Search Results (88,445)

The COVID-19 pandemic and other infectious diseases continue to threaten public health, particularly in densely populated informal settlements. Effective hand hygiene, supported by alcohol-based hand sanitizers (ABHS), plays a critical role in preventing disease transmission. This study assessed the quality, safety, and compliance of ABHS used in informal settlements around Cape Town. A total of 78 samples were collected from spaza shops, with 72 analyzed using gas chromatography with flame ionization detection. The results showed that 76% of ethanol-based sanitizers met compliance standards, while 24% did not. Isopropanol compliance (≥70%) was only observed in 36% of samples, with 64% failing to meet Centers for Disease Control and Prevention (CDC) guidelines. Overall, 74% of hand sanitizers complied with recommended alcohol concentrations by the U.S. Food and Drug Administration (FDA) and CDC, while 26% posed a health risk due to non-compliance. These findings emphasize the urgent need for stricter regulation and public education to ensure effective hand sanitizers are used, thereby reducing infection risks in vulnerable populations. The study aims to inform public health policies and improve regulatory standards. Full article

Background/Objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD). Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L. Results: A total of 8318 patients were included, with 6185 in CKD stages 1–2 and 2133 in stages 3a–5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001). Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy. Full article

Calcium phosphate bone cement (CPC) is a popular material for bone remodeling, and nanohydroxyapatite (nHA) represents a breakthrough that has a wide range of clinical applications. During the early stages of bone repair, antibacterial and angiogenesis effects are essential to remodel new bone tissues. In this study, an antibacterial effect was achieved by incorporating Cu²⁺-doped nano-hydroxyapatite (Cu–nHA) synthesized through hydrothermal methods into CPC, and the impact of various amounts of Cu–nHA addition on the antibacterial and mechanical properties of CPC hybridization was evaluated. Moreover, the effects of Cu–nHA/CPC composites on the proliferation and mineralization of mouse progenitor osteoblastic cells (D1 cells) were characterized; the cell migration and angiogenesis ability of vascular endothelial cells (HUVECs) were also studied. Results indicated that incorporating 5 wt.% and 10 wt.% Cu–nHA into CPC led to a practical short-term antibacterial effect on S. aureus but not on E. coli. These Cu–nHA/CPC slurries remained injectable, anti-disintegrative, and non-toxic. Furthermore, compared with pure CPC, these Cu–nHA/CPC slurries demonstrated positive effects on D1 cells, resulting in better proliferation and mineralization. In addition, these Cu–nHA/CPC slurries were more effective in promoting the migration and angiogenesis of HUVECs. These findings indicate that 10 wt.% Cu–nHA/CPC has great application potential in bone regeneration. Full article

Background/Objective: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use of benzylpenicillin in OPAT requires special consideration because of its limited stability at elevated temperatures. Methods: We tested the benzylpenicillin stability, pH, and degradation of products in elastomeric pumps at different concentrations in saline and in buffered solution containing sodium citrate during a prolonged storage and at high temperatures (seven days at 2–8 °C followed by 24 h at 37 °C). Additionally, drug concentrations during intermittent bolus infusion and during OPAT were determined in five patients. The concentrations and degradation products of benzylpenicillin were measured using liquid chromatography mass spectrometry (LC-MS/MS). Results: Unbuffered benzylpenicillin solutions that were already degraded during refrigerator storage and analyte concentration were not measurable after 8 days. The stability of the buffered solutions was acceptable at all three of the tested concentrations (97.6 ± 1.3%, 96.3 ± 0.8%, and 94.9 ± 1.1% for 10 Mio IU, 20 Mio IU, and 40 Mio IU of benzylpenicillin). The stability was influenced by benzylpenicillin concentration, and several breakdown products were identified. Benzylpenicillin concentrations were measured in five patients during OPAT and ranged from 7.2 to 60 mg/L. Conclusions: Benzylpenicillin buffered with sodium citrate is a safe and convenient option for use in continuous infusions during OPAT and should be favored over broad-spectrum antibiotics. Therapeutic drug monitoring data indicate sufficient to high plasma levels when patients received benzylpenicillin as continuous infusions. Full article

