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In this study, we aimed to investigate the inhibitory mechanisms of β‐glucuronidase by flavonoids derived from Alhagi graecorum through both experimental and computational approaches. The activity of β‐glucuronidase was assessed using an in vitro enzyme inhibition assay, where myricetin and chrysoeriol were identified as potent inhibitors based on their low IC50 values. Kinetic studies were conducted to determine the inhibition type, revealing that both compounds exhibit noncompetitive inhibition of β‐glucuronidase‐catalyzed hydrolysis of PNPG. Molecular docking was employed to explore the binding affinities of the flavonoids, showing that myricetin formed the highest number of polar interactions with the enzyme. Additionally, molecular dynamics (MD) simulations were performed to evaluate the stability of the enzyme‐inhibitor complexes, demonstrating consistent trajectory behavior for both compounds, with significant energy stabilization. Interaction energy analyses highlighted the dominant role of electrostatic forces in myricetin′s inhibition mechanism, while Van der Waals forces were more prominent for chrysoeriol. The MM/PBSA method was used to calculate the binding free energies, with myricetin and chrysoeriol exhibiting the lowest values. Potential energy landscape analysis further revealed that β‐glucuronidase adopts a more closed conformation when bound to these inhibitors, limiting substrate access. These findings suggest that flavonoids from Alhagi graecorum hold promise for clinical applications, particularly in managing drug‐induced enteropathy. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus complex is a group of rapidly growing non-tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d , d- transpeptidases and l , d- transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Viral infectious diseases are spread worldwide. Search for natural antiviral therapy from natural resources to overcome the serious drawbacks of synthetic chemicals is imperative. The antiviral activity against influenza virus subtype H9N2, Herpes simplex II (HSV II), Adenovirus (AdVs), and Newcastle virus (NDV) was assessed using the cytopathic effect (CPE) inhibition assay. Phytochemical investigation of Eriocephalus africanus var. africanus aerial parts led to the isolation and identification of bioactive compounds including a mixture of aromatic hydrocarbons 1 , 3 β -friedelinol 2 , eicosanol 3 , 1-hexadecanol 4 , β -sitosterol 5 , undecanol 6 , pectolinarigenin 7 , cirsilineol 8 , chrysoeriol 9 , kaempferol 10 , tricin 11 , luteolin 12 , 2,4- dihydroxyacetophenone 13 , ferulic acid 14 , β -sitosterol glucoside 15 , afzelin 16 , hesperidin 17 , kaempferitrin 18 , d-(+)–pinitol 19 and 1,5–dimethyl citrate 20. The antiviral assessment revealed promising activity for the total extract against H9N2, HSV II, NDV, and AdVs with selectivity index (SI) = 12.4, 20.8, 27.4, and 12.9, respectively. The Petroleum ether fraction (PE) had promising anti-H9N2, NDV and the adenovirus with SI = 12.1, 17.0, and 19.1, respectively. Molecular modeling study proved promising activity for β -sitosterol with H9N2 (ΔG = -7.17 Kcal/mol), kaempferitrin with HSV-II (ΔG = -7.64 Kcal/mol), 3 β -friedelinol with AdVs (ΔG = -7.63 kcal/mol), and pectolinarigenin with NDV (ΔG = -7.55 Kcal/mol.). The top 4 candidates showed promising druglikeness and drug-score with no potential toxicity except for pectolinarigenin and kaempferitrin. They showed low to high probability for intestinal absorption, no BBB permeation with zero PAINS alerts and ease for synthetic accessibility. This may establish the promising potential of such compounds for further development into clinical candidates. [Display omitted] • Chromatographic isolation and spectroscopic identification of the bioactive compounds from the aerial parts of Eriocephalus africanus var. africanus cultivated in Egypt. • In silico and in vitro antiviral activity for Eriocephalus africanus total methanol extract as well as other solvent fractions together with the previously isolated essential oil against influenza a virus subtype H9N2, Herpes simplex II, Adeno virus and Newcastle virus. • Estimation of ADME/Tox for isolated compounds. [ABSTRACT FROM AUTHOR]

This study investigates the cytotoxicity of various orthodontic archwires, which are essential in directing tooth movement through biomechanical forces. With advancements in material science, different archwire materials have been developed to balance mechanical performance with aesthetic and biological considerations. The study focuses on evaluating the biocompatibility and mechanical properties of stainless steel, nickel–titanium, and chromium–cobalt archwires, particularly their cytotoxic effects on oral cavity cells. In vitro cell culture experiments with fibroblasts, combined with scanning electron microscopy (SEM) analysis, were conducted to assess cell viability and morphology. The results revealed significant differences in cytotoxicity, with copper wires showing high toxicity and causing extensive cell death, while nickel–titanium and chromium–cobalt wires supported better cell viability and healthier cell morphology. These findings highlight the importance of selecting archwire materials that ensure mechanical efficiency without compromising cellular health, emphasizing the need for ongoing assessment of material biocompatibility in the oral environment. [ABSTRACT FROM AUTHOR]

Loratadine (LOR) is a second-generation antihistamine that exhibits a low and variable oral bioavailability (10–40%) and delayed onset owing to poor solubility and an extensive first-pass effect. Therefore, in light of the clinical need, the main goal of the present study was to develop sublingual fast-dissolving thin films of LOR–citric acid co-amorphous systems (LOR-CAs) with the aim of eliciting a faster onset and improving the bioavailability. We formulated sublingual fast-dissolving thin films of LOR by a film-casting technique using hydrophilic polymers like hydroxypropyl methylcellulose (HPMC E15), polyvinyl pyrrolidone K30 (PVP K30), and hydroxypropyl cellulose EL (HPC-EF) and citric acid as a pH modulator, while glycerin served as a plasticizer. The sublingual fast-dissolving thin films were characterized by FTIR, SEM, DSC, and XRD and evaluated for in vitro dissolution and ex vivo mucoadhesion. The best formulation (F1) developed using HPMC E15 as a polymer, glycerin as a plasticizer, and citric acid as a pH modulator was found to be the optimized formulation as it was smooth, clear, flexible, and displayed good mucoadhesion (11.27 ± 0.418 gm/cm2) and uniform thickness (0.25 ± 0.02 mm). The formulation F1 was found to display a significantly shorter DT (30.30 ± 0.6 s) and rapid release of LOR (92.10 ± 2.3% in 60 min) compared to other formulations (ANOVA, p < 0.001). The results indicated that the prepared sublingual films are likely to elicit a faster therapeutic effect, avoid first-pass metabolism, and improve the bioavailability. [ABSTRACT FROM AUTHOR]

