Search Results (712)

Raw milk and traditional fermented foods such as artisanal cheese represent a natural source of lactic acid bacteria (LAB). They can produce antimicrobial compounds, such as bacteriocins and lactic acid, which may be exploited in dairy biopreservation. This study aimed to conduct a systematic review and meta-analysis to synthesize the inhibition diameter (ID) of LAB against L. monocytogenes, S. aureus, and Salmonella spp. Literature electronic searches were performed on PubMed, Scopus, and Web of Science, to identify articles that reported data on in-vitro antimicrobial activity by LAB isolated from dairy foods. A total of 1665 papers were retrieved, and 20 primary studies were selected according to the selection criteria, of which 397 observations were extracted. Random-effects meta-regression models were employed to describe the effects of LAB genus, pathogen concentration, susceptibility method, incubation time, inoculation volume, agar type and pH on the IDs for L. monocytogens, S. aureus, and Salmonella spp. L. monocytogens was the most susceptible pathogen (p < 0.05) to the LAB effects, followed by S. aureus and Salmonella spp. As a whole, LAB from the Lacticaseibacillus genus were the most effective (p < 0.05) in inhibiting L. monocytogens (21.49 ± 2.654 mm), followed by S. aureus (21.06 ± 2.056 mm). Salmonella spp. presented higher (p < 0.05) susceptibility to Lactobacillus genus (19.93 ± 2.456 mm). From the results, a general trend could be observed for the well-diffusion method to produce higher (p < 0.05) ID estimates than the spot and disk methods (30.73 ± 2.530 mm vs. 21.98 ± 1.309 mm vs. 13.39 ± 1.403 mm for L. monocytogenes; 22.37 ± 1.073 mm vs. 14.91 ± 2.312 mm vs. 20.30 ± 2.319 mm for Salmonella spp.), respectively. Among the tested moderators, the pathogen’s inoculum concentration, the in vitro susceptibility assay itself, incubation time and inoculation volume on agar are determinant parameters to be looked at when designing a robust and reproducible experimental plan. The in vitro results reinforced that LAB can be useful in controlling the development of pathogenic bacteria frequently found in the dairy industry. Full article

Background: Carbamazepine (CBZ) is a Biopharmaceutical Classification System (BCS) class II drug, that is practically insoluble in water, influencing the oral bioavailability. Polyols are highly hydrophilic crystalline carriers studied for their success in developing solid dispersions (SDs) for improved solubility and dissolution rate. Polyols are generally regarded as safe (GRAS) and maltitol (MAL), xylitol (XYL) and sorbitol (SOR) are among the approved polyols for market use. While xylitol (XYL) and sorbitol, have shown promise in improving the solubility and dissolution rates of poorly soluble drugs, their full potential in the context of improving the solubility of carbamazepine have not been thoroughly investigated. To the best of our knowledge, maltitol (MAL) was not studied previously as a carrier for preparing SDs. Hence, the purpose of this study was to investigate their use in the preparation of CBZ SDs by the fusion method. Methods: CBZ-polyol SDs were prepared in varying molar ratios (2:1, 1:1 and 1:2) and characterised for solid-state nature, solubility and in-vitro dissolution rate. Results: Solid-state characterisation of the CBZ-polyol SDs revealed the existence of the SDs as continuous glass suspensions with fine CBZ crystallites suspended in the amorphous polyol carriers. Among the polyols studied, XYL exhibited good miscibility with CBZ and showed significant improvement in the solubility and dissolution rate. The prepared SDs showed a 2 to 6-folds increase in CBZ solubility and 1.4 to 1.9-folds increase in dissolution rate in comparison with pure CBZ. Conclusions: The study explains the possible use of polyols (XYL and SOR) based SDs of BCS Class II drugs with good glass forming ability for enhanced solubility and dissolution. Full article