Background: To elucidate the effects of local anesthetic agents (LAs), guinea pigs are used in pharmacological education. Herein, we aimed to develop a simulator for LAs. Previously, we developed a statistical model to simulate the LAs’ effects, and we estimated their parameters (mean [μ] and logarithm of standard deviation [logσ]) based on the results of animal experiments. The results of the Monte Carlo simulation were similar to those from the animal experiments. However, the drug parameter values widely varied among individuals, because this simulation did not consider correlations among parameters. Method: In this study, we set the correlations among these parameters, and we performed simulations using Monte Carlo simulation. Results: Weakly negative correlations were observed between μ and logσ (rμ−logσ). In contrast, weakly positive correlations were observed among μ (rμ) and among logσ (rlogσ). In the Monte Carlo simulation, the variability in duration was significant for small rμ−logσ values, and the correlation for the duration between two drugs was significant for large rμ and rlogσ values. When parameters were generated considering the correlation among the parameters, the correlation of the duration among the drugs became larger. Conclusions: These results suggest that parameter generation considering the correlation among parameters is important to reproduce the results of animal experiments in simulations. Full article

Aging is the major risk factor for Alzheimer’s disease (AD). In the aged brain, myelin debris accumulates and is cleared by microglia. Phagocytosed myelin debris increases neutral lipid droplet content in microglia. Neutral lipids include cholesteryl esters (CE) and triacylglycerol (TAG). To examine the effects of myelin debris on neutral lipid content in microglia, we added myelin debris to human HMC3 and mouse N9 cells. The results obtained when using ³H-oleate as a precursor in intact cells reveal that myelin debris significantly increases the biosynthesis of CE but not TAG. Mass analyses have shown that myelin debris increases both CE and TAG. The increase in CE biosynthesis was abolished using inhibitors of the cholesterol storage enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1/SOAT1). ACAT1 inhibitors are promising drug candidates for AD treatment. In myelin debris-loaded microglia, treatment with two different ACAT1 inhibitors, K604 and F12511, increased the mRNA and protein content of ATP-binding cassette subfamily A1 (ABCA1), a protein that is located at the plasma membrane and which controls cellular cholesterol disposal. The effect of the ACAT1 inhibitor on ABCA1 was abolished by preincubating cells with the liver X receptor (LXR) antagonist GSK2033. We conclude that ACAT1 inhibitors prevent the accumulation of cholesterol and CE in myelin debris-treated microglia by activating ABCA1 gene expression via the LXR pathway. Full article

With the advantages of a high specificity, a long half-life, and a high safety, the use of antibody biologic drugs, including camrelizumab, has been rapidly increasing in clinical practice. Camrelizumab, an immune checkpoint inhibitor and humanized monoclonal antibody, is used to treat several advanced solid cancers. Measuring its concentration supports personalized dosage adjustments, influences treatment decisions for patients, strengthens the control of disease activity through therapeutic drug monitoring, and helps evaluate and prevent drug interactions in combination therapy. Because antibodies are present in complex biological matrices, quantifying monoclonal antibody drugs is challenging, and must rely on precise, selective, and reliable analytical methods. In this study, a quadrupole time-of-flight mass spectrometry TripleTOF 6600+ (AB SCIEX, Framingham, MA, USA) system equipped with a Turbo V ion source was used for the qualitative analysis of monoclonal antibodies using the data-dependent acquisition (IDA) MS/MS mode, followed by quantitative analysis using a targeted MRMHR workflow. This method showed a good linear relationship within the range of 4–160 μg/mL, with a correlation coefficient of R² ≥ 0.996. It demonstrated an acceptable accuracy (88.95–101.18%) and precision (≤15%). Furthermore, the lower limit of quantification was found to be 4 μg/mL, with the lowest detection limit of 0.3217 μg/mL, indicating that this method is rapid, accurate, and reliable for the quantitative analysis of camrelizumab in human serum. Full article

