During an earlier multicenter, open-label, randomized controlled trial designed to evaluate the effectiveness of high-dose inhaled ciclesonide in patients with asymptomatic or mild coronavirus disease 2019 (COVID-19), we observed that worsening of shadows on CT without worsening of clinical symptoms was more common with ciclesonide. The present study sought to determine if an association exists between worsening CT shadows and impaired antibody production in patients treated with inhaled ciclesonide. Eighty-nine of the 90 patients in the original study were prospectively enrolled. After exclusions, there were 36 patients each in the ciclesonide and control groups. We analyzed antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein at various time points. Changes in viral load during treatment were compared. There was no significant difference in age, sex, body mass index, background clinical characteristics, or symptoms between the two groups. Although evaluation on day 8 suggested a greater tendency for worsening shadows on CT in the ciclesonide group (p = 0.072), there was no significant difference between them in the ability to produce antibodies (p = 0.379) or the maximum antibody titer during the clinical course. In both groups, worsening CT shadows and higher viral loads were observed on days 1-8, suggesting ciclesonide does not affect clearance of the virus (p = 0.134). High-dose inhaled ciclesonide did not impair production of antibodies against SARS-CoV-2 or affect elimination of the virus, suggesting that this treatment can be used safely in patients with COVID-19 patients who use inhaled steroids for asthma and other diseases.
The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.
Ciprofloxacin (CIP) is frequently detected in the environment and causes the emergence of drug-resistant bacteria. High levels of CIP in the environment are also harmful to humans and animals. Therefore, effective elimination of CIP is required. In this study, plant-based copper nanoparticles (CuNPs) have been fabricated for the purpose of eliminating CIP. Aqueous extracts of 6 plants were compared for their phytochemicals and reducing activity. Among all the extracts, Garcinia mangostana extract (GM) was the most potent with the highest total phenolic compounds, flavonoids, tannins, terpenoids, and reducing activity. CuNPs synthesized using GM (GM-CuNPs) were characterized using UV-VIS spectroscopy and dynamic light scattering. The results showed that the maximum absorption of GM-CuNPs was at 340 nm. The average size of GM-CuNPs is in the nanoscale range of 159.2 ± 61 nm, with a narrow size distribution and a negative zeta potential of – 4.13 ± 6.97 mV. The stability of GM-CuNPs is not solely due to their zeta potential but also phytochemicals in the extract. GM-CuNPs at 25 mM showed the highest efficiency of 95% in removing CIP from aqueous medium pH 6-7 at 25-35°C within 20 min. The results indicated that the electrostatic attraction between the negative charge of GM-CuNPs and the positive charge of CIP controlled the drug adsorption on the nanoparticles. In conclusion, the developed GM-CuNPs have excellent CIP removal efficiency. These synthesized GM-CuNPs are expected to be environmentally friendly for the removal of antibiotics and other drugs.
Lipid metabolism plays an important role in the growth and development of tumors. However, the role of lipid metabolism in gallbladder cancer (GBC) has not been clearly clarified. Here, we demonstrated that fatty acid synthase (FASN), a key enzyme in de novo fatty acid biosynthesis, had upregulated expression in GBC samples both at protein and mRNA levels. Analysis of clinical data indicated the association between elevated FASN expression and poorer histology grades. Furthermore, FASN activity impairment through FASN knockdown or treatment with orlistat resulted in the inhibition of cell proliferation and migration, as well as increased sensitivity to gemcitabine. Both FASN knockdown and orlistat treatment induced cell apoptosis. Mechanistically, impairment of FASN activity suppressed the activation of the PI3K/AKT signaling pathway, which led to increased cell apoptosis and sensitivity to gemcitabine. These findings were also validated through nude mouse xenograft models, thus highlighting the potential of targeting FASN as a clinical treatment strategy. Collectively, the present study underscores the crucial role of FASN in the progression of gallbladder cancer via the PI3K/AKT pathway.
Acute viral pharyngitis is a self-limited disease but the symptoms, a sore throat in particular, can affect one's quality of life. Medicine for symptom relief is the main treatment. Recently, many studies have shown that Andrographis paniculata was efficacious in treating many diseases, including upper respiratory infections. However, adverse reactions to systemic intake are a concern. Therefore, A. paniculata spray is intended to reduce systemic adverse reactions and provide patients with more comfort as its local use. This randomized, double-blind study enrolled 60 adult patients with acute viral pharyngitis. All patients were asked to score the severity of symptoms including a sore throat, difficulty swallowing, and coughing using an 11-point numeric rating scale from 0 to 10. A physical examination was performed to score the severity of erythematous and swollen mucosa using a 0-3 score (0 = no, 1 = mild, 2 = moderate, and 3 = severe). The patients were randomized to receive treatment with either an A. paniculata spray or a positive control chamomile spray. Results revealed a significant reduction in the severity of all signs and symptoms in both groups (p < 0.05). The duration of treatment response in the A. paniculata spray group was 1.9 ± 0.7 days compared to 2.5 ± 1.2 days in the chamomile spray group (p = 0.049). No adverse events were noted in either group. A. paniculata spray is safe and highly efficacious in treating acute viral pharyngitis and can reduce symptoms more rapidly than a positive control spray.
Obesity and diabetes mellitus are associated with increased risk of arterial thrombosis and venous thromboembolism. Tsumura Suzuki Obese Diabetes (TSOD) mice are useful models for elucidating the molecular mechanisms of these diseases. We investigated normoglycemic [Ng]-TSOD mice with a metabolic abnormality that was accompanied by a coagulative and fibrinolytic state with a phenotype that distinctly differed from that of standard TSOD mice. As in TSOD mice, plasminogen activation inhibitor-1 (PAI-1) that inhibits fibrinolysis was substantially augmented in Ng-TSOD mice, suggesting that they are hypofibrinolytic. However, blood clotting parameters were within the normal range in Ng-TSOD mice. These findings indicated that Ng-TSOD mice are novel models with a hypofibrinolytic phenotype that is not associated with hyperglycemia.
This work describes a novel artificial intelligence-based training and monitoring system (AITMS) that was used to control and prevent nosocomial infections (NIs) by improving the skills of donning/removing personal protective equipment (PPE). The AITMS has two working modes, namely an AI-based protective equipment surveillance mode and an AI-based training mode, that were used for routine surveillance and training, respectively. Data revealed that the accuracy rate of donning/removing PPE improved as a result of the AITMS. Interestingly, the frequency of NIs decreased with the use of the AITMS. This study suggested the key role of using PPE in controlling and preventing NIs. Data preliminarily proved that appropriate donning/removing PPE may help to reduce the risk of NIs. In addition, the newest computerized technologies, such as AI, have proven to be useful in controlling and preventing NIs. These findings should helpful to formulate a better strategy against NIs in the future.
Disinfection of dental unit waterlines (DUWLs) plays a key role in control and prevention of nosocomial infection in a dental clinic. The most conventional disinfectant is hydrogen peroxide (H2O2), while chlorine dioxide (ClO2) has been considered however was limited by the "activation" procedures. With the availability of commercialized stable ClO2 solution (free of activation), direct application of ClO2 in the dental practice became possible. This study was designed to compare the disinfecting effects of stable 5 ppm of ClO2 solution with conventional 0.24% of H2O2 on DUWLs in dental practice. Studies of colony-forming units (CFUs), confocal laser scanning microscopy (CLSM) and scanning electron microscope (SEM) were employed for evaluation. In CFUs studies, we found that the efficiency of ClO2 was no less than those of H2O2. In the morphological studies, the stronger disinfecting effects of ClO2 was verified by both CLSM and SEM studies for removal and prevention of biofilm. Importantly, ClO2 solution achieved a better disinfecting efficiency not only at the surface of bacterial biofilm, but also, it has penetrating effects, presented disinfecting effects from the surface to the bottom of the biofilm. This pilot study provided evidence regarding the efficiency of stable ClO2 solution on disinfection of DUWLs in the dental practice setting. Application of stable ClO2 solution in dental practice is therefore become possible.
Structure-based virtual screening plays a critical role in drug discovery. However, numerous docking programs, such as AutoDock Vina and Glide, are time-consuming due to the necessity of generating numerous molecular conformations and executing steps like scoring, ranking, and refinement for the ligand-receptor complexes. Consequently, achieving rapid and reliable virtual screening remains a noteworthy challenge. Recently, a team of researchers from Massachusetts Institute of Technology, led by Stärk et al., developed an SE(3)-equivariant geometric deep learning based protein-ligand binding prediction approach, EQUIBIND. In comparison to conventional docking methods, EQUIBIND has the capacity to predict the binding modes of small molecules with target proteins rapidly and precisely. It presents an innovative resolution for high-throughput screening of drug-like compounds.
Complete chromosome 9 trisomy (T9) is a rare and fatal chromosomal disorder. We performed non-invasive prenatal testing (NIPT) in a patient with threatened abortion symptoms and found that the fetal was at risk for complete chromosome 9 trisomy. This shows that NIPT has certain accuracy in detecting trisomy of chromosome 9, which provide options for prenatal diagnosis of rare chromosomal abnormalities.