RÉSUMÉ
Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.
Sujet(s)
Agammaglobulinaemia tyrosine kinase , Encéphalopathie ischémique , Substance blanche , Animaux , Mâle , Souris , Agammaglobulinaemia tyrosine kinase/antagonistes et inhibiteurs , Agammaglobulinaemia tyrosine kinase/métabolisme , Encéphalopathie ischémique/traitement médicamenteux , Encéphalopathie ischémique/anatomopathologie , Encéphalopathie ischémique/métabolisme , Maladie chronique , Souris de lignée C57BL , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Microglie/anatomopathologie , Maladies neuro-inflammatoires/traitement médicamenteux , Maladies neuro-inflammatoires/métabolisme , Maladies neuro-inflammatoires/anatomopathologie , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/usage thérapeutique , Substance blanche/effets des médicaments et des substances chimiques , Substance blanche/anatomopathologie , Substance blanche/métabolismeRÉSUMÉ
BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.
Sujet(s)
Étude d'association pangénomique , Accident vasculaire cérébral ischémique , Analyse de randomisation mendélienne , Humains , Accident vasculaire cérébral ischémique/génétique , Accident vasculaire cérébral ischémique/physiopathologie , Protéine-2 associée à la multirésistance aux médicaments , Locus de caractère quantitatif , Mâle , Femelle , Sujet âgé , Récupération fonctionnelle , Adulte d'âge moyen , Résultat thérapeutique , Phénotype , État fonctionnelRÉSUMÉ
Background: Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear. Methods: Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed. Results: MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04). Conclusions: This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.
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Sclérose en plaques , Humains , Sclérose en plaques/génétique , Acuité des besoins du patient , Lymphocytes T CD8+ , Causalité , Numération cellulaireRÉSUMÉ
Astrocytes are a heterogenous group of macroglia present in all regions of the brain and play critical roles in many aspects of brain development, function and disease. Previous studies suggest that the B-cell lymphoma-2 associated X protein (BAX)-dependent apoptosis plays essential roles in regulating neuronal number and achieving optimal excitation/inhibition ratio. The aim of the present paper was to study whether BAX regulates astrocyte distribution in a region-specific manner. Immunofluorescence staining of SOX9 was used to analyze and compare astrocyte density in primary somatosensory cortex, motor cortex, retrosplenial cortex and hippocampus in heterozygous and homozygous BAX knockout mice at age of six weeks when cortical development has finished and glia development has reached a relatively steady state. The results showed that astrocyte density varied significantly among different cortical subdivisions and between cortex and hippocampus. In contrast to the significant increase in GABAergic interneurons, the overall and region-specific astrocyte density remained unchanged in the cortex when BAX was absent. Interestingly, a significant reduction of astrocyte density was observed in the hippocampus of BAX knockout mice. These data suggest that BAX differentially regulates neurons and astrocytes in cortex as well as astrocytes in different brain regions during development. This study provided important information about the regional heterogeneity of astrocyte distribution and the potential contribution of BAX gene during development.
Sujet(s)
Astrocytes , Hippocampe , Animaux , Interneurones , Souris , Neurones , Protéine Bax/génétiqueRÉSUMÉ
OBJECTIVE: Experiments were performed to evaluate CYLD expression in human gingival tissue samples and to examine the effects of CYLD on inflammatory responses in lipopolysaccharide (LPS)- or TNF-α-stimulated human gingival fibroblasts (HGFs). METHODS: Immunohistochemistry for CYLD and p65 expression was performed with healthy and inflamed gingival tissue samples. siRNA was used to knock down the expression of CYLD in HGFs. Upon LPS or TNF-α stimulation, NF-κB activation was detected in control and CYLD-knockdown HGFs. RT-PCR was applied to determine gene expression. Western blot analyses were employed to assess protein expression. Immunofluorescence staining was carried out to evaluate the nuclear translocation of p65. RESULTS: Immunohistochemical staining showed the expression of CYLD in human gingival tissues. In addition, CYLD protein expression was reduced in inflamed gingival tissue samples compared with healthy tissue samples. CYLD knockdown greatly enhanced the mRNA expression of proinflammatory cytokines in LPS- or TNF-α-stimulated HGFs. Furthermore, knocking down CYLD expression increased LPS-stimulated NF-κB activation in HGFs. Unexpectedly, CYLD knockdown did not affect TNF-α-induced NF-κB activation. CONCLUSIONS: Our results suggest that CYLD participates in periodontal inflammatory responses by negatively regulating LPS-induced NF-κB signalling.