Sprinkle formulations represent an interesting genre of medicinal products. A frequent problem, however, is the need to mask the unpleasant taste of these drug substances. In the present work, we propose the use of a novel sensor array based on solid-state ion-selective electrodes to evaluate the taste-masking efficiency of rosuvastatin (ROS) sprinkle formulations. Eight Multiple Unit Pellet Systems (MUPSs) were analyzed at two different doses (API_50) and (API_10), as well as pure Active Pharmaceutical Ingredient (API) as a bitter standard. Calcium phosphate-based starter pellets were coated with the mixture containing rosuvastatin. Some of them were additionally coated with hydroxypropyl methylcellulose, which was intended to separate the bitter substance and prevent it from coming into contact with the taste buds. The sensor array consisted of 16 prepared sensors with a polymer membrane that had a different selectivity towards rosuvastatin calcium. The main analytical parameters (sensitivity, selectivity, response time, pH dependence of potential, drift of potential, lifetime) of the constructed ion-selective electrodes sensitive for rosuvastatin were determined. The signals from the sensors array recorded during the experiments were processed using Principal Component Analysis (PCA). The results obtained, i.e., the chemical images of the pharmaceutical samples, indicated that the electronic tongue composed of the developed solid-state electrodes provided respective attributes as sensor signals, enabling both of various kinds of ROS pellets to be distinguished and their similarity to ROS bitterness standards to be tested. Full article

Synovial sarcoma (SS) is one of the most common types of pediatric soft tissue sarcoma (STS) being far less frequent in adults. This STS type is characterized by one specific chromosomal translocation SS18-SSX and the associated changes in signaling. However, other genetic and epigenetic abnormalities in SS do not necessarily include SS18-SSX-related events, but abnormalities are more sporadic and do not correlate well with the prognosis and response to therapy. Currently, targeted therapy for synovial sarcoma includes a limited range of drugs, and surgical resection is the mainstay treatment for localized cancer with adjuvant or neoadjuvant chemotherapy and radiotherapy. Understanding the molecular characteristics of synovial sarcoma subtypes is becoming increasingly important for detecting new potential targets and developing innovative therapies. Novel approaches to treating synovial sarcoma include immune-based therapies (such as TCR-T cell therapy to NY-ESO-1, MAGE4, PRAME or using immune checkpoint inhibitors), epigenetic modifiers (HDAC inhibitors, EZH2 inhibitors, BRD disruptors), as well as novel or repurposed receptor tyrosine kinase inhibitors. In the presented review, we aimed to summarize the genetic and epigenetic landscape of SS as well as to find out the potential niches for the development of novel diagnostics and therapies. Full article

Fetal growth restriction (FGR) is a common complication of pregnancy, associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiometabolic diseases later in life. There is currently no effective approach to prevent or treat FGR, despite numerous animal and human studies assessing substances likely to improve fetal growth. Phosphodiesterase (PDE) inhibitors appeared as promising drugs to improve FGR management. However, to date, studies have led to somewhat disappointing or controversial results. In this Opinion article, we would like to draw attention to the need to consider the biological sex and the relative reactivity of human umbilical vein and arteries when developing therapeutic interventions to improve human umbilical circulation using PDE inhibitors. Indeed, we suspect that fetal sex, vessel type and the presence of FGR may influence subcellular compartmentation, which could jeopardize beneficial effects of PDE inhibitors. Full article

Colorectal cancer (CRC) has become a prevalent and deadly malignancy over the years. Drug resistance remains a major challenge in CRC treatment, significantly affecting patient survival rates. Obesity is a key risk factor for CRC development, and accumulating evidence indicates that increased secretion of adipokines, including Visfatin, under obese conditions contributes to the development of resistance in CRC to various therapeutic methods. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family, which activates the EGF receptor (EGFR), influencing multiple tumorigenic characteristics of cancers. Abnormal expression levels of AREG in cancer cells have been associated with resistance to anti-EGFR therapy in patients. However, it remains unclear whether this abnormal expression also impacts CRC resistance to other chemotherapeutic drugs. The aim of this study is to examine whether AREG expression levels could be affected in CRC cells under Visfatin stimulation, thereby initiating the development of resistance to 5-fluororacil (5-FU). Through our results, we found that Visfatin indeed increases AREG expression, reducing the sensitivity of HCT-116 CRC cells to 5-FU cytotoxicity. Moreover, AREG upregulation is regulated by STAT3-CREB transcription factors activated by JNK1/2 and p38 signaling. This study highlights the significant role of AREG upregulation in CRC cells in initiating chemotherapeutic resistance to 5-FU under Visfatin stimulation. These findings provide a deeper understanding of drug resistance development in CRC under obese conditions and offer new insights into the correlation between an abnormal increase in AREG levels and the development of 5-FU-resistance in CRC cells, which should be considered in future clinical applications. Full article

Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI’s applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI’s transformative impact on the pharmaceutical industry and its broader implications for healthcare. Full article

Arbuscular mycorrhizal fungi (AMF) and the antioxidant germanium (Ge) are promising tools for boosting bioactive compound synthesis and producing healthier foods. However, their combined effect remains unexplored. This study demonstrates the synergistic impact of AMF and Ge on the growth, metabolite accumulation, biological activities, and nutritional qualities of Spinacia oleracea L. (spinach), a globally significant leafy vegetable. Individually, Ge and AMF increased biomass by 68.1% and 22.7%, respectively, while their combined effect led to an 86.3% increase. AMF and Ge also improved proximate composition, with AMF–Ge interaction enhancing crude fiber and mineral content (p < 0.05). Interestingly, AMF enhanced photosynthesis-related parameters (e.g., total chlorophyll) in Ge treated plants, which in turn increased carbohydrate accumulation. This accumulation could provide a route for the biosynthesis of amino acids, organic acids, and fatty acids, as evidenced by increased essential amino acid and organic acid levels. Consistently, the activity of key enzymes involved in amino acids biosynthesis (e.g., glutamine synthase (GS), methionine biosynthase (MS), lysine biosynthase (LS)) showed significant increments. Furthermore, AMF improved fatty acid levels, particularly unsaturated fatty acids in Ge-treated plants compared to the control. In addition, increased phenylalanine provided a precursor for the production of antioxidants (e.g., phenols and flavonoids), through the action of the enzyme phenylalanine ammonia-lyase (PAL), resulting in improved antioxidant activity gains as indicated by FRAP, ABTS, and DPPH assays. This study is the first to show that Ge enhances the beneficial effect of AMF on spinach, improving growth and nutritional quality, with promising implications for agricultural practices. Full article

Biotechnological processes are essential for developing economies that aim to stand out in future markets. The use of bioreactors is one of the most important unit operations of biotechnological processes, and real-time monitoring of bioreactors is essential to ensure precise bioprocess control. This review presents different types of bioreactors, sensors, and applications in other sectors. Bioreactors, controlled systems for cultivating microorganisms and cells, are essential tools in various fields, from scientific research to industrial production. The use of a variety of sensors is critical for accurate, real-time monitoring, early problem detection, reproducibility, cost reduction, and increased efficiency. These benefits are being realized in numerous applications, including biofuel production, bioremediation and leaching processes, tissue engineering, and drug manufacturing. Innovations in bioreactor technology are expanding opportunities for a more sustainable and healthier future. By developing new types of bioreactors, integrating advanced sensors, and exploring promising applications, bioreactors are playing a key role in addressing global challenges and sustainably advancing science and technology. Full article

The primary aim of this research was to identify the structural characteristics of three newly derived procyanidins from cold plasma-treated (–)-epicatechin, known for their anti-inflammatory properties. The newly generated compounds were isolated through column chromatography, and their chemical structures were elucidated through spectroscopic data analyses, including both one-dimensional and two-dimensional nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Furthermore, their absolute configurations were determined via circular dichroism (CD) spectroscopy. The inhibitory activity of the isolated compounds on nitric oxide (NO) production and expression levels of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages was evaluated. Three new procyanidins—methylenetrisepicatechin (2), isomethylenetrisepicatechin (3), and methylenebisepicatechin (4)—along with two reported dimeric flavan-3-ols (5 and 6), were identified from plasma-treated (–)-epicatechin (1). The unique oligomerized products 2 and 3 linked by methylene bridges significantly suppressed both NO production and iNOS expression, demonstrating higher anti-inflammatory activities in LPS-stimulated RAW 264.7 cells compared with the parent compound. The newly oligomerized procyanidins have potential applications in the treatment of inflammatory diseases owing to their significant anti-inflammatory properties. Full article