Dietary fiber functions as a prebiotic to determine the gut microbe composition. The gut microbiota influences the metabolic functions and immune responses in human health. The gut microbiota and ...metabolites produced by various dietary components not only modulate immunity but also impact various organs. Although recent findings have suggested that microbial dysbiosis is associated with several respiratory diseases, including asthma, cystic fibrosis, and allergy, the role of microbiota and metabolites produced by dietary nutrients with respect to pulmonary disease remains unclear. Therefore, we explored whether the gut microbiota and metabolites produced by dietary fiber components could influence a cigarette smoking (CS)-exposed emphysema model. In this study, it was demonstrated that a high-fiber diet including non-fermentable cellulose and fermentable pectin attenuated the pathological changes associated with emphysema progression and the inflammatory response in CS-exposed emphysema mice. Moreover, we observed that different types of dietary fiber could modulate the diversity of gut microbiota and differentially impacted anabolism including the generation of short-chain fatty acids, bile acids, and sphingolipids. Overall, the results of this study indicate that high-fiber diets play a beneficial role in the gut microbiota-metabolite modulation and substantially affect CS-exposed emphysema mice. Furthermore, this study suggests the therapeutic potential of gut microbiota and metabolites from a high-fiber diet in emphysema via local and systemic inflammation inhibition, which may be useful in the development of a new COPD treatment plan.
Background
In experimental models, bone marrow‐derived mesenchymal stem cells (BM‐MSCs) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects. However, there have been ...no studies in humans with alcoholic cirrhosis.
Aim
The aim of this study was to elucidate the antifibrotic effect of BM‐MSCs in patients with alcoholic cirrhosis, as a phase II clinical trial.
Methods
Twelve patients (11 males, 1 female) with baseline biopsy‐proven alcoholic cirrhosis who had been alcohol free for at least 6 months were enrolled. BM‐MSCs were isolated from each patient's BM and amplified for 1 month, and 5 × 107 cells were then injected twice, at weeks 4 and 8, through the hepatic artery. One patient was withdrawn because of ingestion of alcohol. Finally, 11 patients completed the follow‐up biopsy and laboratory tests at 12 weeks after the second injection. The primary outcome was improvement in the patients’ histological features.
Results
According to the Laennec fibrosis system, histological improvement was observed in 6 of 11 patients (54.5%). The Child‐Pugh score improved in ten patients (90.9%) and the levels of transforming growth factor‐β1, type 1 collagen and α‐smooth muscle actin significantly decreased (as assessed by real‐time reverse transcriptase polymerase chain reaction) after BM‐MSCs therapy (P < 0.05). No significant complications or side effects were observed during this study.
Conclusions
Bone marrow‐derived mesenchymal stem cells therapy in alcoholic cirrhosis induces a histological and quantitative improvement of hepatic fibrosis.
Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently ...emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DR
CD11b
CD33
CD14
human MDSCs and CD11b
Ly6G
Ly6C
mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis. CD11b
Ly6C
monocytes isolated from autoimmune uveoretinitis mice were able to suppress T cell proliferation in culture, and adoptive transfer of the cells accelerated the remission of autoimmune uveoretinitis in mice. Alternatively, depletion of CD11b
Ly6C
monocytes at the resolution phase, but not CD11b
Ly6G
granulocytes, exacerbated the disease. These findings collectively indicate that monocytic MDSCs serve as regulatory cells mediating the resolution of autoimmune uveoretinitis.
Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To ...modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.
A new kind of flexible strain sensor based on a reduced graphene oxide field‐effect transistor (rGO FET) with ultrasensitivity, stability, and repeatability for the detection of tensile and ...compressive strains is demonstrated. The novelty of the rGO FET strain sensor is the incorporation of a rGO channel as a sensing layer in which the electrical resistance can be greatly modified upon application of an extremely low level of strain resulting in an intrinsically amplified sensing signal. The rGO FET device is ultrasensitive to extremely low strain levels, as low as 0.02%. Due to weak coupling between adjacent nanosheets, therefore, upon applying small levels of strain into the rGO thin film, a modulation of the internanosheet resistance (Rinter) is expected, inducing a large change in the transconductance of the rGO FET. Using a simple printing and self‐assembly process, the facile fabrication of an rGO FET array over a large area is also demonstrated. In addition, the device can detect small and rapid physical movements of the human body.
The novelty of the rGO FET strain sensor is the incorporation of an rGO channel as a sensing layer in which modulation of the inter‐nanosheet resistance (Rinter) due to weak coupling between adjacent nanosheets induces a large change in the transconductance of the rGO FET. The rGO FET device is ultrasensitive to extremely low strain levels, as low as 0.02%.
Herein, we describe the synthesis of highly water-dispersible and biocompatible 3D adsorbents via a rapid two-step strategy employing a mesoporous magnetic nanomulberry-shaped Fe
O
(MNM) on ...diatomaceous earth (DE) and cucurbituril (CB; MNM-DE-CB). Coating of CB on the surface of MNM-DE via hydrogen bonds not only enhanced the dispersibility of CB, but also improved the stability of MNM-DE. The ability of the adsorbent to remove dyes from water was investigated as a function of metal ions, solution pH, temperature, and concentration to determine optimum reaction conditions. Unlike MNM-DE, MNM-DE-CB exhibited highly efficient, rapid dye removal and recyclability in aqueous solution, and low cytotoxicity toward cancer cells in drug delivery tests. MNM-DE-CB is a promising green adsorbent with potential for diverse applications including water remediation, interface catalysis, bio-sample preparation, and drug delivery.
Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we ...investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model.
The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays.
According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation.
BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Infectious diseases, especially pathogenic infections, are a growing threat to public health worldwide. Since pathogenic bacteria usually exist in complex matrices at very low concentrations, the ...development of technology for rapid, convenient, and biocompatible sample enrichment is essential for sensitive diagnostics. In this study, a cucurbit6uril (CB) supermolecular decorated amine-functionalized diatom (DA) composite was fabricated to support efficient sample enrichment and in situ nucleic acid preparation from enriched pathogens and cells. CB was introduced to enhance the rate and effectiveness of pathogen absorption using the CB-DA composite. This novel CB-DA composite achieved a capture efficiency of approximately 90% at an
concentration of 10⁶ CFU/mL within 3 min. Real-time PCR analyses of DNA samples recovered using the CB-DA enrichment system showed a four-fold increase in the early amplification signal strength, and this effective method for capturing nucleic acid might be useful for preparing samples for diagnostic systems.
Brain-derived exosomes released into the blood are considered a liquid biopsy to investigate the pathophysiological state, reflecting the aberrant heterogeneous pathways of pathological progression ...of the brain in neurological diseases. Brain-derived blood exosomes provide promising prospects for the diagnosis of neurological diseases, with exciting possibilities for the early and sensitive diagnosis of such diseases. However, the capability of traditional exosome isolation assays to specifically isolate blood exosomes and to characterize the brain-derived blood exosomal proteins by high-throughput proteomics for clinical specimens from patients with neurological diseases cannot be assured. We report a magnetic transferrin nanoparticles (MTNs) assay, which combined transferrin and magnetic nanoparticles to isolate brain-derived blood exosomes from clinical samples.
The principle of the MTNs assay is a ligand-receptor interaction through transferrin on MTNs and transferrin receptor on exosomes, and electrostatic interaction via positively charged MTNs and negatively charged exosomes to isolate brain-derived blood exosomes. In addition, the MTNs assay is simple and rapid (< 35 min) and does not require any large instrument. We confirmed that the MTNs assay accurately and efficiently isolated exosomes from serum samples of humans with neurodegenerative diseases, such as dementia, Parkinson's disease (PD), and multiple sclerosis (MS). Moreover, we isolated exosomes from serum samples of 30 patients with three distinct neurodegenerative diseases and performed unbiased proteomic analysis to explore the pilot value of brain-derived blood protein profiles as biomarkers.
Using comparative statistical analysis, we found 21 candidate protein biomarkers that were significantly different among three groups of neurodegenerative diseases.
The MTNs assay is a convenient approach for the specific and affordable isolation of extracellular vesicles from body fluids for minimally-invasive diagnosis of neurological diseases.
The isolation of bio-molecules such as proteins and nucleic acids is a necessary step for both diagnostic and analytical processes in the broad fields of research and clinical applications. Although ...a myriad of isolation technologies have been developed, a method for simultaneous protein and nucleic acid isolation has not been explored for clinical use. Obtaining samples from certain cancers or rare diseases can be difficult. In addition, the heterogeneity of cancer tissues typically leads to inconsistent results when analyzing biomolecules. We here describe a homobifunctional imidoester (HI)-based microfluidic system for simultaneous DNA and protein isolation from either a solid or liquid single biopsy sample. An efficient and cost effective microfluidic design with less air bubbles was identified among several candidates using simulation and experimental results from the streamlining of isolation processing. HI groups were used as capture reagents for the simultaneous isolation of bio-molecules from a single specimen in a single microfluidic system. The clinical utility of this system for the simultaneous isolation of DNA and proteins within 40 min was validated in cancer cell lines and 23 tissue biopsies from colorectal cancer patients. The quantity of isolated protein and DNA was high using this system compared to the spin-column method. This HI-based microfluidic system shows good rapidity, affordability, and portability in the isolation of bio-molecules from limited samples for subsequent clinical analysis.
The isolation of bio-molecules such as proteins and nucleic acids is a necessary step for both diagnostic and analytical processes in the broad fields of research and clinical applications.
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