Sujet(s)
Deubiquitinating enzyme CYLD , Fibroblastes , Gencive , Cellules cultivées , Enzymes de désubiquitinylation , Humains , Lipopolysaccharides , Facteur de transcription NF-kappa BRÉSUMÉ
Development of drug products from natural sources enable advantageous treatment and therapy options. Bioactive compounds in Ganoderma lucidum spore powder (GLSP) are known for vast antibacterial, antioxidant and anti-cancer properties. Herein, we studied the use of dual-probe ultrasound to extract triterpenoids from GLSP and further investigated the bioactivity of resulting products. FTIR results confirm the presence of key peaks although dual-probe ultrasound varied extraction efficacy. Response surface methodology (RSM) was used to optimize extraction conditions (55:28 for solvent to solid ratio, 10.38 s of ultrasound time and 94% v/v of ethanol concentration). HPLC-Q-TOF-MS confirmed the presence of nine different compounds and in vitro tests confirm good biocompatibility. Extracts are shown to inhibit DPPH radicals, reaching a maximum (61.09 ± 1.38%) at triterpenoid concentrations of 600 µg/mL. Dual-mode assisted extraction provides an enhanced approach for active embedded fiber production on a scale favorable to industry when using optimized process parameters. Furthermore, triterpenoid extracts show antibacterial properties on Staphylococcus aureus and Escherichia coli with potential in antibacterial and anticancer applications.
Sujet(s)
Reishi , Triterpènes , Poudres , Sonication/méthodes , SporesRÉSUMÉ
Improving the proliferation of probiotics (ca. Bifidobacterium) and inhibiting the growth of pathogenic bacteria (ca. Escherichia coli) is crucial for human health. This study demonstrates the fabrication of core-shell structure fibers using electrohydrodynamic 3D printing to help improve gastrointestinal tract microbial content. These fibers have various geometries and are capable of encapsulating stachyose into cellulose acetate (shell layer) and loading proteoglycan into polyacrylic resin II (core layer). The impact of membrane geometry on drug release behavior and the effect of exchanging the loading site on physicochemical properties of the resulting fibers were studied. The printed fibrous membranes possess a biphasic drug release profile in simulated intestinal fluid with a burst release within the first 12 h and a slower sustained release up to 72 h. The speed order priority for drug release rate of the printed membrane was whole-circle > semi-circle > square. Moreover, the membranes exhibit good biocompatibility on L929 cells and excellent improvement effects on Bifidobacterium bifidum, combining inhibition effects on Escherichia coli. In summary, the dual-drug fibrous membranes presented here and their precision-fabricated patterns pave a new direction for improving the gastrointestinal tract microbial ecosystem health in the human body.
Sujet(s)
Vecteurs de médicaments/composition chimique , Impression tridimensionnelle , Probiotiques/composition chimique , Résines acryliques/composition chimique , Animaux , Bifidobacterium/croissance et développement , Bifidobacterium/physiologie , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Lignée cellulaire , Survie cellulaire/effets des médicaments et des substances chimiques , Cellulose/analogues et dérivés , Cellulose/composition chimique , Libération de médicament , Tube digestif/microbiologie , Souris , Oligosaccharides/composition chimique , Probiotiques/métabolisme , Protéoglycanes/composition chimiqueRÉSUMÉ
When ingested as a dietary supplement, Ganoderma lucidum spore powders (GLSP) provide various health benefits such as enhanced immunity, liver protection and anti-cancer effects. In this study, triterpenoid extraction from GLSP was achieved using an ultrasound-assisted process which was optimized using response surface methodology (RSM). Ultrasound-assisted extraction (UAE) was also compared to the most conventional chemical extraction method. For UAE, optimum extraction conditions were found to be ethanol concentration = 95% v/v; solvent to solid ratio = 50:1 mL/g; ultrasound time = 5.4 min; ultrasound power = 564.7 w, and ultrasound probe distance = 8.2 cm. At optimal UAE conditions, no significant differences were found between experimental (0.97 ± 0.04 %) and predicted values (99%); which indicates appreciable correlation at the 97% confidence interval. The findings show the application of Box-Behnken design (BBD) to predict and optimize triterpenoid yield for UAE of triterpenoid from GLSP. Furthermore, glucose consumption was 2.68 times that of control samples when tested with insulin-resistant HepG2 cell, showing potential use in type 2 diabetes. In addition, triterpenoid extracts show good biocompatibility and inhibition of antioxidant activity.