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Encapsulation of bioactive molecules for therapeutic use is gaining great interest in the scientific community. Several encapsulation methodologies have been evaluated, sacrificing, in some cases, either encapsulation efficiency or compound integrity. Our work developed Maillard conjugates (MCs) based on the whey protein (WP)‐Maltodextrin (MD) interaction to encapsulate quercetin by freeze‐drying. The WP:MD ratio used (1:2 or 1:3) yielded the formation of MCs, demonstrated by an increased browning index and changes in the protein secondary structure. Freeze‐drying showed high encapsulation efficiency, reaching 87.65% and 84.72% in treatments loaded with 3.3 mg quercetin/g MCs. Quercetin‐loaded MCs showed spherical‐shape (4–10 μm) and a negative charge, suggesting colloidal stability. Moreover, in vitro tests demonstrated a sustained release of quercetin throughout the oral, gastric, and intestinal phases, highlighting the MCs efficacy as bioactive delivery systems. This work provides useful information to design bioactive compound delivery systems for food and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this research was to develop a fast, reliable, and sensitive method to simultaneously quantify five key components of Huai-hua Powder (HHP) in rat plasma with genistein served as the internal standard. Furthermore, the established method was used to perform a comparative evaluation of the pharmacokinetic properties of HHP in normal rats and rats with ulcerative colitis (UC). Methods: Chromatographic separation was conducted using an ACQUITY HSS T3 column held at a constant temperature of 35°C, with acetonitrile and a 0.1% formic acid solution in water employed as the mobile phases. Multiple-reaction monitoring facilitated MS operation in positive-negative-ion-switching mode. The method's validation demonstrated exceptional linearity (with a correlation coefficient of r ≥ 0.9970), and the validation tests, encompassing precision within and between days, accuracy, recovery, matrix effect, and stability; all met the predefined acceptable criteria. Key findings: The results revealed significant variations in the pharmacokinetic characteristics of the five components between normal and UC rats, suggesting altered drug metabolism rates and extents in the latter group. Conclusions: These findings offer crucial scientific insights into the potential clinical application of HHP, particularly in the context of treating UC. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effect of mirabegron, a β3‐adrenoceptor agonist with widespread clinical use for treating overactive bladder disease, on isolated healthy human ureter strips. Materials and Methods: This was a prospective study employing a series of in vitro organ bath experiments using ureteral tissues of kidney grafts from 10 healthy donors. The ureteral strips were subjected to cumulative mirabegron concentrations (10−9–10−4.5 M). Effects on frequency or amplitude of spontaneous, 10 mM KCl‐ or EFS‐induced contractions were evaluated. Results: Mirabegron decreased the frequency of spontaneous ureteric contraction in a concentration‐dependent manner. Statistically significant decrease in the frequency of spontaneous contraction was observed at 10−8–10−4.5 M. In 10 mM KCl medium, statistically significant change in frequency was observed at 10−9–10−4.5 M. Statistically significant decrease in the amplitudes of spontaneous contraction was observed at 10−7–10−4.5 M. In a 10 mM KCl medium, statistically significant change in amplitudes was observed at 10−8–10−4.5 M. Conclusions: Mirabegron reduced the amplitude and frequency of human ureter activity in in vitro organ bath studies. This effect was achieved in a dose‐dependent manner on isolated tissue strips. Although monotherapy with mirabegron remains uncertain, this study has the potential to elucidate the mechanism underlying the effectiveness of mirabegron, particularly in combination therapy for ureteral stones. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate and compare the efficiency of grapeseed and pineapple extract in removing smear layer from the apical third of root canal, with and without ultrasonic activation. Methods: Eighty single-rooted permanent teeth were divided into two main groups: Group I: conventional syringe irrigation and Group II: ultrasonic activation. Each group was subdivided into two experimental groups, i.e. grapeseed and pineapple extract and one control group, i.e., 17% ethylenediaminetetraacetic acid (EDTA). For each subgroup, instrumentation was done using ProTaper Gold up to size F3 and irrigated with 5 mL of the respective irrigant, followed by a final rinse of 2.5 mL of 5.25% NaOCl. For Group II, the respective irrigant was ultrasonically activated for 1 min, followed by a final rinse of 2.5 mL of 5.25% NaOCl. Smear layer evaluation was done with scanning electron microscope, and data were statistically analyzed. Results: In Group I, both pineapple and grapeseed extracts were more effective than 17% EDTA in removing smear layer from the apical root canal. However, in Group II, 17% EDTA showed highest efficacy in smear layer removal, followed by pineapple and grapeseed extracts (P < 0.05). Conclusion: Natural extracts such as pineapple and grapeseed seeds extracts exhibit potential for smear layer removal in the apical third, without the disadvantage of dentinal erosion from synthetic smear layer removing agents.

The objective of this study was to examine the impact of rice straw brittleness on its efficacy as roughage for ruminants, in comparison to a wild-type variety, utilizing an in vitro study approach. The experimental design was a complete randomized design (CRD). The experimental treatments included various breeds of rice straw (RS), such as the wild-type (WT, T1), the green brittle bred line 8 and line 13 with brittleness level-3 (GBL8-B3, T2 and GBL13-B3, T3), and the purple brittle bred line 8 with brittleness level-5 (PBL8-B5, T4). The findings revealed that the brittleness RS group had higher levels of crude protein and hemicellulose, and lower levels of cellulose compared to the wild-type group. Brittleness RS varieties showed a significantly greater gas production accumulation (p = 0.001) and IVDMD (p = 0.003) compared to the WT group. At 8 h post-incubation, the brittleness RS group showed significantly higher (p = 0.004) total of volatile fatty acids concentration compared to the WT group. After 1 h of post-incubation, GBL8-B3 exhibited the highest (p = 0.032) proportion of propionate and the lowest (0.009) C2:C3 ratio. Additionally, the brittleness RS did not have any effect on the population of ruminal microorganisms. Based on the brittleness of RS, it can be deduced that it has a greater potential as a roughage source when compared to the wild-type variety, consequently enhancing the quality of RS for roughage intake by ruminants. [ABSTRACT FROM AUTHOR]

The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC—over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bisphosphonate commonly used in orthopaedic and metabolic diseases of the musculoskeletal system, including hypercalcemia, postmenopausal osteoporosis, Paget's disease, etc. The aim of this study was to check whether there were any pharmacological interactions between metamizole and risedronate sodium in in vitro studies. Cell viability was assessed using the MTT method, the number of apoptotic cells was assessed using the labelling TUNEL method, and the cell cycle assessment was performed with a flow cytometer and propidium iodide. This was a pilot study, which is why only two cancer cell lines were tested: D-17 of canine osteosarcoma and U-2 OS of human osteosarcoma. Exposure of the canine osteosarcoma cell line to a combination of risedronate sodium (100 µg/mL) and metamizole (50, 5, and 0.5 µg/mL) resulted in the complete abolition of the cytoprotective activity of metamizole. In the human osteosarcoma cell line, the cytotoxic effect of risedronate sodium was entirely eliminated in the presence of 50 µg/mL of metamizole. The cytoprotective and anti-apoptotic effect of metamizole in combination with risedronate sodium in the tested human and canine osteosarcoma cell lines indicates an urgent need for further in vivo studies to confirm or disprove the potential dose-dependent undesirable effect of such a therapy. [ABSTRACT FROM AUTHOR]

Objectives: Chlorhexidine (CHX)‐based products are the most effective chemical agents used in plaque control and oral disinfection. One of their side effects is tooth and restoration staining. For this reason, CHX products with anti‐discolouration systems (ADS) have been developed. The aim of this in vitro study was to compare different CHX‐based products (gel and mouthwash) with or without ADS in composite colour modification. Methods: Two hundred specimens were created, 100 of which were made of packable composite and 100 of flowable composite. After 24 h, colour coordinates (L*, a*, b*, C*, h°) were recorded using a spectrophotometer (T0). Then, all samples were subjected to a CHX/tea staining model and immersed in human saliva for 2 min. Composite specimens were divided in 10 groups (N = 20). Control groups (PC, FC) were soaked in distilled water and test groups (PG, PGads, FG, FGads, PM, PMads, FM and FMads) were immersed in CHX‐based solutions or brushed with CHX gel. Then the cycle was repeated 6 times, and colour differences (ΔEab and ΔE00) were finally calculated. Results: Through flowable composites, FC and FG showed the highest colour differences, respectively ΔEab = 3.48 ± 1.0, ΔE00 = 2.24 ± 0.6 and ΔEab = 2.95 ± 1.3, ΔE00 = 1.53 ± 0.6. In the composite groups instead, PM and PMads showed the highest colour differences, respectively ΔEab = 2.78 ± 1.3, ΔE00 = 1.94 ± 0.8 and ΔEab = 2.71 ± 1.4, ΔE00 = 1.84 ± 0.9. Conclusions: CHX‐containing products are able to cause stains on restorative composite materials. Discolouration is more likely to occur in flowable composites than packable composites, and ADS‐containing products cause fewer pigmentations than CHX products without ADS. Packable composites showed more staining after mouthwash treatment, whereas flowable composites underwent higher discolouration after treatment with gels. [ABSTRACT FROM AUTHOR]

Objectives: Orthodontists are often asked to remove fixed retainers before patients undergo magnetic resonance imaging (MRI). The present in vitro study was designed to analyze the heating and bonding efficacy of stainless steel multibraided fixed retainers after 1.5- and 3-tesla (T) MRI. Materials and methods: A total of 180 human mandibular incisors were used to create 45 specimens of four teeth each, divided into nine groups. Handmade multibraided fixed retainers of three different sizes, defined by the diameter of the initial wire used (0.008″, 0.010″ and 0.012″), were tested. Three groups underwent MRI at 1.5 T, another three groups underwent MRI at 3 T and the last three groups did not undergo MRI. Temperature was assessed before and after MRI. Shear bond strength (SBS) and adhesive remnant index (ARI) were assessed after MRI for all groups. Data were statistically analyzed (p < 0.05). Results: After 1.5 T exposure, no significant temperature increase from T0 to T1 was observed in any of the groups (p > 0.05). Regarding the 3 T groups, a significant difference from T0 to T1 was found for all the groups (p < 0.05). Temperature changes were not clinically relevant, as they were less than 1 °C for all groups except for group 3 (ΔT0–T1: 1.18 ± 0.3 °C) and group 6 (ΔT0–T1: 1.12 ± 0.37 °C). Furthermore, there were no significant differences between the temperature variations associated with different wire diameters (p > 0.05). Conclusions: No significant changes in SBS or ARI were found (p > 0.05). Clinical significance: Since overheating was irrelevant and adhesion values did not change, the tested devices were concluded to be safe for MRI examinations at 1.5 T and 3 T. [ABSTRACT FROM AUTHOR]

Background: Despite the large variety of retainer wires available, no studies could be found comparing the micromechanical properties and surface roughness of different retainer wires. Such characteristics affect the survival of the fixed retainer in terms of both fracture resistance and resistance to debonding from the tooth. Therefore, the aim of the present study was to examine and compare those characteristics in popular retainer wires. Methods: six different popular orthodontic retainer wires were subjected to instrumental indentation based on the Oliver and Pharr method. The geometric surface structure was analysed using a non-contact profilometer. Results: stainless steel wires had a higher hardness and a higher elastic modulus compared to titanium wires and white gold chain. The titanium wire and the white gold chain showed much more roughness than other wires. Conclusions: stainless steel wires are the most resistant, considering both the shape retention capacity and the ability to resist abrasive wear. The titanium wire showed the lowest hardness and, thus, the highest susceptibility to deformation. Bond-a-braid, Retainium and Orthoflex white gold are more resistant to fracture than other steel wires. Titanium wire and chain retainer wires have more roughness, which is a great advantage in terms of mechanical adhesion to composite materials. [ABSTRACT FROM AUTHOR]

Today, diabetes is a common morbidity, and the occurrence of the disease is attributed to various pathophysiological states of the human body, including inflammation and free radical oxidants. Previous types of research also reported the involvement of free radical oxidants in the development of secondary complications of diabetes. The scavenging of free radicals by antioxidants turns out to be a defense mechanism and can also alter disease states. Therefore, the study was designed to evaluate the properties of Bauhinia variegata L. leaves in controlling diabetes, inflammation, and free radicals. The ethanolic leaf extract was prepared and the extract was then fractionated with solvents, which were further used to perform pharmacological screening by in vitro methods. The IC50 values of the chloroform fraction (BVC) of leaf extract were recorded as the lowest among the test materials for all in vitro studies. The IC50 values of BVC in the study of inhibition of a-amylase and a-glucosidase enzymes were 31.08±1.53 and 25.33±1.52 μg/mL, respectively. In the study of inhibition of bovine serum albumin and egg albumin denaturation, BVC showed efficacy with IC50 values of 23.75±1.35 and 28.15±1.32 μg/mL, respectively. The fraction showed free radical scavenging activity in DPPH and nitric oxide assay, with IC50 values of 27.78±1.61 and 34.93±1.49 μg/mL, respectively. In addition, two pure compounds, namely chrysoeriol and β-amyrin palmitate, were isolated from this bioactive fraction. Thus, the results proved all the claimed pharmacological effects of the leaves of Bauhinia variegata L. and also justified the hypothesis of the current study. [ABSTRACT FROM AUTHOR]

Pink pepper is classified into the Californian/Peruvian type (Schinus molle) and the Brazilian type (S. terebinthifolia). According to studies, pink pepper extracts and essential oils have shown anti-inflammatory, antioxidant, genotoxic and antidiabetic properties in in vitro and in vivo studies. The results of bioactivity tests vary depending on the geographical origin of the pepper. In this paper, the cytotoxic, antioxidant and antibacterial effects of the essential oil of the commercial pink pepper fruit from the Tuzla market were investigated. To assess the cytotoxic potential, a tetrazolium salt reduction (MTT) viability assay was performed. The antioxidant potential was examined spectrophotometrically, using DPPH and FRAP methods. Diffusion techniques were used to evaluate the antibacterial activity of the essential oil. Using GC/MS, 24 components of red pepper essential oil were identified, of which α-pinene, α-phellandrene, δ-3-carene and D-limonene dominate. The studied pink pepper essential oil inhibited the cell proliferation in the HeLa cell line, causing a dose-dependent cytotoxic effect (IC50=389.46 µg/mL). The essential oil inhibits DPPH radicals. The reducing ability is relatively weak. For the essential oil, an extremely good ability to inhibit the growth of the bacteria used in this study was confirmed. These results indicate a very high potential of essential oil of pink pepper fruit as an inhibitor of pathogenic organisms. [ABSTRACT FROM AUTHOR]

Background Bacterial contamination of implants has been linked to biofilm formation and subsequent infection, capsular contracture, and breast implant–associated anaplastic large cell lymphoma. Reducing contamination during implant insertion should therefore reduce biofilm formation disease sequelae. Objectives The aim of this study was to compare levels of contamination between preventative techniques. Methods A model to simulate the passage of implants through a skin incision was designed that utilized a sterile textured polyvinyl plastic sheet contaminated with Staphylococcus epidermidis. In the first stage of the polyvinyl contamination model, implants were subject to infection-mitigation techniques and passed through the incision, then placed onto horse blood agar plates and incubated for 24 hours. In the second stage of the study the same contamination was applied to human abdominal wall specimens. A 5 cm incision was made through skin and fat, then implants were passed through and levels of contamination were measured as described. Results Smooth implants grew a mean of 95 colony-forming units (CFUs; approximately 1 CFU/cm2) and textured implants grew 86 CFUs (also approximately 1 CFU/cm2). CFU counts were analyzed by the Mann-Whitney U -test which showed no significant difference between implant types (P <.05); independent-sample t -tests showed a significant difference. The dependent-variable techniques were then compared as groups by one-way analysis of variance, which also showed a significant reduction compared with the control group (P <.01). Conclusions This in vitro study has shown the effectiveness of antiseptic rinse and skin/implant barrier techniques for reducing bacterial contamination of breast implants at the time of insertion. [ABSTRACT FROM AUTHOR]

ABSTRACT Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

Sesuvium portulacastrum, a coastal medicinal plant with traditional uses has shown promising biological activities including anti-inflammatory, antioxidant and antimicrobial properties. However, the mechanisms of action active ingredients of this plant have not been studied. Aim of the current study is to investigate the anticancer activity of Sesuvium portulacastrum using in vitro and in silico analysis. The in vitro assays included NO radical scavenging activity, total phenolic and flavonoid content determination. The data were analysed by one-way-ANOVA and p

Background: The current standard of radiotherapy for inoperable locally advanced NSCLCs with single fraction doses of 2.0 Gy, results in poor outcomes. Several fractionation schedules have been explored that developed over the past decades to increasingly more hypofractionated treatments. Moderate hypofractionated radiotherapy, as an alternative treatment, has gained clinical importance due to shorter duration and higher patient convenience. However, clinical trials show controversial results, adding to the need for pre-clinical radiobiological studies of this schedule. Methods: We examined in comparative analysis the efficiency of moderate hypofractionation and normofractionation in four different NSCLC cell lines and fibroblasts using several molecular-biological approaches. Cells were daily irradiated with 24x2.75 Gy (moderate hypofractionation) or with 30x2 Gy (normofractionation), imitating the clinical situation. Proliferation and growth rate via direct counting of cell numbers, MTT assay and measurements of DNAsynthesizing cells (EdU assay), DNA repair efficiency via immunocytochemical staining of residual gH2AX/53BP1 foci and cell surviving via clonogenic assay (CSA) were experimentally evaluated. Results: Overall, the four tumor cell lines and fibroblasts showed different sensitivity to both radiation regimes, indicating cell specificity of the effect. The absolute cell numbers and the CSA revealed significant differences between schedules (P < 0.0001 for all employed cell lines and both assays) with a stronger effect of moderate hypofractionation. Conclusion: Our results provide evidence for the similar effectiveness and toxicity of both regimes, with some favorable evidence towards a moderate hypofractionation. This indicates that increasing the dose per fraction may improve patient survival and therapy outcomes. [ABSTRACT FROM AUTHOR]

The gut–brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the underlying molecular processes, has emerged in recent decades. Probiotics have been shown in several trials to help reduce anxiety and depressive symptoms. Because of this, probiotic combinations have been tested in in vitro models to see whether they might modulate the gut and alleviate depression and anxiety. Therefore, we sought to determine whether a novel formulation might affect the pathways controlling anxiety and depression states and alter gut barrier activities in a 3D model without having harmful side effects. Our findings indicate that B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL, and L. paracasei TJB8 10 mg/mL may influence the intestinal barrier and enhance the synthesis of short-chain fatty acids. Additionally, the probiotics studied did not cause neuronal damage and, in combination, exert a protective effect against the condition of anxiety and depression triggered by L-Glutamate. All these findings show that probiotics can affect gut function to alter the pathways underlying anxiety and depression. [ABSTRACT FROM AUTHOR]

For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.3 mm. During cyclic testing, a gradual decrease in height could be detected due to viscoelastic effects and fluid loss. No gel extrusion could be observed for all specimens during the entire test procedure. A macroscopic inspection after dissections showed an accumulation of the solidified gel in the center of the nucleus. The results demonstrate that the injection of in situ solidifying gels through the intact annulus allows for the stable maintenance of the injected gel at the target location, with high potential for use as a suitable scaffold to anchor therapeutically applied cells for disc regeneration within the treated nucleus pulposus. [ABSTRACT FROM AUTHOR]

Many plant diseases are caused by phytopathogenic bacteria which greatly determine the quality of plant production. The biological control of plant pathogenic bacteria is an alternative method to the application of chemicals, which may be accomplished through the destruction of existing inoculums, exclusion from the host, or the suppression or displacement of the pathogen after infection. It offers an environmentally friendly approach to the management of plant disease and can be incorporated with cultural and physical control and limited chemical usage for an effective and integrated disease-management system. Biological control includes the use of beneficial microorganisms, such as specialized fungi and bacteria, to attack and control plant pathogens and the diseases they cause. Biological control is an innovative, cost effective and eco-friendly approach for control of many plant diseases. Bacteria of the genus Bacillus has showed antimicrobial activity against plant pathogenic microorganisms. Bacillus spp. are natural inhabitants of the phyllosphere and rhizosphere. These bacteria are involved in the control of plant diseases through a variety of mechanisms of action, such as competition, systemic resistance induction and antibiotic production. The mechanism of antibiosis has been shown to be one of the most important. Bacillus spp. have the advantage of being already adapted to the environment where they can be applied as biological control. They have the characteristics of having high thermal tolerance, showing rapid growth in liquid culture, and readily form resistant spores. It is considered safe biological agents and their potential as biocontrol agents is considered to be high. This research is based on the isolation and screening of biocontrol activities of soil Bacillus sp. against several phytopathogens in in vitro study. Since tested isolate has showed the production of antimicrobials against the growth of selected phytopathogens, in further work, all of this trial need to be supported by evaluation of antimicrobial activity in in vivo. [ABSTRACT FROM AUTHOR]

Objectives: To compare the accuracy of immediate implant placement of cylindrical implants (CI) and tapered implants (TI) of different lengths using a robotic dental implant system. Materials and Methods: CI and TI of three lengths (8, 10, and 12 mm) each were digitally planned and placed in a three‐dimensional printed extraction socket model under robotic guidance. There were six groups with three samples in each group, resulting in a total of 18 samples. Implant angular deviation, platform point deviation (total, lateral, depth), and implant apical point deviation (total, lateral, depth) were recorded and compared between the different groups. Results: The angular deviations for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 1.32° ± 0.19°, 1.03° ± 0.56°, 1.31° ± 0.38°, 1.27° ± 0.64°, 1.10° ± 0.43° and 1.05° ± 0.45°, respectively. The total deviations of platform and apical points for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 0.79 ± 0.18 mm, 0.77 ± 0.33 mm; 0.64 ± 0.21 mm, 0.55 ± 0.17 mm; 0.64 ± 0.37 mm, 0.65 ± 0.34 mm; 0.68 ± 0.26 mm, 0.71 ± 0.20 mm; 0.70 ± 0.12 mm, 0.66 ± 0.23 mm; and 0.71 ± 0.15 mm, 0.77 ± 0.29 mm, respectively, and had no significant differences. Conclusions: Within the limitation of this study, acceptable accuracy can be achieved for both TI and CI using robotic systems. Our study demonstrated that the implant shape and length did not affect the accuracy of immediate implant placement under robotic guidance in vitro. However, further trials are required to confirm their efficacy in clinical practice. [ABSTRACT FROM AUTHOR]

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds. [ABSTRACT FROM AUTHOR]

Xenon, an inert gas commonly used in medicine, has been considered as a potential option for prolonged preservation of donor packed red blood cells (pRBCs) under hypoxic conditions. This study aimed to investigate how xenon affects erythrocyte parameters under prolonged storage. In vitro model experiments were performed using two methods to create hypoxic conditions. In the first method, xenon was introduced into bags of pRBCs which were then stored for 42 days, while in the second method, xenon was added to samples in glass tubes. The results of our experiment showed that the presence of xenon resulted in notable alterations in erythrocyte morphology, similar to those observed under standard storage conditions. For pRBC bags, hemolysis during storage with xenon exceeded the acceptable limit by a factor of six, whereas the closed-glass-tube experiment showed minimal hemolysis in samples exposed to xenon. Notably, the production of deoxyhemoglobin was specific to xenon exposure in both cell suspension and hemolysate. However, this study did not provide evidence for the purported protective properties of xenon. [ABSTRACT FROM AUTHOR]

Background: Periodontal dressings play a crucial role in post-operative management of periodontal surgeries by protecting surgical sites and promoting wound healing. Biocompatibility evaluation is essential to ensure the safety and effectiveness of these materials. This study aims to assess the biocompatibility of periodontal dressings through an in vitro approach. Materials and Methods: In this in vitro study, three commercially available periodontal dressings were evaluated for their biocompatibility. The Dressings were Dressing A: Coe-Pak™ Dressing B: Barricaid® and Dressing C: PeriAcryl®. Human gingival fibroblast cells were cultured and exposed to extracts of the dressings using the MTT assay to assess cell viability. Additionally, cell morphology and attachment were observed under a microscope. The experiment was conducted in triplicate for each dressing. Results: The MTT assay revealed that Dressing A exhibited the highest cell viability with an absorbance value of 0.8 ± 0.1, followed by Dressing B with a value of 0.6 ± 0.2 and Dressing C with a value of 0.5 ± 0.1. Microscopic analysis showed normal cell morphology and attachment in cells exposed to Dressing A and Dressing B extracts, while cells exposed to Dressing C exhibited slight detachment and irregular morphology. Conclusion: Our findings suggest that Dressing A and Dressing B demonstrate favorable biocompatibility profiles, as evidenced by higher cell viability and normal cell morphology.

Background: Achieving a reliable seal in root canal obturation is essential for the success of endodontic treatment. Despite the availability of multiple techniques, the comparative sealing abilities of these methods remain a topic of investigation, particularly in permanent molars. Materials and Methods: This in vitro study involved 60 extracted permanent molars, divided randomly into three groups: Group A (lateral compaction), Group B (thermoplasticized gutta-percha), and Group C (single cone). After instrumentation and obturation, the sealing ability was assessed using a dye penetration method. Arbitrary values were assigned to quantify the extent of dye penetration. Results: The mean dye penetration values were as follows: Group B (thermoplasticized gutta-percha) had the lowest penetration (2.1 ± 0.3 mm), followed by Group A (lateral compaction) (3.5 ± 0.4 mm), and Group C (single cone) exhibited the highest penetration (5.2 ± 0.6 mm). Conclusion: In this study, thermoplasticized gutta-percha demonstrated superior sealing ability compared to lateral compaction and single cone techniques in permanent molars. These findings underscore the importance of selecting an effective obturation technique to ensure optimal seal integrity in root canal therapy.

Background: Orthodontic appliances can influence the oral environment, including salivary pH levels, which play a crucial role in maintaining oral health. Understanding how different orthodontic appliances affect salivary pH levels can help in improving treatment outcomes and minimizing potential side effects. Materials and Methods: In this in vitro study, we evaluated the effects of various orthodontic appliances on salivary pH levels using a simulated oral environment. Four different types of orthodontic appliances were tested: traditional metal braces, ceramic braces, lingual braces, and clear aligners. Saliva samples were collected and subjected to pH measurements using a standardized method. The pH measurements were recorded at three different time intervals: immediately after appliance placement, after 24 hours, and after 48 hours. Results: The initial pH values varied among the different orthodontic appliances: metal braces (pH 7.2), ceramic braces (pH 7.4), lingual braces (pH 7.1), and clear aligners (pH 7.5). After 24 hours, there was a decrease in pH levels for all groups: metal braces (pH 6.8), ceramic braces (pH 7.0), lingual braces (pH 6.7), and clear aligners (pH 7.2). After 48 hours, the pH levels continued to decrease: metal braces (pH 6.5), ceramic braces (pH 6.8), lingual braces (pH 6.4), and clear aligners (pH 6.9). Conclusion: Our findings suggest that different orthodontic appliances have varying effects on salivary pH levels. Metal braces and lingual braces tend to cause a more pronounced decrease in salivary pH compared to ceramic braces and clear aligners. Monitoring salivary pH levels during orthodontic treatment may be beneficial in identifying potential risks to oral health and implementing appropriate interventions.

Background: Dental implant surfaces play a crucial role in determining the success of osseointegration and long-term stability. Understanding the cellular response to various implant surfaces is essential for optimizing implant design and clinical outcomes. Materials and Methods: In this in vitro study, we investigated the cellular response to different dental implant surfaces. Titanium implants with three distinct surface treatments (polished, acid-etched, and sandblasted) were prepared. Human osteoblast-like cells were cultured on these surfaces, and cellular behaviors including adhesion, proliferation, and morphology were evaluated using standard assays and imaging techniques. Results: Our results revealed significant differences in cellular responses among the different implant surfaces. Cells exhibited higher adhesion and proliferation rates on the acid-etched and sandblasted surfaces compared to the polished surface. Furthermore, cells displayed a more spread-out morphology with well-defined filopodia and lamellipodia on the acid-etched and sandblasted surfaces, indicating enhanced cellular interaction and spreading. Conclusion: The cellular response to dental implant surfaces varies depending on surface characteristics. Acid-etched and sandblasted surfaces promote better cellular adhesion, proliferation, and spreading compared to polished surfaces. These findings underscore the importance of surface modifications in enhancing osseointegration and ultimately improving the success rates of dental implant procedures.

Background: Severe Early Childhood Caries (S-ECC) is a prevalent oral health issue among young children, often associated with specific caries-associated bacteria. This in vitro study investigates the impact of diet on the growth and activity of caries-associated bacteria in S-ECC. Materials and Methods: Plaque samples of Streptococcus mutans and Lactobacillus species were procured from laboratory. The samples were exposed to different dietary conditions, including high-sugar, high-carbohydrate, and control diets. The growth kinetics of caries-associated bacteria, including S. mutans and Lactobacillus species, were monitored using quantitative polymerase chain reaction (qPCR) and colony-forming unit (CFU) assays. Results: Under high-sugar conditions, the growth of S. mutans increased by 50% compared to the control group, as evidenced by qPCR analysis. Lactobacillus species also exhibited a significant increase in CFU counts in response to high-carbohydrate diets, showing a 40% rise compared to controls. Conclusion: This in vitro study highlights the influence of diet on the proliferation of caries-associated bacteria in severe early childhood caries. High-sugar and high-carbohydrate diets contribute to the growth and activity of S. mutans and Lactobacillus species, exacerbating the progression of dental caries in affected children.

Background: Dry eye syndrome (DES) is a prevalent ocular condition characterized by insufficient tear production or excessive tear evaporation, leading to discomfort and visual disturbances. Omega-3 fatty acids have been proposed as a potential therapeutic intervention for DES due to their anti-inflammatory and lipid modulation properties. Materials and Methods: Cultured human corneal epithelial cells were exposed to various concentrations of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for 72 h. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while inflammatory cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8)) and lipid profile (measured by lipid staining) were evaluated using enzyme-linked immunosorbent assay. Untreated cells served as controls for comparison. Results: Omega-3 fatty acid supplementation demonstrated a dose-dependent increase in cell viability compared to untreated cells. At optimal concentrations, EPA and DHA significantly enhanced cell viability by 30% and 35%, respectively (P < 0.05). Moreover, omega-3 fatty acid supplementation led to a significant reduction in inflammatory cytokine levels, with a 50% decrease in IL-6 and IL-8 secretion compared to untreated cells (P < 0.01). Additionally, lipid staining revealed improved lipid profile and organization in corneal epithelial cells following omega-3 fatty acid supplementation, indicative of enhanced tear film stability. Conclusion: In vitro findings suggest that omega-3 fatty acid supplementation exerts beneficial effects on cellular markers associated with DES.

Background: Pterygium is a common ocular surface disorder characterized by the growth of fibrovascular tissue onto the cornea, leading to discomfort and visual impairment. Various surgical techniques, including conjunctival autografting, amniotic membrane transplantation, and bare sclera excision, are employed in the management of pterygium. Materials and Methods: Cultured human conjunctival epithelial cells were subjected to simulated pterygium conditions, mimicking the fibrovascular proliferation observed in vivo. Subsequently, different surgical techniques, including conjunctival autografting, amniotic membrane transplantation, and bare sclera excision, were simulated in vitro. Cell viability, proliferation, migration, and inflammatory cytokine expression were assessed using various assays, including MTT assay, scratch assay, and enzyme-linked immunosorbent assay (ELISA). Untreated cells served as controls for comparison. Results: Conjunctival autografting demonstrated superior outcomes in terms of cell viability and proliferation compared to amniotic membrane transplantation and bare sclera excision. Autografted cells exhibited a significantly higher percentage of viable cells and enhanced proliferative capacity compared to cells subjected to other surgical techniques (P < 0.05). Additionally, conjunctival autografting promoted faster cell migration into the defect area, resulting in more rapid wound closure compared to other techniques. Furthermore, reduced expression of inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), was observed in cells treated with conjunctival autografts compared to other groups. Conclusion: In vitro findings suggest that conjunctival autografting may offer superior outcomes in the management of pterygium compared to amniotic membrane transplantation and bare sclera excision.

Background: The selection between Zirconia crowns and metal crowns for anterior teeth restorations is pivotal in prosthodontics due to their distinct properties. However, a comprehensive investigation into their effectiveness in anterior tooth restorations is warranted. Materials and Methods: This in vitro study aimed to compare the effectiveness of Zirconia crowns and metal crowns in anterior teeth restorations. A total of thirty extracted human maxillary central incisors were prepared to receive crowns and randomly allocated into two groups: group A, zirconia crowns; and group B, metal crowns. The crowns were fabricated following standardized protocols and cemented onto the prepared teeth. Various tests, including fracture resistance, marginal adaptation, and color-matching assessment, were conducted on the samples. Results: The mean fracture resistance of Zirconia crowns (Group A) was determined to be 320 N (SD ± 25), whereas it was 280 N (SD ± 30) for metal crowns (Group B). Marginal adaptation assessment revealed a mean gap width of 50 microns (SD ± 10) for Zirconia crowns and 70 microns (SD ± 15) for metal crowns. Evaluation of color matching showed a higher percentage of acceptable matches for Zirconia crowns compared to metal crowns. Conclusion: Zirconia crowns exhibited superior fracture resistance, marginal adaptation, and color matching in comparison to metal crowns for anterior teeth restorations. These findings advocate for Zirconia crowns as a more effective choice for restoring anterior teeth, offering both strength and esthetic appeal.

Background: Endodontic procedures require precise manipulation and visualization to achieve optimal treatment outcomes. Magnification and enhanced visualization tools, such as dental loupes and dental operating microscopes (DOMs), have been introduced to enhance precision in endodontic practice. Materials and Methods: Extracted human teeth with single-rooted canals were divided into two groups: a control group without magnification and an experimental group with magnification and enhanced visualization. Endodontic procedures, including access cavity preparation, cleaning, shaping, and obturation, were performed on both groups. The experimental group utilized either dental loupes or a DOM for enhanced visualization. Treatment outcomes were assessed based on predefined criteria, including the quality of access cavity preparation, canal cleanliness, shaping, and obturation. Scores were assigned to each criterion to quantify treatment precision. Results: The use of magnification and enhanced visualization significantly improved precision in endodontic procedures compared to the control group. Access cavity preparation in the experimental group resulted in more conservative tooth structure removal and improved visualization of canal orifices. Canal cleanliness, shaping, and obturation were markedly superior in the experimental group, with higher scores indicating better precision. The experimental group also exhibited a reduced incidence of procedural errors and complications compared to the control group. Conclusion: Magnification and enhanced visualization tools, such as dental loupes and DOMs, enhance precision in endodontic procedures.

Background: Gutta-percha is commonly used in endodontic therapy for obturating root canals after cleaning and shaping procedures. Warm and cold gutta-percha techniques are two common methods employed for obturation, each with its own advantages and limitations. Materials and Methods: Twenty extracted human teeth with single-rooted canals were selected and divided into two groups: warm gutta-percha obturation and cold gutta-percha obturation. In the warm gutta-percha group, gutta-percha was heated to a predetermined temperature using a warm gutta-percha heating device and injected into the root canal using a heated carrier. In the cold gutta-percha group, gutta-percha was applied directly to the root canal without prior heating. Root canal obturation quality was assessed using radiographic imaging to evaluate the presence of voids, completeness of obturation, and adaptation to the canal walls. Micro-computed tomography (micro-CT) analysis was also performed to quantify the volume of obturating material and assess the three-dimensional distribution of gutta-percha within the root canal space. Results: Both warm and cold gutta-percha techniques demonstrated effective obturation of root canals, with comparable outcomes in terms of void formation, completeness of obturation, and adaptation to canal walls. However, micro-CT analysis revealed differences in the volume and distribution of gutta-percha within the root canal space. Warm gutta-percha obturation exhibited more uniform distribution of gutta-percha material and higher volumetric filling compared to cold gutta-percha obturation. Additionally, the warm gutta-percha technique demonstrated superior flowability and adaptation to irregularities within the root canal system. Conclusion: In this in vitro study, warm gutta-percha obturation demonstrated advantages over cold gutta-percha obturation in terms of volumetric filling, distribution within the root canal space, and adaptation to canal irregularities.

Cancer is the second most fatal disease among women. In recent years, utilizing strategies based on carbon quantum dots (CQDs) as targeted drug delivery systems has had a significant impact on advancing and improving cancer treatment. This study is focused on the development of a nanocarrier, based on CQDs, for improving the therapeutic efficiency of mitoxantrone (MTX). Hence, the N-doped CQDs were synthesized by a hydrothermal method. Following its purification, MTX was loaded to the CQD, resulting in an increase in the size from 36.78 ± 0.9 nm to 157.8 ± 12.18 nm, with an ideal drug entrapment efficiency of 97 %. Drug release investigation showed a pH-dependent improvement, from 8 % at pH 7.4 to 11 % at pH 5.2 after 48 h. Based on the Methylthiazolyldiphenyl-tetrazolium bromide (MTT) results after 5 h of treatment on MCF-7 breast cancer cells, the N-doped CQD showed no significant effect on the cancer cells, whereas a half maximal Inhibitory Concentration (IC50) was achieved with the N-doped CQD-MTX complex at a concentration between 0.5 to 0.8 μM. Therefore, the newly developed drug delivery complex was capable of providing a rather identical influence on MCF-7 cells, as the free MTX, however, improving the pharmacokinetic of the drug by its controlled and on-target drug release, due to an alteration in distribution and absorption parameters.

Abstract Background Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing. Methods Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay. Results Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib. Conclusion Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing.

Polyphenols exert a wide range of biological effects, including immunomodulatory action. Studying the effects of flavonoids on phagocytic activity of specialized phagocytic cells seems to be a rather promising direction for their further usage as pharmacological (therapeutic) agents. Quercetin and luteolin are the most commonly studied flavonoid substances with pleiotropic action. In-depth study and understanding of immunotropic mechanisms (e.g., regulation of phagocytosis) is a prerequisite for adequate pharmacotherapy in infectious conditions, nonspecific inflammatory diseases, autoimmune and oncological disorders. The aim of our work is to study the effect of flavonoids upon phagocytic activity of professional phagocytes (neutrophils) using an in vitro test system. The biological material (venous blood) from 30 practically healthy people (adults n = 15, children n = 15) was used in the present work. The study was carried out in accordance with established international regulations. 0.5 mg/L of Luteolin (basic substance content ≥ 98%) and Quercetin (basic substance content ≥ 95%) were added to experimental samples and incubated for 20 min at 37 °С. The percentage of phagocytosis, phagocytic number (mean number of formalin-treated sheep erythrocytes engulfed per one neutrophil) was determined in control and experimental samples using light microscopy. The unidirectional nature of phagocytosis inhibition by quercetin and luteolin was noted in the test experiments. A statistically significant (p < 0.05) decrease in the phagocytosis intensity by 10% was shown in experimental blood samples obtained from adult patients compared with control values. When quercetin and luteolin were added to blood samples obtained from children, a statistically significant (p < 0.05) decrease in phagocytosis by 30% was noted against control values. At the same time, the mean percentage of phagocytosis and phagocytic number in blood samples after the addition of flavonoids were found to be in the range of reference values, thus suggesting adequacy and physiological suppression of excessive activities of innate immunity compartments by quercetin and luteolin. At this concentration, the flavonoids were found to exert a more pronounced suppressive effect on phagocytic activity in children. Modeling of immune response using the phagocytosis indices assayed in experimental in vitro models with neutrophils from practically healthy adults and children enables us to expand the knowledge of mechanisms underlying the immunotropic effects of flavonoids (quercetin and luteolin), in order to correct immunopathological conditions.

This study was designed to estimate the effect of garlic extract on H. pylori isolated from poultry meat at Dhamar Governorate, Yemen. In the laboratory, the isolation of H. pylori was done under aseptic conditions using modified Campy-blood agar and Belohorizonte agar. Purification isolates were done on the same agar media-biochemical examinations employed for the identification comprised essential biochemical tests. In vitro studies, show that H.pylori was survived at 2% of garlic extract, whereas at 4% and 6%, it was observed that the inhibition zone 10mm and 20mm respectively. In an experimental study, the count number of H. pylori was reduced with 2% and 4% of garlic extract, while at 6% no growth occurred. We concluded that treating chicken meat with garlic extract reduces the number of H.pylori cells, and garlic extract plays an important role in food preservation. Due to the significance of this study, we recommend further research and studies on H. pylori in different governorates of Yemen, particularly on the prevalence of H. pylori in various types of food, mainly food of animal origin, and study the impact of some medicinal plants such as garlic.

Additional therapeutics are required to minimize the toxicity of aflatoxin B1 (AFB1) in animals due to the drawbacks of mycotoxin binders. The cytochrome P450 enzyme system is necessary for the metabolic activation of AFB1 before it produces the cytotoxic AFB1-exo-8, 9-epoxide (AFBO). It is already proven that enrofloxacin (ENR) has been shown to substantially decrease the activity of the cytochrome P450 enzymes. To understand how ENR affects AFB1-induced cytotoxicity, it is important to highlight this context. In this present study, molecular docking was performed between ENR with CYP3A4 protein, apoptotic proteins (Bax, caspase 3, caspase 8, fas L, MAPK1), and catalase. To assess the effect of ENR on AFB1-induced cytotoxicity by MTT assay and trypan blue dye exclusion techniques, the mammalian simulative Vero cell lines were used in different treatment groups as AFB1 alone, ENR alone, AFB1+ENR, and AFB1+silymarin (known cell protective agent). This was done to further evaluate the in silico analysis. ENR interacted more positively with all of the proteins (CYP3A4, Bax, catalase, caspase 3, caspase 8, MAPK1, and fas L), according to the findings of molecular docking studies. On the other hand, cytotoxicity caused by AFB1 is successfully prevented by ENR at a dose of 25 µg/mL. The results of the present study suggest that ENR primarily protects against cytotoxicity induced by AFB1 in Vero cells as the evidence of in silico studies revealed that ENR may protect AFB1-induced cytotoxicity by interacting with the CYP3A4 enzyme which is primarily required for activation AFB1.

Background: Zingiber officinale rhizome is widely cultivated in the central region of Sudan (Gezira) and data on the biological properties of this variety grown in Sudan’s climate are scarce. This study aims to comprehensively analyze the antibacterial, antioxidant, phytochemical, and GC-MS properties of Zingiber officinale (ginger rhizome) to explore its potential applications. Methods and Results: The in vitro antibacterial assessment of the aqueous extract of Sudanese ginger revealed moderate activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia, as determined by the disc diffusion method. The inhibition zones ranged from 12.87 ± 0.11 mm to 14.5 ± 0.12 mm at 30 µg/disc. The minimum inhibitory concentration ranged from 6.25 to 25 µg/mL, while the MBC ranged from 25 to 50 µg/mL. The MBC/MIC exhibited a bactericidal effect against all tested bacteria. Phytochemical screening revealed the presence of various chemical constituents, such as saponins, flavonoids, glycosides, alkaloids, steroids, terpenoids, and the absence of tannins in Sudanese ginger rhizome. Furthermore, GC-MS analysis of ginger rhizome identified 22 chemical compounds with retention times ranging from 7.564 to 17.023 min. The identification of 22 chemical compounds through GC-MS analysis further underscores the prospect of harnessing ginger rhizome for the development of novel medications. Computational analyses showed that ginger compounds bind the Protein Data Bank (PDB) codes 1JIJ and 2QZW with high binding affinities, reaching −9.5 kcal/mol. Ginger compounds also established promising molecular interactions with some key residues, satisfactorily explaining the in vitro results and supporting the pharmacokinetic and experimental findings. Conclusions: This study lays the groundwork for future research and pharmaceutical exploration aimed at harnessing the beneficial properties of ginger rhizome for medicinal and therapeutic purposes, particularly its antimicrobial potential.

Background: Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing. Methods: Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay. Results: Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib. Conclusion: Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing. [ABSTRACT FROM AUTHOR]

Saccharomyces cerevisiae var. boulardii has been used as a probiotic yeast in the medical and food industries. Colon cancers have been known as the third most common cancer type worldwide. Nowadays, cell-free extract and metabolites of probiotics have been employed for the treatment or prevention of different cancer diseases. This study investigates the anticancer properties of S. boulardii metabolites against human colon carcinoma. We evaluated cytotoxicity, apoptosis induction, and suppression of survivin, IL-8, and NFƙB gene expression effects of SBM against caco-2 cells after 24 and 48 h. IC50 concentrations of SBM were measured at 815 and 1411 µg/mL for 24 and 48 h treatments, respectively. The total proportion of apoptotic caco-2 cells treated with SBM after 24 and 48 h were calculated at 62.23 and 88.7%, respectively. Also, relative expression of survivin, IL-8, and NFƙB genes were significantly suppressed in caco-2 cells treated with SBM after 24 and 48 h. In conclusion, we found that SBM induced apoptosis, inhibited the growth rate, and suppressed the expression of the survivin, IL-8, and NFƙB genes in human colorectal cancer cells and it can be considered as a perspective supplement or drug for the treatment or prevention of colon cancer in humans. [ABSTRACT FROM AUTHOR]

PURPOSE. The present experiment aimed to evaluate the placement accuracy of fully guided implant surgery using a mucosa-supported surgical guide when the protocol of osteotomy and installation was modified (MP) compared to when the protocol was sequentially and conventionally carried out (CP). MATERIALS AND METHODS. For 24 mandibular dentiform models, 12 dentists (6 experts and 6 beginners) performed fully guided implant placements two times at the right first and second molar sites using a mucosa-supported surgical guide, once by the CP (CP group) and at the other time by the MP (MP group). The presurgical and postsurgical stereolithographic images were superimposed, and the deviations between the virtually planned and actually placed implant positions and the procedure time were compared statistically (P < .05). RESULTS. The accuracies were similar in the CP and MP groups. In the CP group, the mean platform and apex deviations at the second molar site for the beginners were +0.75 mm and +1.14 mm, respectively, which were significantly larger than those for the experts (P < .05). In the MP group, only the mean vertical deviation at the second molar site for the beginners (+0.53 mm) was significantly larger than that for the experts (P < .05). The procedure time was significantly longer for the MP group (+94.0 sec) than for the CP group (P < .05). CONCLUSION. In fully guided implant surgery using a mucosa-supported guide, the MP may improve the placement accuracy when compared to the CP, especially at sites farther from the most-posterior natural tooth. [ABSTRACT FROM AUTHOR]

Background Endodontic treatment aims to thoroughly clean and shape the root canal system while preserving the structural integrity of the tooth. The choice of endodontic file system can significantly impact the outcomes of this procedure. This in vitro study compares debris extrusion, remaining dentin thickness, and fracture resistance in endodontically treated teeth using rotary and reciprocating endodontic file systems. Materials and Methods Forty extracted human mandibular premolars were selected and randomly divided into two groups (n=20 each): Group A was prepared using a rotary file system, and Group B was prepared using a reciprocating file system. Debris extrusion was quantified using the Myers and Montgomery method, and remaining dentin thickness was measured at the coronal, middle, and apical thirds of each root. Fracture resistance was evaluated using a universal testing machine. The data were analyzed using appropriate statistical tests. Results The mean debris extrusion in Group A was 0.25 mg, while in Group B, it was 0.18 mg. The remaining dentin thickness in Group A was 1.24 mm, 1.15 mm, and 1.06 mm at the coronal, middle, and apical thirds, respectively, while in Group B, it was 1.30 mm, 1.22 mm, and 1.14 mm. The mean fracture resistance in Group A was 888 N, and in Group B, it was 920 N. Conclusion The reciprocating endodontic file system exhibited less debris extrusion, slightly greater remaining dentin thickness, and slightly higher fracture resistance compared to the rotary file system, although these differences were not statistically significant. Both file systems can be considered safe and effective for endodontic treatment, with the choice depending on clinician preference and specific clinical scenarios. [ABSTRACT FROM AUTHOR]