Background: Recently, the demand for esthetic restorations has grown dramatically and extended into the pediatric population. The prefabricated zirconia crowns (PZCs) and custom-made zirconia crowns (CZCs) are new esthetic options in pediatric dentistry. However, they are still inadequately tested for use in children. Aim: To determine the fracture resistance and failure mode of the PZC in comparison to the CZC. Materials and Methods: In this in-vitro study, thirty cobalt-chromium dies were fabricated by scanning the negative replica of a prefabricated lower first permanent molar zirconia crown. CZCs were designed and milled using two different zirconia brands: Ceramill Zolid-FX (FX) and the Highly-Translucent (HT) zirconia. Dies were randomly assigned to receive either a PZC or a CZC (n = 10 in each group). All crowns were cemented on their respective dies using glass ionomer cement. Following artificial aging, all specimens were loaded to failure. Fracture mode analysis was performed. One-way ANOVA and Bonferroni post-hoc test were used for multiple comparisons across the groups. The significant level was set at p ≤ 0.05. Results: HT zirconia had a significantly higher fracture load compared to other groups (p < 0.05). The mean fracture resistance values were: (3087 ± 385) N for HT zirconia, (2633 ± 300) N for PZCs, and (2483 ± 381) N for FX, with no statistically significant difference in fracture strengths between PZCs and FX. Conclusions: HT zirconia crowns showed the highest fracture resistance amongst all groups. The fracture loads of tested crowns exceeded the maximum posterior biteforce. When placed in permanent molars, PZC are expected to perform well under masticatory forces in children. Full article

Autologous blood centrifugation produces various forms of platelet concentrates widely used in tissue regenerative therapies due to their high concentrations of growth factors and abundance of autologous cells. Advanced Platelet-Rich Fibrin (A-PRF), introduced as a low-speed centrifugation product, contains an even higher concentration of growth factors, a greater number of cells, and a looser fibrin clot structure compared to previous Leukocyte and Platelet-Rich Fibrin (L-PRF). This study aims to assess the potential of A-PRF as a local delivery system for antibiotics. Different concentrations (0.5 mg/mL, 0.25 mg/mL, and 0.125 mg/mL) of injectable amoxicillin (AMX) and metronidazole (MTZ) were preliminarily tested for their impact on A-PRF clot formation, with 0.5 mg/mL selected for subsequent experiments. Blood samples from healthy volunteers were supplemented with antibiotics and centrifuged to form clots. Antibiotic-enriched A-PRF clots were immersed in phosphate-buffered saline (1x PBS) and analyzed at 24 h, 72 h, 7 days, and 14 days. AMX showed a consistent release (mean: 19.9 ± 4.8 ng/mL at 24 h) over 14 days, while MTZ demonstrated greater variability (mean: 12.8 ± 4.5 ng/mL at 24 h). AMX release remained constant over the 14-day period, with no significant variations among patients. In contrast, MTZ displayed a progressively lower release over time. Microbiological analysis revealed bacterial growth inhibition zones for Fusobacterium nucleatum (AMX: 23 mm, MTZ: 28 mm) and Prevotella intermedia (AMX: 34 mm, MTZ: 30 mm) at 24 h. These findings suggest that A-PRF can act as an effective local antibiotic delivery system, maintaining sustained antimicrobial activity and potentially reducing the need for systemic antibiotics. Full article

Introduction: Intra-articular injections, commonly used in osteoarthritis treatment, are debated due to their potential link to septic arthritis, though its incidence remains low. Lidocaine, used as a “carrier” for therapeutic substances like hyaluronan or triamcinolone, has pain-relieving and antimicrobial properties. This study investigates the concentration-dependent antimicrobial effects of lidocaine in combination with hyaluronan and triamcinolone in both standard and synovial fluid cultures. Methods: The antimicrobial efficacy of lidocaine against Staphylococcus aureus was investigated, with variations in bacterial and lidocaine concentrations. Bacterial growth was monitored using a UV/VIS spectrometer at 600 nm. Lidocaine solutions of 1% and 2% were tested, both alone and in combination with hyaluronic acid or Triam40, in tryptic soy broth (TSB), to reflect knee joint applications. The groups included pure lidocaine (L), Triam (T), hyaluronan (H), and combinations (LT, LH, TH, LTH) with 1% or 2% lidocaine. A bacterial inoculum of 300 CFU/mL was used, and samples were incubated for 12 and 24 h. Additional tests were conducted on Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA), as well as on S. aureus in human synovial fluid. Results: Lidocaine showed a concentration-dependent antimicrobial effect, with greater inhibition at higher concentrations and lower bacterial densities. All lidocaine-containing combinations significantly reduced the bacterial levels of S. aureus in TSB. Similar results were seen for S. epidermidis and MRSA, with notable inhibition in synovial fluid after 12 h, especially with 2% lidocaine. Conclusions: Lidocaine exhibits dose-dependent antimicrobial effects against key pathogens responsible for septic arthritis. Its combination with Triam40 and hyaluronan may reduce the risk of septic arthritis, supporting its clinical relevance. Full article

