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.
This study aimed to investigate the risk factors for mechanical failure of cement spacers and the impact on hip function after two-stage exchange arthroplasty for periprosthetic joint infection ...(PJI).
Thirty-one patients (19 males and 12 females) with hip PJIs underwent resection arthroplasty and implantation of cement spacers from January 2014 to December 2015. Patients who encountered spacer-associated mechanical complications in the interim period (14 of 31) were compared with those without complications (17 of 31). Complications were defined as spacer dislocation, spacer fracture, spacer fracture with dislocation, and femoral fracture during or following spacer implantation. Hip functional outcome was assessed using the Harris hip score (HHS). Treatment success was defined according to the following criteria: (1) no symptoms or signs indicative of infection; (2) no PJI-related mortality; and (3) no subsequent surgical intervention for infection after reimplantation surgery. Multivariate logistic regression and Kaplan-Meier survival curves were used for analysis.
Fourteen patients (14/31 = 45%) suffered at least one spacer-related complication within the interim period. The development of spacer complications was associated with a younger age (odds ratio OR 0.91, 95% confidence interval CI 0.83-1.00, p = 0.045) and chronic PJI (OR 14.7, 95% CI 1.19-182, p = 0.036). Patients with spacer complications also had a lower median HHS (37 vs. 60, p < 0.001) before reimplantation in comparison to those without spacer complications. After reimplantation, the two groups had a similar median HHS (90 vs. 89, p = 0.945). Two patients did not undergo reimplantation due to extensive comorbidities, and subsequently retained the antibiotic spacer for definitive treatment. The 2-year treatment success rate was 84.6% in the spacer-complication group and 87.5% in the non-spacer-complication group (p = 0.81).
There was a high complication rate for articulating PMMA spacers during the interim period of two-stage revision total hip arthroplasty. A young age and chronic infection were the primary risk factors associated with mechanical complications. Patients at high risk of spacer-related mechanical complications should be advised accordingly by surgeons. Knowing the possible risk factors, surgeons should educate patients thoroughly to avoid spacer complications, thereby increasing patient satisfaction in the interim stage.
Prognostic Level III.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In diffuse large B-cell lymphoma (DLBCL), sarcopenia is associated with increased side-effects of chemotherapy and poor survival, especially in elderly patients. Anemia, a complex condition resulting ...from cancer itself and inflammation, might have a correlation with loss of muscle mass and might also indicate a worse outcome. In this study, we aimed to investigate the association of the skeletal muscle index (SMI) at the third lumbar vertebra (L3) with hemoglobin (Hb) levels and its predictive value for the outcome of DLBCL.
The study included patients, aged 70 or older, newly diagnosed with DLBCL who received immunochemotherapy. Sex-specific L3-SMI was measured by computed tomography, and Hb levels before treatment were recorded. The Kaplan-Meier method and Cox regression model were used to analyze survival and prognostic factors.
Anemia was correlated with a low SMI. The presence of either low L3-SMI or anemia (Hb <10.5 g/l) indicated a poor prognosis for both progression-free and overall survival. A novel score combining L3-SMI, and Hb and lactate dehydrogenase levels as independent predictive factors was proposed for treatment response, progression-free and overall survival after adjusting for International Prognostic Index.
This study highlights the importance of sarcopenia and anemia in patients with DLBCL, particularly in the elderly population. The proposed novel score combining L3-SMI, Hb, and lactate dehydrogenase may provide additional prognostic information for patients with DLBCL, aiding in treatment decisions and management.
Salicylic acid (SA), an essential regulator of plant defense, is derived from chorismate via either the phenylalanine ammonia lyase (PAL) or the isochorismate synthase (ICS) catalyzed steps. The ICS ...pathway is thought to be the primary contributor of defense-related SA, at least in Arabidopsis. We investigated the relative contributions of PAL and ICS to defenserelated SA accumulation in soybean (Glycine max).
Soybean plants silenced for five PAL isoforms or two ICS isoforms were analyzed for SA concentrations and SA-derived defense responses to the hemibiotrophic pathogens Pseudomonas syringae and Phytophthora sojae.
We show that, unlike in Arabidopsis, PAL and ICS pathways are equally important for pathogen-induced SA biosynthesis in soybean. Knock-down of either pathway shuts down SA biosynthesis and abrogates pathogen resistance. Moreover, unlike in Arabidopsis, pathogen infection is associated with the suppression of ICS gene expression. Pathogen-induced biosynthesis of SA via the PAL pathway correlates inversely with phenylalanine concentrations. Although infections with either virulent or avirulent strains of the pathogens increase SA concentrations, resistance protein-mediated response to avirulent P. sojae strains may function in an SA-independent manner.
These results show that PAL- and ICS-catalyzed reactions function cooperatively in soybean defense and highlight the importance of PAL in pathogen-induced SA biosynthesis.
Partial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells ...require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging.
Gene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan-Meier curves of estimated overall survival were compared for statistical difference using the log-rank test.
Compared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal
and
as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas,
was a poor marker not only for head and neck cancer but also for additional six cancer types and
was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types.
As the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that
and
, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.
Many countries have allowed farmers to feed β-adrenergic receptor agonists, such as ractopamine (Rac), to animals to improve the quality of their meat. However, Rac consumption can cause health ...problems for humans; thus, detecting Rac in meat before its packaging is essential. Consequently, this study developed a simple and sensitive electrochemical sensor by modifying a glassy carbon electrode (GCE) with Nafion/silver nanoparticles (Nafion/AgNPs). When this electrochemical sensor is used to detect Rac, electrostatic interaction occurs between Nafion and Rac, and the AgNPs oxidize Rac; thus, the accumulation and electrochemical sensing of Rac are achieved. Differential pulse voltammetry indicated that the as-prepared Nafion/AgNP-GCE sensor exhibited suitable electrochemical sensing ability under optimum conditions (6.0 μL of 0.10% Nafion/AgNPs in a Britton-Robertson buffer solution with a pH of 1.8, an accumulation potential of -0.2 V, and a Rac accumulation duration of 300 s). Moreover, this sensor has an extremely low limit of detection and high sensitivity (1.60 × 10
ppm and 2.14 μA/ppm, respectively) in the Rac concentration range 7.50 × 10
-1.00 ppm. The as-prepared sensor also exhibits satisfactory reproducibility and storage stability, with the corresponding relative standard deviations (RSDs) being 4.27% (
= 5) and 1.56% (
= 10), respectively. The proposed electrochemical sensor was successfully used to determine the Rac content in pig liver samples, with spiked recoveries of 95.2-101.8% and RSDs of 0.55-4.83% being achieved.
This study delves into the green synthesis and multifaceted applications of three types of carbon quantum dots (CQDs), namely, CQDs-1, CQDs-2, and CQDs-3. These CQDs were innovatively produced ...through a gentle pyrolysis process from distinct plant-based precursors: genipin with glucose for CQDs-1, genipin with extracted gardenia seeds for CQDs-2, and genipin with whole gardenia seeds for CQDs-3. Advanced analytical techniques, including X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR), were employed to detail the CQDs’ structural and surface characteristics, revealing their unique functional groups and surface chemistries. The study further explores the CQDs’ bioimaging potential, where confocal fluorescence microscopy evidenced their swift uptake by Escherichia coli bacteria, indicating their suitability for bacterial imaging. These CQDs were also applied in the synthesis of gold nanoparticles (AuNPs), acting as reducing agents and stabilizers. Among these, CQD3-AuNPs were distinguished by their remarkable stability and catalytic efficiency, achieving a 99.7% reduction of 4-nitrophenol to 4-aminophenol in just 10 min and maintaining near-complete reduction efficiency (99.6%) after 60 days. This performance notably surpasses that of AuNPs synthesized using sodium citrate, underscoring the exceptional capabilities of CQD3-AuNPs. These insights pave the way for leveraging CQDs and CQD-stabilized AuNPs in bacterial imaging and catalysis, presenting valuable directions for future scientific inquiry and practical applications.
We report a new design of spin-Seebeck diode using two-dimensional spin semiconductors such as sawtooth-like (ST) silicence nanoribbons (SiNRs), to generate unidirectional spin currents with a ...temperature gradient. ST SiNRs have subbands with opposite spins across the Fermi level and hence the flow of thermally excited carriers may produce a net spin current but not charge current. Moreover, we found that even-width ST SiNRs display a remarkable negative differential thermoelectric resistance due to a charge-current compensation mechanism. In contrast, odd-width ST SiNRs manifest features of a thermoelectric diode and can be used to produce both charge and spin currents with temperature gradient. These findings can be extended to other spin semiconductors and open the door for designs of new materials and spin caloritronic devices.
In Taiwan, numbers of patients with the acquired immunodeficiency syndrome (AIDS) have been increasing in recent years. We present esophageal disease of different causes in 5(16%) heterosexual men ...among 31 AIDS patients over a 5-year period. Major symptoms included mild dysphagia in 4 (80%) patients and odynophagia in 3 (60%) patients. The duration of symptoms varied from 3 days to 6 months. The symptoms occurred before the diagnosis of AIDS in 3 patients. At esophagogastroduodenoscopy (endoscopy), all 5 patients had esophagitis and/or esophageal ulcers proved by histopathologic evaluation. Four had Candida esophagitis, 3 had cytomegalovirus esophagitis/ulcers and 2 had idiopathic esophageal ulcerations (IEU). Three patients had different esophagitis/ulcers at the same time or during follow-up. The median CD4 lymphocyte count at the time of diagnosis of esophageal disease was 12.2 cells/mm3 (range, 3 to 35 cells/mm3). The endoscopic pictures of the different causes of esophagitis/ ulcers lack uniformity in number, size and appearance. These observations make a conclusion that all AIDS patients with an esophageal disease should undergo endoscopy with biopsy to obtain a definitive diagnosis.
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