Demands for ultrahigh strength in structural materials have been steadily increasing in response to environmental issues. Maraging alloys offer a high tensile strength and fracture toughness through ...a reduction of lattice defects and formation of intermetallic precipitates. The semi-coherent precipitates are crucial for exhibiting ultrahigh strength; however, they still result in limited work hardening and uniform ductility. Here, we demonstrate a strategy involving deformable semi-coherent precipitates and their dynamic phase transformation based on a narrow stability gap between two kinds of ordered phases. In a model medium-entropy alloy, the matrix precipitate acts as a dislocation barrier and also dislocation glide media; the grain-boundary precipitate further contributes to a significant work-hardening via dynamic precipitate transformation into the type of matrix precipitate. This combination results in a twofold enhancement of strength and uniform ductility, thus suggesting a promising alloy design concept for enhanced mechanical properties in developing various ultrastrong metallic materials.
Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to ...achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.
Background and Aim
The efficacy of treatment with multispecies probiotics on irritable bowel syndrome (IBS) symptoms and the alterations of gut microbiota in patients who have taken probiotics were ...investigated.
Methods
This randomized, double‐blind, placebo‐controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks. The primary efficacy end‐point was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary end‐points were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the 4 weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real‐time polymerase chain reaction assays.
Results
The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) versus 37.5% (9/24) (P < 0.05). Secondary end‐points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus, and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group.
Conclusions
Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • STAT3 signaling pathway plays a critical role in tumorigenesis. • BGM inhibited the constitutive activation of STAT3 signaling cascade. • BGM induced the expression of the tyrosine ...phosphatase SHP-1. • BGM is a novel blocker of STAT3 activation pathway thus may have a potential in therapy of MM and other cancers.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Display omitted
•Individual and mixture of antibiotics at 0.1mg/L did not impair growth of embryos.•Zebrafish larvae preferred blue over yellow regardless of antibiotic’s presence.•Swimming behavior ...of 5-dpf larvae significantly changed relative to exposure time.•Metabolites choline, guanosine, and ADP were regulated in the exposed zebrafish.•Antibiotics’ mechanism of action seems to play a role in zebrafish’s metabolism.
Antibiotics in the aquatic environment are dispersed through anthropogenic activities at low concentrations. Despite their sub lethal concentration, these biologically active compounds may still have adverse effects to non-target species. This study examined the response of adult zebrafish to 0.1mg/L concentration of clarithromycin, florfenicol, sulfamethazine, and their mixture using environmental metabolomics. Embryo and larvae of the fish were also used to assess fish embryo acute toxicity and behavior tests respectively. The fish embryo toxicity test did not show any inhibition of growth and development of the embryos after 96h of exposure to the antibiotics. Changes in swimming activity were seen in 5-dpf larvae which is believed to be correlated with the length of exposure to the compounds. Meanwhile, environmental metabolomics revealed diverse metabolites and pathways that were affected after 72h of exposure of the adult fish to sub-lethal concentration of the compounds. We found that even at low concentration of the antibiotics, behavioral and metabolic effects were still observed despite the lack of visible morphological changes. Further studies involving other aquatic organisms and bioactive compounds are encouraged to strengthen the findings presented in this novel research.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background. Chinese herbal medicines (CHMs) have been widely used in the treatment of cervicogenic dizziness (CGD) based on their empirical effectiveness and safety. Herein, we reviewed and evaluated ...the clinical evidence of the efficacy and safety of CHMs for CGD. Methods. Among the relevant studies published in 11 electronic databases up to December 2021, only randomised controlled trials were included. Methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomised trials, and the strength of evidence for the main outcomes was evaluated using the grading of recommendations assessment, development, and evaluation system. Results. All 35 included randomised controlled trials with 3,862 participants were conducted with six types of modified CHM and four types of active controls. More than half of the included studies were of low quality because of the high risk of bias due to deviations from intended interventions. CHM plus active control was more effective in the treatment of CGD than active control alone. CHM plus anti-vertigo drugs, CHM plus manual therapy, CHM plus acupuncture therapy, and CHM plus manual and acupuncture therapy were all effective in treating CGD, with CHM plus manual and acupuncture therapy showing the most reliable effect. All CHMs were effective for specific patterns of CGD when administered with active controls, with Dingxuan Tang and Yiqi Congming Tang demonstrating the most reliable effects. No serious adverse events were reported in any of the included studies. Conclusion. The current evidence suggests that CHM may enhance the treatment of CGD when combined with other treatments without serious adverse events. Further high-quality evidence is needed to draw definitive conclusions.