Objectives: The development of novel long-acting injectables for local anesthetics is necessary to effectively manage the acute postoperative pain. The aim of this study was to prepare an injectable oil-based formulation of ropivacaine (ROP) prodrug (ropivacaine stearoxil, ROP-ST) and to investigate the pharmacokinetics and pharmacodynamics after injectable administration. Methods: A novel N-acyloxymethyl prodrug of ROP, i.e., ROP-ST, was synthesized and its physicochemical properties such as log P, solubility and stability characterized. A soybean oil-based depot of ROP-ST was prepared, and the in-vitro release of ROP-ST was evaluated using an “inverted-cup” method. Pharmacokinetic profiles and tissue retention properties were investigated after intramuscular administration of the formulation in rats. The analgesic efficacy was assessed via a von Frey monofilaments test by measuring the paw withdrawal thresholds. Results: The structure of ROP-ST was ascertained with clear ¹H NMR assignment and accurate mass-to-charge ratio. The high Log P value of ROP-ST (9.16) demonstrated extremely low aqueous solubility, but the prodrug is biolabile when in contact with plasma or liver esterase. Intramuscular injection of ROP-ST oil solution in rats provided a significantly higher mean residence time without a very clear plasma peak of ROP. In a postoperative pain model of rats, the injection of ROP-ST oil solution into the vicinity of the sciatic nerve in the right ankle effectively controlled the postoperative pain for at least 72 h. Conclusions: The injectable oil-based depot formulation of N-acyloxymethyl prodrug of ROP may provide a new opportunity of long-acting local analgesia for postoperative pain. Full article

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance. Here, we provide an in-depth and detailed protocol to successfully modify the gene expression of HGSOC-PDOs by lentiviral transduction. As an example, we validate our protocol and create a stable knockdown of the MACC1 oncogene with an efficacy of ≥72% in two HGSOC-PDO lines, which remained stable for >3 months in culture. Moreover, we explain step-by-step the sample preparation for the validation procedures on transcriptional (qPCR) and protein (Western Blot) levels. Sustained downregulation of specific genes by lentiviral transduction enables the analysis of the resulting phenotypic and morphological changes. It serves as a valuable in-vitro model to study the mechanisms of ovarian cancer pathogenesis and allows for the evaluation of therapeutic approaches. Full article

Background/Objectives: Skin wrinkles result from a myriad of multifaceted processes involving intrinsic and extrinsic aging. To combat this effect, plant stem cells offer a renewable and eco-friendly source for various industries, including cosmeceuticals. Salvia miltiorrhiza (SM), which contains the bioactive compound Rosmarinic acid (RA) and has been proposed for its anti-wrinkle effect. Methods: In the present study, calli from SM were cultured and Quality by Design (QbD) was implemented to investigate the effect of different types and concentrations of elicitors; jasmonic acid (JA) and salicylic acid (SA). Both raised RA levels yet, jasmonic acid (50 µM) has resulted in the highest yield for RA, at 16 mg/g. A nanofiber patch was prepared and characterized in-vitro by the release percentage, drug content, swelling degree, scanning electron microscope, and surface roughness. Then, the anti-wrinkle effect of the patch was tested in a UV wrinkle-induced mouse model. Results: Interestingly, after treatment, there were visibly fewer wrinkles, and the skin was softer than in the untreated control group. This study suggests that the treatment exerted its effect through the Nrf2/Keap1 pathway, which plays a crucial role in cellular antioxidant protective processes. By activating this pathway through boosting Nrf2 and diminishing Keap1 cellular content, the nanofiber patch enhances the production of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, enhancesglutathione, and reduces the skin lipid peroxidation, collectively indicating enhanced skin quality. Conclusions: In conclusion, this study highlights the importance of this formula as an anti-wrinkle treatment, and future clinical studies are recommended to further unveil the potential of this formula. Full article

Triptolide (TP) is a diterpenoid compound extracted from the traditional Chinese medicinal herb Tripterygium wilfordii. It has antitumor and anti-inflammatory effects and stimulates immunity. However, its serious side effects, especially reproductive toxicity, limit its clinical application. This study employed a testicular injury model established by intraperitoneally injecting TP (0.2 mg/kg) in C57BL/6J male mice (age = 7–8 weeks) for 14 days. The control and TP mice’s testicular tissues were subjected to transcriptome sequencing to assess potential testicular damage mechanisms. Based on the transcriptome sequencing results and relevant literature reports, further experiments were performed. In addition, to alleviate triptolide-induced testicular damage, we treated the mice with N-acetyl-L-cysteine (NAC). The acquired data revealed that compared with the control mice, the TP-treated mice’s testes indicated severe damage. Transcriptome sequencing identified differentially expressed genes that showed enrichment in cell differentiation, apoptotic process, cell cycle, glutathione (GSH) metabolism, and the p53 signaling pathway. Furthermore, TUNEL assays and Western blot analysis showed that in the TP mice’s testicular tissues, the spermatocytes had mitochondrial pathway apoptosis as well as abnormal mitochondrial morphology and structure. Triptolide induces oxidative stress in testicular tissue by enhancing pro-oxidative systems and inhibiting antioxidant systems. NAC reduced testicular damage and apoptosis by alleviating TP-induced oxidative stress. This study also employed a GC2 cell line for in-vitro analyses, and the results were consistent with the in vivo experiments. This study provides evidence for alleviating TP’s adverse effects on the male reproductive system for better clinical application. Full article

Female fertility and reproductive system disorders are influenced by a complex interplay of biological, physiological, and environmental factors. Minerals have emerged as crucial yet often overlooked elements that impact fertility and the prevalence of reproductive system disorders. Background/Objectives: This review aims to provide a comprehensive overview of the multifaceted role of minerals in female fertility, focusing on key areas such as oocyte quality, ovulation, embryo development, oxidative stress, miscarriage, hormonal regulation, environmental exposure, and in-vitro fertilization (IVF) outcomes. Methods: A systematic review was conducted, focusing on randomized controlled trials (RCTs), prospective cohort studies, case-control studies, nested case-control, and observational studies examining mineral supplementation and nutrition in women planning pregnancy or utilizing assisted reproduction technologies (ARTs). Relevant literature was sourced from multiple electronic databases, including PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library, using keywords related to minerals and female fertility. The quality of studies was assessed using the Newcastle–Ottawa Scale (NCO) for non-randomized studies and the Risk of Bias (RoB) tool for RCTs. This systematic review has been registered on PROSPERO (registration number is CDR 42024547656). Results: From an initial pool of 20,830 records, 39 articles met the inclusion criteria and were analyzed. The studies addressed various reproductive outcomes influenced by minerals: embryo development, oocyte quality, oxidative stress, miscarriage, hormonal regulation, IVF outcomes, environmental exposure, and minerals as biomarkers. The analysis revealed that minerals like selenium, zinc, and copper are essential for maintaining reproductive health, while exposure to toxic metals such as cadmium and lead is detrimental. Conclusions: This review highlights the crucial role of both mineral supplementation and serum mineral status in female fertility. The findings provide key insights for clinicians to improve reproductive health through targeted mineral intake and monitoring. Further research is needed to refine guidelines for supplementation and serum levels in women with fertility issues. Full article

Bacterial keratitis caused by Pseudomonas aeruginosa is indeed a serious concern due to its potential to cause blindness and its resistance to antibiotics, partly attributed to biofilm formation and cytotoxicity to the cornea. The present study uses a meta-analysis of a transcriptomics dataset to identify important genes and pathways in biofilm formation of P. aeruginosa induced keratitis. By combining data from several studies, meta-analysis can enhance statistical power and robustness, enabling the identification of 83 differentially expressed candidate genes, including fis that could serve as therapeutic targets. The approach of combining meta-analysis with virtual screening and in vitro methods provides a comprehensive strategy for identifying potential target genes and pathways crucial for bacterial biofilm formation and development anti-biofilm medications against P. aeruginosa infections. The study identified 83 candidate genes that exhibited differential expression in the biofilm state, with fis proposed as an ideal target for therapy for P. aeruginosa biofilm formation. These techniques, meta-analysis, virtual screening, and invitro methods were used in combination to diagnostically identify these genes, which play a significant role in biofilms. This finding has highlighted a hallmark target list for P. aeruginosa anti-biofilm potential treatments. Full article

Background: Surface treatment of the intaglio surface of zirconia is important for bonding. However, it could affect the strength of the materials. The purpose of this study is to compare the effect of laser, etching, and air abrasion surface treatment methods to a control group on the flexural strength of three zirconia materials with two different thicknesses. (1) Methods: A total of 120 disks were divided into three groups according to the type of zirconia and the ceramic thickness. Then, according to the surface treatment method, the groups were divided into four subdivisions. The change in the microstructure of the ceramic material was investigated through Scanning Electron Microscope (EVO LS10, Carl Zeiss SMT Ltd. Oberkochen, Germany). Phase identification was performed using an X-ray diffraction device (XRD; Ultimate IV X-ray Diffractometer, Rigaku Inc., Tokyo, Japan). The flexural strength was assessed with a biaxial flexural strength test in a universal testing machine. Data were analyzed using SPSS Software (SPSS version 26.0.Armonk, NY: IBM Corp). A three-way ANOVA and a post hoc Dunnett T3 test were employed to evaluate the effect of the yttria concentration, thickness, and surface treatment on the flexural strength of zirconia (α = 0.05). (2) Results: At 0.8 mm thickness, air abrasion significantly increased the flexural strength of 3Y-TZP (1130.6 ± 171.3 MPa) and 4Y-TZP (872 ± 108.6 MPa). However, air abrasion significantly decreased the flexural strength of 5Y-TZP materials (373 ± 46.8 MPa). Laser irradiation significantly decreased the flexural strength of 5Y-TZP (347 ± 50.3 MPa), while etching significantly decreased the flexural strength of both 3Y-TZP (530 ± 48.8) and 4Y-TZP (457.1 ± 57.3). When the thickness increased to 1 mm, air abrasion continued to significantly decrease the flexural strength of 5Y-TZP materials. (3) Conclusions: There was a negative effect of surface treatment on the flexural strength at 0.8 mm thickness rather than at 1 mm thickness. Air abrasion enhances the flexural strength of 3Y-TZP and 4Y-TZP materials but significantly reduces the flexural strength of 5Y-TZP materials. Zircos-E etching and Er:YAG surface treatment methods did not significantly reduce the flexural strength of 5Y-TZP materials at 1 mm thickness and can be recommended as an alternative surface treatment for 5Y-TZP materials. Full article

Background: This study aimed to optimize the coating process of Omega-3 fatty acid (OM3-FA) mini soft capsules containing the active pharmaceutical ingredients (APIs) pitavastatin and ezetimibe using near-infrared (NIR) spectroscopy for in-process monitoring. Cardiovascular disease treatments benefit from combining OM3-FA with lipid-lowering agents, but formulating such combinations in mini soft capsules presents challenges in maintaining stability and mechanical integrity. Methods: The coating process was developed using a pan coater and real-time NIR monitoring to ensure uniformity and quality. NIR spectroscopy enabled precise control of coating thickness, ensuring consistent drug distribution across the capsule surface. Results: The optimized process minimized OM3-FA oxidation and preserved the mechanical integrity of the capsules, as confirmed by texture analysis and in-vitro dissolution testing. This integration of NIR spectroscopy as a process analytical technology (PAT) significantly improved coating quality control, resulting in a stable and effective combination therapy for pitavastatin and ezetimibe in a mini soft capsule form. Conclusion: This approach offers an efficient solution for enhancing patient adherence in cardiovascular disease management. The application of NIR spectroscopy for real-time monitoring highlights its broader significance in pharmaceutical manufacturing, where it can serve as a versatile tool for ensuring product quality and optimizing production efficiency in diverse formulation processes. By incorporating NIR-based PAT, manufacturers can not only achieve product-specific improvements but also establish a foundation for continuous manufacturing and automated quality assurance systems, ultimately contributing to a more streamlined and robust production environment. Full article

Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on morphological evaluation alone. This leads to patients requiring numerous embryo transfers and, consequently, a prolonged time interval before live birth. Embryo selection following preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) has been suggested as an intervention to shorten time to pregnancy in women undergoing in vitro fertilisation (IVF). Past studies assessing the clinical efficacy of PGT-A in improving clinical outcomes have been conflicting and the associated clinical pregnancy rates and live birth rates following the transfer of a mosaic embryos have yet to be determined. None of the existing studies solely included women of advanced reproductive age (ARA). The pilot study and proposed RCT will determine if, compared to morphological evaluation alone, the use of PGT-A through NGS is a more clinically effective, safer, and more cost-effective way to provide IVF treatment in women of advanced reproductive age. Method and Analysis: The proposed pilot study will aim to randomise 100 patients within a single-centre study to evaluate recruitment, randomisation, and adherence to study protocol and allocated trail arms by participating patients. The results of the pilot study will enable us to determine the sample size for a larger study to establish the effectiveness of PGT-A in ARA women. Ethics and Dissemination: The study (Integrated Research Application System Number 236067) received approval from the Health Research Authority and Health and Care Research Wales (HCRW) and the East Midlands—Leicester South Research Ethics Committee (20/EM/0290). The results will be made available to patients, the funders, the Reproductive Medicine societies, and other researchers. Trial registration: ClinicalTrials.gov Identifier: NCT05009745, n. Full article

Background/Objectives: Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating. Methods: In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics. Results: The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile. Conclusions: The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations. Full article