Sujet(s)
Reishi/composition chimique , Spores fongiques/composition chimique , Triterpènes , Ondes ultrasonores , Triterpènes/composition chimique , Triterpènes/isolement et purificationRÉSUMÉ
The apoptosis of human periodontal ligament cells (HPDLCs) may be an important factor of the negative effect of advanced glycation end products (AGEs) on the periodontal tissue of diabetic patients. However, the pathways or potential effects of apoptosis in AGEs-treated HPDLCs have not been fully elucidated. Autophagy is closely related to apoptosis. Herein, we investigated the potential mechanism of apoptosis and autophagy in HPDLCs treated with AGEs via an in vitro model. We found that AGEs-treated HPDLCs showed a time- and concentration-dependent reduction in the cell survival rate. The mitochondrial-dependent apoptosis was induced in AGEs-treated HPDLCs, as confirmed by the mitochondrial membrane potential depolarization, decreased Bcl-2 expression, increased Bax expression, and increased caspase-3 and PARP cleavage. Autophagy was also induced in AGEs-treated HPDLCs, as indicated by the conversion of LC3-II/LC3-I and the presence of autophagosomes. Interestingly, our study results suggested that apoptosis and autophagy were related to reactive oxygen species (ROS) production. In addition, AGEs-induced autophagy acted as a latent factor in decreasing the generation of ROS in HPDLCs and protecting against the AGEs-induced apoptosis. In summary, our study shows that ROS are essential in AGEs-induced HPDLCs apoptosis and autophagy, which may be a molecular mechanism for the repairment of ROS-induced damage in HPDLCs treated with AGEs to promote cell survival. The present study might provide new insights into the therapeutic targeting of HPDLCs autophagy, which could be an additional strategy for periodontitis in patients with diabetes mellitus.
RÉSUMÉ
OBJECTIVE: Macrophages could be fully polarized and acquire specific phenotype like M1, which considered to be essential for the alveolar bone destruction during the development of periodontitis. However, the molecular mechanisms underlying the effects of M1 macrophages on the alveolar bone destruction are still not clear yet. METHODS: Mouse periodontitis model was established to determine the involvement of M1 macrophages in the pathogenic process. Condition medium of the M1 macrophages (M1-CM) was incubated with pre-osteoblasts to evaluate its effects on the osteoblastogenesis. Cells after treatment with CM were used for RNA-sequencing, quantitative PCR, Western blotting, and immunofluorescence staining to figure out pathways involved in the inhibition of osteoblastogenesis. RESULTS: Increased infiltration of M1 macrophages was associated with alveolar bone destruction in periodontitis. M1-CM markedly suppressed the generation of osteoblasts as evidenced by decreased expressions of Runx2 and Ocn, as well as reduced activity of ALP. Interestingly, RNA-sequencing indicated the activation of TLR4/AP1 signaling pathway in pre-osteoblasts treated with CM. Inhibition of TLR4 reduced the translocation of AP1 and rescued the osteoblastogenesis reduced by M1-CM. CONCLUSION: M1 macrophages induce TLR4/AP1 signaling of pre-osteoblasts to inhibit the osteoblastogenesis via paracrine, at least partially contributing to alveolar bone destruction in periodontitis.
Sujet(s)
Résorption alvéolaire , Macrophages/métabolisme , Parodontite , Récepteur de type Toll-4 , Résorption alvéolaire/traitement médicamenteux , Résorption alvéolaire/anatomopathologie , Animaux , Souris , Ostéoblastes , Parodontite/traitement médicamenteux , Parodontite/anatomopathologie , Transduction du signalRÉSUMÉ
Here, we introduce core-shell nanofibers based on chitosan (CS)-loaded poly (ε-caprolactone) (PCL) shell and 5-fluorouracil (5-FU)-loaded Poly(N-vinyl-2-pyrrolidone) (PVP) core for synergistic therapy of melanoma skin cancer. The yielded nanofibers exhibited an average diameter of 503â¯nm with high drug-encapsulating efficiency and good mechanical properties. Moreover, the burst release of 5-FU significantly inhibited melanoma skin cancer cells (B16F10 cells), and the sustained release of CS exhibited "remedying effects" on normal skin cells (L929 cells) after suffering adverse effects from 5-FU treatment. For the B16F10 cells, the early apoptosis cells increased from 0.8% to 62.2% after being treated with blended films loaded with 5-FU (2â¯wt%) for 24â¯h; for the L929 cells, the vital cells increased from 68.9% to 77.0%, and the early apoptosis of stage cells decreased from 12.3% to 10.9% after being treated with blended films with CS (8â¯wt%) for 24â¯h. In conclusion, the results introduced in this work can be a promising strategy for cancer treatment and possesses synergism potential to broaden an avenue for chemotherapeutic therapy with minimum adverse effects on normal cells.
Sujet(s)
Antinéoplasiques/administration et posologie , Chitosane/administration et posologie , Systèmes de délivrance de médicaments , Fluorouracil/administration et posologie , Nanofibres/administration et posologie , Polyesters/administration et posologie , Povidone/administration et posologie , Animaux , Antinéoplasiques/composition chimique , Lignée cellulaire , Prolifération cellulaire/effets des médicaments et des substances chimiques , Chitosane/composition chimique , Libération de médicament , Synergie des médicaments , Fluorouracil/composition chimique , Mélanome expérimental/traitement médicamenteux , Souris , Nanofibres/composition chimique , Polyesters/composition chimique , Povidone/composition chimique , Tumeurs cutanées/traitement médicamenteuxRÉSUMÉ
Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer-associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast-like phenotype of Cal27 cells, induced epithelial-mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy.
Sujet(s)
Fibroblastes associés au cancer/métabolisme , Carcinome épidermoïde/anatomopathologie , Facteurs de transcription de choc thermique/métabolisme , Tumeurs de la bouche/anatomopathologie , Régulation positive , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Animaux , Fibroblastes associés au cancer/transplantation , Carcinome épidermoïde/métabolisme , Mouvement cellulaire , Prolifération cellulaire , Transition épithélio-mésenchymateuse , Femelle , Régulation de l'expression des gènes tumoraux , Humains , Mâle , Souris nude , Adulte d'âge moyen , Tumeurs de la bouche/métabolisme , Stadification tumorale , Transplantation tumorale , Pronostic , Analyse de survie , Microenvironnement tumoralRÉSUMÉ
Inflammation is closely related to oral squamous cell carcinoma (OSCC). However, its mechanism is still obscure. Toll-like receptor 2 (TLR2) plays an important role in oral chronic inflammatory diseases, but the role of TLR2 in OSCC is unclear. Here, we investigated the expression of TLR2 expression in OSCCs and examined the potential role of TLR2 in OSCC through its association with clinicopathological features and patient outcome. We used 4-nitroquinoline 1-oxide (4-NQO) to induce a tongue cancer model in TLR2-/- and wild type (WT) mice. Histological and clinical results both indicated that TLR2 played a protective role in oral tumorigenesis. The results of a cytometric bead array (CBA) indicated that TLR2 deficiency resulted in Th1 and Th2 cytokine abnormalities, especially Th2 abnormalities. Immunohistochemistry also showed that TLR2 deficiency increases the number of tongue-infiltrating M2 macrophages. Overall, our results demonstrated that TLR2 plays an important role in the prevention of oral tumorigenesis and affects the levels of Th2 cytokines and tongue-infiltrating M2 macrophages; therefore, it may be used to prevent the development of oral cancer.
RÉSUMÉ
Chitosan is an extremely valuable biopolymer and is usually obtained as a byproduct from the shells of crustaceans. In the current work, chitosan is obtained from an herbal source (Ganoderma lucidum spore powder (GLSP)) for the first time. To show this, both standard (thermochemical deacetylation, (TCD)) and emerging (ultrasound-assisted deacetylation (USAD)) methods of chitosan preparation were used. The obtained chitosan was characterized by elemental analysis, XRD (X-ray diffraction), FT-IR (Fourier transform infrared spectroscopy) and thermogravimetric measurements. The process resulted in chitosan possessing comparable values of DD, [η] and [Formula: see text] to the commercial product. Chitosan obtained via both processes (TCD and USAD) displayed excellent biocompatibility; although the USAD prepared biopolymer exhibited significantly improved fibroblast (L929 cell) viability and enhanced antibacterial zones for both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The findings of new herbal chitosan mark key developments of natural biomaterials; marking a potential shift from conventional sea-based organisms.
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Chitosane/pharmacologie , Reishi/composition chimique , Spores fongiques/composition chimique , Acétylation , Animaux , Lignée cellulaire , Survie cellulaire/effets des médicaments et des substances chimiques , Chitosane/synthèse chimique , Chitosane/isolement et purification , Escherichia coli/effets des médicaments et des substances chimiques , Escherichia coli/croissance et développement , Fibroblastes/cytologie , Fibroblastes/effets des médicaments et des substances chimiques , Souris , Tests de sensibilité microbienne , Poudres , Sonication , Staphylococcus aureus/effets des médicaments et des substances chimiques , Staphylococcus aureus/croissance et développementRÉSUMÉ
Camellia fangchengensis Liang et Zhong, belonging to the genus Camellia sect. Thea (Theaceae), is an endemic tea species to the south and southwest areas of Guangxi province, People's Republic of China. Known as a wild tea plant, the leaves have been used for producing green tea or black tea by the local people of its growing area. HPLC and LC-MS analysis showed the leaves contain oligomeric catechins as major phenolic components. Further detailed phytochemical study led to the identification of five flavan-3-ol dimers (1-5) including two new ones, fangchengbisflavans A (1) and B (2) from the leaves of C. fangchengensis, together with six known monomers (6-11) and one glucoside (12), in addition to gallic acid (13). Their structures were determined by extensive spectroscopic analysis. Most of the isolates displayed significant antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radical scavenging assays. The results suggested that the leaves of C. fangchengensis, rich in flavan-3-ol oligomers and monomers as potent antioxidants, could be a valuable plant resource for the production of tea and natural beverages.
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Antioxydants/composition chimique , Camellia sinensis/composition chimique , Flavonoïdes/composition chimique , Extraits de plantes/composition chimique , Dimérisation , Structure moléculaire , Feuilles de plante/composition chimiqueRÉSUMÉ
miR-34a is a conserved microRNA highly expressed in the brain. It is thought to play critical roles in regulating many aspects of brain development and function, such as neural stem cell proliferation and differentiation, neuronal migration and apoptosis, fear memory consolidation, etc. However, the assessment of its function was mainly conducted through vector-mediated overexpression and miRNA sponge or antagomir-mediated functional suppression, therefore may suffer from nonspecific off-target effects or incomplete inactivation. We thus analyzed mouse model with a targeted deletion of miR-34a which completely abolishes its expression. To our surprise, loss of miR-34a led to neither an obvious change in brain size, morphology or cortical lamination, nor impaired marker gene expression in major excitatory and inhibitory neuron types in the neocortex. In addition, miR-34a ablation did not affect fear memory formation or consolidation, as well as the anxiety or depression related behavior. However, the performance of mice in rotarod assay was significantly affected, suggesting a defect in motor activity in miR-34a deficient mice. As neocortical parvalbumin (PV) neurons are known for high level miR-34a expression, we also tested the effect of PV-Cre-mediated conditional miR-34a deletion. Similar as germline deletion, PV neuron specific miR-34a deletion did not affect cortical lamination or PV expression in the neocortex. Our studies suggest that, although miR-34a may be involved in regulating certain aspects of brain development or function, such as motor activity, it does not play a significant role in regulating brain morphogenesis, cortical lamination or neocortical neuron subtype specification, and it is also dispensable for fear memory formation, expression and consolidation.
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Encéphale/croissance et développement , microARN/génétique , Animaux , Apoptose , Différenciation cellulaire , Mouvement cellulaire , Prolifération cellulaire , Souris , Souris knockout , Cellules souches neurales , Neurones/métabolisme , Parvalbumines/métabolismeRÉSUMÉ
The crustacean cuticle is a composite material that covers the whole animal and forms the continuous exoskeleton. Nano-fibers composed of chitin and protein molecules form most of the organic matrix of the cuticle that, at the macroscale, is organized in up to eight hierarchical levels. At least two of them, the exo- and endocuticle, contain a mineral phase of mainly Mg-calcite, amorphous calcium carbonate and phosphate. The high number of hierarchical levels and the compositional diversity provide a high degree of freedom for varying the physical, in particular mechanical, properties of the material. This makes the cuticle a versatile material ideally suited to form a variety of skeletal elements that are adapted to different functions and the eco-physiological strains of individual species. This review presents our recent analytical, experimental and theoretical studies on the cuticle, summarising at which hierarchical levels structure and composition are modified to achieve the required physical properties. We describe our multi-scale hierarchical modeling approach based on the results from these studies, aiming at systematically predicting the structure-composition-property relations of cuticle composites from the molecular level to the macro-scale. This modeling approach provides a tool to facilitate the development of optimized biomimetic materials within a knowledge-based design approach.
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Coquilles d'animaux/composition chimique , Coquilles d'animaux/ultrastructure , Isopoda/anatomie et histologie , Adaptation physiologique , Coquilles d'animaux/anatomie et histologie , Coquilles d'animaux/physiologie , Animaux , Évolution biologique , Biomimétique , Carbonate de calcium , Chitine , Isopoda/physiologie , Minéraux , Modèles anatomiquesRÉSUMÉ
BACKGROUND: Our study was aimed to validate a modified RBD (REM sleep behavior disorder) single question (RBD1Q-C), study the prevalence of probable RBD (pRBD) in a rural community based on RBD1Q-C and investigate the association between pRBD and Parkinson's disease (PD). METHODS: The validation study of RBD1Q-C included 32 Chinese participants (14 idiopathic RBD patients and 18 controls). All participants underwent a polysomnogram (PSG). We then conducted a door-to-door survey to estimate the prevalence of pRBD assessed by RBD1Q-C, and its association with PD among 19614 residents who lived in Malu community of Shanghai, China. RESULTS: RBD1Q-C demonstrated a high sensitivity of 100%, a moderate specificity of 55.6%. The agreement between RBD1Q-C and PSG-based RBD diagnosis was good (k = 0.552). PPV of the RBD1Q-C was 63.6% and NPV was 100%. The prevalence of pRBD in Malu community was 4.9%. In people over 50 years old, presence of pRBD was significantly associated with increased risk of having PD (odds ratio = 2.61, 95% CI: 1.56-4.39). CONCLUSION: RBD1Q-C was shown to be a useful screening tool. Based on the RBD1Q-C, we found that pRBD was not rare in Chinese rural population and associated with odds of PD, calling for more attention from patients, caregivers and physicians.
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Dépistage de masse/statistiques et données numériques , Maladie de Parkinson/épidémiologie , Trouble du comportement en sommeil paradoxal/épidémiologie , Santé en zone rurale/statistiques et données numériques , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Chine/épidémiologie , Femelle , Humains , Mâle , Adulte d'âge moyen , Polysomnographie/méthodes , Surveillance de la population , Valeur prédictive des tests , Prévalence , Sensibilité et spécificité , Jeune adulteRÉSUMÉ
BACKGROUND: Both tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined. RESULTS: Here we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion. CONCLUSIONS: Our results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.
Sujet(s)
Marqueurs biologiques tumoraux/métabolisme , Carcinome épidermoïde/anatomopathologie , Transition épithélio-mésenchymateuse , Macrophages/anatomopathologie , Tumeurs de la bouche/anatomopathologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antigènes CD/génétique , Antigènes CD/métabolisme , Antigènes de différenciation des myélomonocytes/génétique , Antigènes de différenciation des myélomonocytes/métabolisme , Marqueurs biologiques tumoraux/génétique , Cadhérines/génétique , Cadhérines/métabolisme , Carcinome épidermoïde/génétique , Carcinome épidermoïde/métabolisme , Lignée cellulaire tumorale , Mouvement cellulaire , Milieux de culture conditionnés/pharmacologie , Femelle , Régulation de l'expression des gènes tumoraux , Humains , Macrophages/métabolisme , Mâle , Adulte d'âge moyen , Tumeurs de la bouche/génétique , Tumeurs de la bouche/métabolisme , Pronostic , Récepteurs de surface cellulaire/génétique , Récepteurs de surface cellulaire/métabolisme , Analyse de survie , Cellules cancéreuses en culture , Vimentine/génétique , Vimentine/métabolismeRÉSUMÉ
To explore the method of explants directly induced bud and establish the tissue culture system of mutiple shoot by means of direct organogenesis, core bud and daughter bulbs (the top of bud stem expanded to form daughter bulb) of T. edulis were used as explants and treated with thidiazuron (TDZ) and 1-naphthlcetic acid (NAA). The results showed that the optimal medium for bud inducted form core bud and daughter bulb were MS + TDZ 2.0 mg x L(-1) + NAA 4.0 mg x L(-1) and MS +TDZ 2.0 mg x L(-1) + NAA 2.0 mg x L(-1) respectively, both of them had a bud induction rate of 72.92%, 79.22%. The optimal medium for cluster buds multiplication was MS + TDZ 0.2 mg x L(-1) + NAA 0.2 mg x L(-1), and proliferation coefficient was 2.23. After proliferation, cluster buds rooting occurred on MS medium with IBA 1.0 mg x L(-1) and the rooting rate was 52.6%, three to five seedlings in each plant. Using core bud and daughter bulb of T. edulis, the optimum medium for adventitious bud directly inducted from daughter bulb, core bud and cluster bud multiplication were screened out and the tissue culture system of multiple shoot by means of direct organogenesis was established.