identities (AAI) among strain LJY008T and closely related neighbours were all below 95%, and the digital DNA-DNA hybridization values among them were all below 36%. The genomic DNA G + C content of strain LJY008T was 46.1%. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain LJY008T represents a novel species of the genus Limnobaculum, for which the name Limnobaculum eriocheiris sp. nov. is proposed. The type strain is LJY008T (= JCM 34675T = GDMCC 1.2436T = MCCC 1K06016T). In addition, the genera Jinshanibacter and Insectihabitans were reclassified as Limnobaculum, because there was no significant genome-scale divergence or diagnosable difference on phenotypic and chemotaxonomic traits, such as strains of Jinshanibacter and Insectihabitans sharing AAI values of 93.88-94.96%.
Assuntos
Fosfolipídeos , Ubiquinona , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Ubiquinona/química , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Ácidos Graxos/análise , Análise de Sequência de DNARESUMO
Gastric cancer is a tumor type characterized by lymph node metastasis and the invasion of local tissues. There is thus a critical need to clarify the molecular mechanisms governing gastric cancer onset and progression to guide the treatment of this disease. Long non-coding RNAs and mRNA expression profiles associated with early and local advanced gastric cancer were examined through microarray analyses, with GO and KEGG analyses being employed as a means of exploring the functional roles of those long non-coding RNAs and mRNAs that were differentially expressed in gastric cancer. In total, 1005 and 1831 lncRNAs and mRNAs, respectively, were found to be differentially expressed between early and local advanced gastric cancer. GO and KEGG analyses revealed several pathways and processes that were dysregulated, including the RNA transport, ECM-receptor interaction, and mRNA splicing pathways. In co-expression networks, E2F1, E2F4, and STAT2 were identified as key transcriptional regulators of these processes. Moreover, thrombospondin-2 was confirmed as being expressed at high levels in more advanced gastric cancer by both the GEO and TCGA databases. RNA-sequencing analyses of SGC-790 cells transfected to express thrombospondin-2 further revealed this gene to enhance NF-kB and TNF pathway signaling activity. These results offer insight into gastric cancer-related regulatory networks and suggest thrombospondin-2 to be an important oncogene that drives the progression of this deadly cancer type.
RESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and its treatment remains a big challenge. The pathogenesis of PD may be related to environmental and genetic factors, and exposure to toxins and gene mutations may be the beginning of brain lesions. The identified mechanisms of PD include α-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, neuroinflammation, and gut dysbiosis. The interactions among these molecular mechanisms complicate the pathogenesis of PD and pose great challenges to drug development. At the same time, the diagnosis and detection of PD are also one of obstacles to the treatment of PD due to its long latency and complex mechanism. Most conventional therapeutic interventions for PD possess limited effects and have serious side effects, heightening the need to develop novel treatments for this disease. In this review, we systematically summarized the pathogenesis, especially the molecular mechanisms of PD, the classical research models, clinical diagnostic criteria, and the reported drug therapy strategies, as well as the newly reported drug candidates in clinical trials. We also shed light on the components derived from medicinal plants that are newly identified for their effects in PD treatment, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for PD therapy.
Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Estresse Oxidativo , Mutação , Transdução de SinaisRESUMO
A Gram-staining-positive, non-motile, aerobic, spherical actinobacterium, designated WL0053T, was isolated from the coastal sediment of Nantong City, Jiangsu Province, China. The 16S rRNA gene sequence of strain WL0053T exhibited the highest similarities to Nocardioides mesophilus MSL-22T (98.0%), N. massiliensis GD12T (97.8%), Marmoricola bigeumensis MSL-05T (97.6%), and N. jensenii DSM 20641T (97.3%). The polyphasic taxonomic approach was used for the identification of strain WL0053T. This strain formed white, round, and smooth colonies and grew in the presence of 0-18% (w/v) NaCl (optimum, 0-4.0%), at pH 6.0-9.0 (optimum, pH 7.0) and at 20-37 °C (optimum, 28 °C). The main cellular fatty acids comprised of C17:1 ω8c, C18:1 ω9c, and iso-C16:0. The genomic DNA G + C content was 71.9%. The predominant quinone was MK-8(H4), and the major polar lipid consisted of phosphatidylcholine, glycolipid, phosphatidylethanolamine, and two unidentified phospholipids. Phylogenetic trees of 16S rRNA gene and bac120 gene set indicted that strain WL0053T was closely related to the species N. iriomotensis and N. mesophilus, while these two species clustered in a separate clade together with M. caldifontis YIM 730233T in the bac120 tree. Combined with the analysis of average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH), it can be considered that the strain WL0053T is a new member of the genus Nocardioides and is proposed to be named as Nocardioides jiangsuensis sp. nov.. The type strain is WL0053T (=MCCC 1K05897T=JCM 34671T=GDMCC 4.192T). Furthermore, based on the fact that the genera Nocardioides and Marmoricola both appeared polyphyletic with no significant difference on phenotypic and chemotaxonomic traits, we proposed to reclassify the genus Marmoricola as Nocardioides.