Genistein is an isoflavone extracted from soybean (Glycine max). This compound has anti-inflammatory, anti-oxidative, and anti-cancer effects; however, the mechanism underlying the effects of ...genistein on IL-1β-stimulated human osteoarthritis (OA) chondrocytes remains unknown. Our objectives in this study were to explore the anti-inflammatory effects of genistein on IL-1β-stimulated human OA chondrocytes and to investigate the potential mechanisms which underlie them. Our results from an in-vitro model of osteoarthritis indicate that genistein inhibits the IL-1β-induced expression of the catabolic factors nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX-2), and matrix metalloproteinases (MMPs). Genistein was shown to stimulate Ho-1 expression, which has been associated with Nrf-2 pathway activation in human chondrocytes. In a rat model, genistein was also shown to attenuate the progression of traumatic osteoarthritis. Taken together, these results demonstrate the effectiveness of genistein in mediating the inflammation associated with joint disorders. Our results also indicate that genistein could potentially serve as an alternative therapeutic treatment for OA.
Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection. Over the past 60 years, DENV has spread throughout tropical regions and currently affects more than 50% of the ...world's population; however, there are as of yet no effective anti‐DENV drugs for clinical treatment. A number of research teams have investigated derivatives of glycolipids as possible agents for the inhibition of DENV. Our objective in this research was to study the antiviral effects of trehalose 6‐caprate (TMC), trehalose 6‐monolaurate (TML), and trehalose 6‐monooleate (TMO), based on reports that the corresponding glycosyl, trehalose, reduces the transmission of Zika virus (ZIKV). We also sought to elucidate the molecular mechanisms underlying inhibition using the RNA isolation and reverse transcription‐quantitative polymerase chain reaction, western blot analysis, median tissue culture infectious dose (TCID50) assay, and immunofluorescence assay and immunochemistry staining, in vitro. This is the first study to demonstrate the TML‐induced inhibition of DENV serotype 2 (DENV‐2) in a dose‐dependent manner. The inhibitory effects of TML in the pretreated, cotreated, and full‐treated groups were confirmed using time of addition assays. We determined that TML restricted viral binding, entry, replication, and release. We also confirmed the efficacy of TML against three clinical isolates of DENV serotypes 1, 3, and 4 (DENV‐1, DENV‐3, and DENV‐4). The findings obtained in this study identify TML as a promising candidate for the development of drugs to treat DENV infection.
Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy ...due to their broad-spectrum of antimicrobial activity and low incidence of bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.
Single-crystal n-type GaN nanowires have been grown epitaxially on a Mg-doped p-type GaN substrate. Piezoelectric nanognerators based on GaN nanowires are investigated by conductive AFM, and the ...results showed an output power density of nearly 12.5 mW/m2. Luminous LED modules based on n-GaN nanowires/p-GaN substrate have been fabricated. CCD images of the lighted LED and the corresponding electroluminescence spectra are recorded at a forward bias. Moreover, the GaN nanowire LED can be lighted up by the power provided by a ZnO nanowire based nanogenerator, demonstrating a self-powered LED using wurtzite-structured nanomaterials.
Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. ...This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28‐joint Disease Activity Score with erythrocyte sedimentation rate (DAS28‐ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28‐ESR. Overall, 16 cell subsets presented significant differences between the non‐response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28‐ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi.
Bacterial extracellular DNA (eDNA) and activated platelets have been found to contribute to biofilm formation by Streptococcus mutans on injured heart valves to induce infective endocarditis (IE), ...yet the bacterial component directly responsible for biofilm formation or platelet adhesion remains unclear. Using in vivo survival assays coupled with microarray analysis, the present study identified a LiaR-regulated PspC domain-containing protein (PCP) in S. mutans that mediates bacterial biofilm formation in vivo. Reverse transcriptase- and chromatin immunoprecipitation-polymerase chain reaction assays confirmed the regulation of pcp by LiaR, while PCP is well-preserved among streptococcal pathogens. Deficiency of pcp reduced in vitro and in vivo biofilm formation and released the eDNA inside bacteria floe along with reduced bacterial platelet adhesion capacity in a fibrinogen-dependent manner. Therefore, LiaR-regulated PCP alone could determine release of bacterial eDNA and binding to platelets, thus contributing to biofilm formation in S. mutans-induced IE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Emergency surgery for acute type A aortic dissection (AAAD) was usually avoided or denied in octogenarians because of high surgical mortality. Refined surgical techniques and improved ...postoperative care have led to an improved in‐hospital outcome. However, a significant number of operative survivors suffered from postoperative complications and had compromised quality of life. We sought to assess the clinical outcome of emergency surgery using a standard conservative approach in octogenarians with AAAD.
Methods
From 2004 to 2021, 123 patients underwent emergency surgery for AAAD by one surgeon using a standard conservative approach with right subclavian artery cannulation, no aortic cross‐clamp, selective antegrade cerebral perfusion, moderate systemic hypothermia, reinforced sandwich technique, and a strategy of limited aortic resection. Hospital and late outcomes were assessed in patients with age >80 years.
Results
Eighteen patients (15%) were octogenarians with seven males (39%) and median age of 82 years (range, 80–89). Hypertension was present in six patients (33%). None had diabetes mellitus, Marfan, or bicuspid aortic valve. Dissection was intramural hematoma in six (33%) and DeBakey type I in 15 patients (83%). Cardiac tamponade with shock was present in seven patients (39%). Ascending aortic grafting was performed in 17 patients, and additional hemiarch replacement in one patient. The hospital mortality rate was 17% (3/18). Fourteen patients (82%) were alive and well at discharge.
Conclusions
Emergency surgery for AAAD using a standard conservative approach showed an improved outcome in octogenarians. The majority of patients could return home with an acceptable living.
The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI.
We analysed serum DKK1 levels and ...their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S).
Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001).
Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.
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