Boltongoode9381
Evaluation of the in-vivo anti-inflammatory activity of the methanolic extract obtained from the aerial parts of Mitracarpus frigidus (MFM) in the infection caused by two Salmonella strains and its chemical fingerprint by UFLC-quadrupole time of flight-MS.
The efficacy of MFM was investigated in a classical in-vivo Salmonella infection mouse model. A Salmonella reference strain (ATCC 13311) and a clinical isolate were used to infect mice and then MFM was orally administered during 14 days. At the end of the treatment with MFM, the infection and inflammatory levels were assayed.
MFM treatment showed a significant reduction in mice mortality by Salmonella infection and, also, did not cause alterations in the liver function. Inhibitions of inflammatory and oxidative stress mediators [malondialdehyde (MDA), catalase, and metalloproteinase] were possibly involved in the observed effects. Chlorogenic acid, clarinoside, quercetin-pentosylhexoside, rutin, kaempferol-3O-rutinoside, kaempferol-rhamnosylhexoside and 2-azaanthraquinone were identified in MFM.
MFM was effective in some inflammatory parameters, in the experimental conditions that were used in the study. The results presented in this study and the previous in-vitro anti-Salmonella activity reported by our research group reinforce the importance of MFM studies to considerer it as an alternative treatment for salmonellosis.
MFM was effective in some inflammatory parameters, in the experimental conditions that were used in the study. The results presented in this study and the previous in-vitro anti-Salmonella activity reported by our research group reinforce the importance of MFM studies to considerer it as an alternative treatment for salmonellosis.
Calocybe indica is a famous nutritious food in Asian countries and one of the most widely cultivated mushrooms in the world. Here, we have isolated crude polysaccharides from this mushroom, characterized it and investigated its antioxidant and immunostimulatory potential.
The polysaccharide was chemically characterized by spectrophotometry, FTIR and high-performance thin layer chromatography and tested its antioxidant potential by in vitro assays. Immunomodulatory activity and its underlying signalling process were ascertained in RAW 264.7 cells.
The polysaccharide consisted of D-glucose (β-linked sugars), D-mannose and D-galactose, where backbone was organized in random coil structure. Preliminary investigation of the bioactivity of the polysaccharide revealed its antioxidant potential. The polysaccharide could noticeably induce phagocytic activity and production of immune mediators in macrophage cells. The polysaccharide was found to enhance the expression of pro-inflammatory cytokines and activate NF-κB signalling pathway by overexpressing MyD88, Iκ-Bα and NF-κB. Further studies indicated the polysaccharide binds to the toll-like receptor 4 to manifest its immunostimulatory activity in macrophage cells.
Our findings indicate potential therapeutic properties of the crude polysaccharide of C. indica which might provide the means to treat various radical induced and immunodeficiency disorders in the days to come.
Our findings indicate potential therapeutic properties of the crude polysaccharide of C. indica which might provide the means to treat various radical induced and immunodeficiency disorders in the days to come.
To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.
TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.
The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.
PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.P2RX2 encodes the P2X2 receptor, which is an adenosine triphosphate (ATP) gated (purinoreceptor) ion channel. P2RX2 c. 178G > T (p.V60L) mutation was previously identified in two unrelated Chinese families, as the cause of human DFNA41, a form of dominant, early-onset and progressive sensorineural hearing loss. We generated and characterized a knock-in mouse model based on human p.V60L mutation that recapitulates the human phenotype. Heterozygous KI mice started to exhibit hearing loss at 21-day-old and progressed to deafness by 6-month-old. Vestibular dysfunction was also observed in mutant mice. Abnormal morphology of the inner hair cells and ribbon synapses was progressively observed in KI animals suggesting that P2rx2 plays a role in the membrane spatial location of the ribbon synapses. These results suggest that P2rx2 is essential for acoustic information transfer, which can be the molecular mechanism related to hearing loss.In the current study, we investigated the protective role of citalopram against cognitive decline, impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective autophagy, mitophagy and synaptic dysfunction in APP transgenic mouse model of Alzheimer's disease (ad). We treated 12-month-old wild-type (WT) and age-matched transgenic APP mice with citalopram for 2 months. Using Morris Water Maze and rotarod tests, quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed cognitive behavior, RNA and protein levels of mitochondrial dynamics, biogenesis, autophagy, mitophagy, synaptic, ad-related and neurogenesis genes in wild-type and APP mice treated and untreated with citalopram. Citalopram-treated APP mice relative to citalopram-untreated APP mice exhibited improved cognitive behavior. Increased levels of mRNA associated with mitochondrial fission and ad-related genes; decreased levels of fusion, biogenesis, autophagy, mitophagy, synaptic and Aβ-induced injuries in patients with depression, anxiety and ad.
Animal studies suggested that vitamin D might decrease insulin resistance. Estrogen increased insulin sensitivity and glucose tolerance in rodents. However, sex-specific association of vitamin D with insulin resistance in humans remains unclear.
To investigate the sex-dependency of the association of insulin resistance and 25(OH)D in a large Caucasian population.
Cross-sectional study from out-patients' blood samples with measurements of 25(OH)D and HOMA-IR drawn at exactly the same day (N=1887). This cohort was divided into three groups i) group with vitamin D deficiency (n=1190), ii) group with vitamin D sufficiency (N=686)), iii) vitamin D excess groups (n=11), the vitamin D excess group was excluded from further analysis due to the small size.
Analysis of the entire study population showed that serum 25-hydroxyvitamin D was inversely associated with HOMA-IR (rs=-0.19, P<0.0001). When considering the vitamin D status, this association was only seen in the vitamin D deficiency group, but not in ts to be proven in adequately designed double-blind placebo-controlled clinical studies.Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age-related FA differences were widespread but were strongly associated with differences in multi-fiber complexity (CX), suggesting that they reflected differences in crossing fibers in addition to structural differences in individual fiber segments. FBA also revealed a frontolimbic locus of age-related effects and provided insights into distinct microstructural changes underlying them. Specifically, age differences in fiber density were prominent in fornix, bilateral anterior internal capsule, forceps minor, body of the corpus callosum, and corticospinal tract, while age differences in fiber cross section were largest in cingulum bundle and forceps minor. These results provide novel insights into specific structural differences underlying major WM differences associated with aging.It is widely acknowledged that having experience conducting research is invaluable for undergraduate science students. Most undergraduate research is undertaken by students in a mentor's laboratory, but this limits the number of opportunities for students, as each laboratory can only take on a certain number of undergraduate researchers each semester. Additionally, it is also widely acknowledged that it is difficult for teachers to meet research goals while providing the best possible coursework for undergraduate students. find more Both of these bottlenecks can be circumvented via Classroom Undergraduate Research Experiences (CUREs), which integrate research into the curricula of structured undergraduate classes. Students enrolled in classes that include CUREs conduct research to address open-ended questions as part of their coursework. In this commentary, I describe the many ways in which CUREs are helpful for students and teachers, as well as considerations for designing successful CUREs. I provide several examples of CUREs from Microbial Physiology laboratory classes and Genomics classes that I have taught. Results from these CUREs have been successfully integrated into many peer-reviewed publications in which the students are co-authors, which has been a boon both to students' post-baccalaureate opportunities, as well as my research agenda.Previous studies have shown the porphobilinogen synthase (PBGS) zinc-binding mechanism and its conservation among the living cells. However, the precise molecular interaction of zinc with the active center of the enzyme is unknown. In particular, quantum chemistry techniques within the density functional theory (DFT) framework have been the key methodology to describe metalloproteins, when one is looking for a compromise between accuracy and computational feasibility. Considering this, we used DFT-based models within the molecular fractionation with conjugate caps scheme to evaluate the binding energy features of zinc interacting with the human PBGS. Besides, phylogenetic and clustering analyses were successfully employed in extracting useful information from protein sequences to identify groups of conserved residues that build the ions-binding site. Our results also report a conservative assessment of the relevant amino acids, as well as the benchmark analysis of the calculation models used. The most relevant intermolecular interactions in Zn2+-PBGS are due to the amino acids CYS0122, CYS0124, CYS0132, ASP0169, SER0168, ARG0221, HIS0131, ASP0120, GLY0133, VAL0121, ARG0209, and ARG0174.