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Mitochondrial dysfunction is a key element in the progression of Parkinson's disease (PD). The inefficient operation of the electron transport chain (ETC) impairs energy production and enhances the ...generation of oxidative stress contributing to the loss of dopaminergic cells in the brain. ATPase inhibitory factor 1 (IF1) is a regulator of mitochondrial energy metabolism. IF1 binds directly to the F
Fo ATP synthase and prevents ATP wasting during compromised energy metabolism. In this study, we found treatment with IF1 protects mitochondria against PD-like insult in vitro. SH-SY5Y cells treated with IF1 were resistant to loss of ATP and mitochondrial inner membrane potential during challenge with rotenone, an inhibitor of complex I in the ETC. We further demonstrated that treatment with IF1 reversed rotenone-induced superoxide production in mitochondria and peroxide accumulation in whole cells. Ultimately, IF1 decreased protein levels of pro-apoptotic Bax, cleaved caspase-3, and cleaved PARP, rescuing SH-SY5Y cells from rotenone-mediated apoptotic death. Administration of IF1 significantly improved the results of pole and hanging tests performed by PD mice expressing human α-synuclein. This indicates that IF1 mitigates PD-associated motor deficit. Together, these findings suggest that IF1 exhibits a neuroprotective effect preventing mitochondrial dysfunction in PD pathology.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Lumbar herniated intervertebral disc (LHIVD) is a common disease that causes low back pain. Traditional Chinese medicine (TCM) with conservative conventional treatment is known to be effective at ...treating LHIVD, but evidence for complex TCM therapies with conventional intervention has not been sufficiently collected to facilitate quality assessment and synthesis of data.
Studies were retrieved from the following databases: the Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE/PubMed, 7 Korean databases (Korean Studies Information Service System, Korean Traditional Knowledge Portal, Oriental Medicine Advanced Searching Integrated System, Korean National Assembly Digital Library, Korean Association of Medical Journal Editors, National Digital Science Library, and Database Periodical Information Academic), Japan Medical Abstracts Society, and Chinese National Knowledge Infrastructure. The risk of bias of the included studies will be assessed using the Cochrane Assessment Tool for Risk of Bias. Eligible studies were quantitatively synthesized through a meta-analysis. The primary outcome will be pain scales, and the secondary outcomes will include range of motion, questionnaires for lumbar function, questionnaire for quality of life, etc.
Ethical approval was waived for this study protocol because it does not provide any patient data. The results of this review will be disseminated through peer-reviewed publications.
DOI 10.17605/OSF.IO/K7NJ8 (https://osf.io/k7nj8).
Abstract Signal transducers and activators of transcription (STAT)-3 is a latent cytosolic transcription factor that has been closely associated with survival, proliferation, chemoresistance, and ...metastasis of tumor cells. Whether the anti-proliferative, pro-apoptotic, and anti-metastatic effects of capillarisin (CPS), derived from Artemisia capillaris (Compositae), are linked to its capability to inhibit STAT3 activation was investigated. We found that CPS specifically inhibited both constitutive and inducible STAT3 activation at tyrosine residue 705 but not at serine residue 727 in human multiple myeloma cells. Besides the inhibition of STAT3 phosphorylation, CPS also abrogated STAT3 constitutive activity and nuclear translocation. The suppression of STAT3 was mediated through the inhibition of activation of upstream JAK1, JAK2, and c-Src kinases. Treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate treatment reversed the CPS-induced down-regulation of JAK1/2 and STAT3, thereby suggesting the involvement of a PTP. Indeed, knockdown of the SHP-1 and SHP-2 genes by small interfering RNA suppressed the ability of CPS to inhibit JAK1 and STAT3 activation, suggesting the critical role of both SHP-1 and SHP-2 in its possible mechanism of action. CPS downregulated the expression of STAT3-regulated antiapoptotic and proliferative gene products; and this correlated with suppression of cell viability, the accumulation of cells in sub-G1 phase of cell cycle and induction of apoptosis. Moreover, CPS potentiated bortezomib-induced apoptotic effects in MM cells, and this correlated with down-regulation of various gene products that mediate cell proliferation (Cyclin D1 and COX-2), cell survival (Bcl-2, Bcl-xl, IAP1, IAP2, and Survivin), invasion (MMP-9), and angiogenesis (VEGF). Thus, overall, our results suggest that CPS is a novel blocker of STAT3 activation and thus may have a potential in negative regulation of growth, metastasis, and chemoresistance of tumor cells.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK