Predictors of procedural errors in class II resin composite restorations using bitewing radiographs.

Objective: To identify the potential factors that induce procedural errors during posterior proximal resin composite restorations placed by dental students. Materials and Methods: This retrospective study evaluated 803 bitewing radiographs of posterior proximal resin composite restorations placed by dental students at Imam Abdulrahman bin Faisal University. Atypical radiographic signs of failure were screened, and different patient-, operator-, and clinical-related factors were recorded. Chi-square test was used to examine the relationship between procedural errors and recorded factors. Stepwise adjusted logistic regression model was performed to identify predictors of procedural errors. Results: The most observed errors were internal gaps at the bonding interface and internal voids. Molars had 0.39 the risk of internal voids (odds ratio [OR] = 0.39; confidence interval [CI] = 0.25-0.60; P = <0.0001), 0.41 the risk of sharp angle (OR = 0.41; CI = 0.24-0.68; P = <0.001), and 0.57 the risk of open contact (OR = 0.57; CI = 0.34-0.97; P = 0.04) compared to premolars. Those who were >40 years of age had 1.79 the risk of overhang compared to younger patients (OR = 1.79; CI = 1.04-3.11; P = <0.04). First molars and premolars had 0.64 the risk of overhang compared to second molars and premolars (OR = 0.64; CI = 0.41-1.00; P = 0.04). Junior students had 1.97 the risk of internal gap compared to their senior counterparts (OR = 1.97; CI = 1.20-3.21; P = 0.008). Mesial restorations had 0.38 the risk of external gap compared to mesio-occluso-distal (MOD) restorations (OR = 0.38; CI = 0.19-0.78; P = 0.003). Restorations with a margin coronal to the cemento-enamel junction (CEJ) had 0.44 the risk of external gap compared to those restorations with a margin apical to the CEJ (OR = 0.44; CI = 0.29-0.66; P = <0.0001). Conclusion: Our findings suggested a higher incidence of procedural errors in restoring premolars and MOD cavity preparations. Therefore, it is crucial to enhance the comprehensiveness of laboratory training and expose students to diverse clinical scenarios and various techniques.

Lichen Planus of the Eyelids: Case Report of a Rare Presentation of a Common Dermatosis.

Lichen planus (LP) is a common T-cell-mediated autoimmune skin disease, and its exact etiology is unknown. Typically, it affects the trunk, flexural surfaces, and the mucosa.We report a rare finding of LP involving both eyelids in a 67-year-old female. A 67-year-old Saudi female with a medical history of diabetes mellitus, hypothyroidism and rheumatoid arthritis presented with a three-month history of pruritic skin eruptions in both eyelids. She had no associated musculoskeletal symptoms or fatigue and no medical or family history of atopy. The patient had violaceous, thin, scaly plaques confined to both eyelids. Oral mucosa, genitalia, scalp, and nails were not affected. Histopathology from the right lower eyelid confirmed the diagnosis of LP. Hepatitis C virus serology was negative. Patient was examined by ophthalmology to rule out conjunctival involvement of LP. She had dry eyes only. She was initially managed by topical tacrolimus 0.1% ointment and didn't tolerate it due to severe reaction. She tolerated mometasone propionate 0.1% cream, which relieved the itch and partially improved the lesions. Although rare, LP of the eyelids must be considered among differential diagnoses of eyelid dermatitis. It can be confined, or it may concomitantly involve other parts of the body. LP of the eyelid may also extend to the conjunctiva, so it's important to screen patients by ophthalmology to rule out possible ocular involvement. This is the first case report of a Saudi patient with LP confined to the eyelid. The management of LP involving the eyelids is challenging. Treatment options include topical steroids, tacrolimus ointment, phototherapy and oral retinoids (etretinate).

Ultrasound-Facilitated, Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (APE) poses a significant risk to patient health, with treatment options varying in efficacy and safety. Ultrasound-facilitated catheter-directed thrombolysis (USCDT) has emerged as a potential alternative to conventional catheter-directed thrombolysis (CDT) for patients with intermediate to high-risk APE. This study aimed to compare the efficacy and safety of USCDT versus conventional CDT in patients with intermediate to high-risk APE. METHODS: This observational retrospective study was conducted at the Armed Forces Hospital, Al-Hada, Taif, the Kingdom of Saudi Arabia (KSA), on 135 patients diagnosed with APE and treated with either USCDT or CDT (58 underwent CDT, while 77 underwent USCDT). The primary efficacy outcome was the change in the right ventricle to the left ventricle (RV/LV) diameter ratio. Secondary outcomes included changes in pulmonary artery systolic pressure and the Miller angiographic obstruction index score. Safety outcomes focused on major bleeding events. RESULTS: Both USCDT and CDT significantly reduced RV/LV diameter ratio (from 1.35 ± 0.14 to 1.05 ± 0.17, P < 0.001) and systolic pulmonary artery pressure (SPAP) (from 55 ± 7 mmHg to 38 ± 7 mmHg, P < 0.001) at 48- and 12-hours post-procedure, respectively, with no significant differences between treatments. However, USCDT was associated with a significantly lower rate of major bleeding events compared to CDT (0% vs. 3.4%, P = 0.008). Multivariate logistic regression analysis revealed that USCDT was associated with a 71.9% risk reduction of bleeding (OR = 0.281, 95% CI = 0.126 - 0.627, P = 0.002). CONCLUSIONS: USCDT is a safe and effective alternative to CDT for the treatment of intermediate to high-risk APE, as it significantly reduces the risk of major bleeding.

Circumferential Esophageal Reconstruction Using a Tissue-engineered Decellularized Tunica Vaginalis Graft in a Rabbit Model.

BACKGROUND: Pediatric surgeons have faced esophageal reconstruction challenges for decades owing to a variety of congenital and acquired conditions. This work aimed to introduce a reproducible and efficient approach for creating tissue-engineered esophageal tissue using bone marrow mesenchymal stem cells (BMSCs) cultured in preconditioned mediums seeded on a sheep decellularized tunica vaginalis (DTV) scaffold for partial reconstruction of a rabbit's esophagus. METHODS: DTV was performed using SDS and Triton X-100 solutions. The decellularized grafts were employed alone (DTV group) or after recellularization with BMSCs cultured for 10 days in preconditioned mediums (RTV group) for reconstructing a 3 cm segmental defect in the cervical esophagus of rabbits (n = 20) after the decellularization process was confirmed. Rabbits were observed for one month, after which they were euthanized, and the reconstructed esophagi were harvested for histological analysis. RESULTS: Six rabbits in the DTV group and eight rabbits in the RTV group survived until the end of the one-month study period. Despite histological examination demonstrating that both grafts completely repaired the esophageal defect, the RTV graft demonstrated a histological structure similar to that of the normal esophagus. The reconstructed esophagi in the RTV group revealed the arrangement of the different layers of the esophageal wall with the formation of newly formed blood vessels and Schwann-like cells. CONCLUSION: DTV xenograft is a novel scaffold that promotes cell adhesion and differentiation and might be effectively utilized for regenerating esophageal tissue, paving the way for future clinical trials in pediatric patients.

Primary arthrodesis for diabetic ankle fractures using a modified retrograde femoral intramedullary locking nail combined with lateral plating, surgical technique, and early results of a pilot study.

PURPOSE: We aimed to report the early results of performing acute ankle arthrodesis using a modified retrograde femoral intramedullary locking IMN concomitant with plating at the same setting for managing diabetic patients' acute ankle fractures. METHODS: We prospectively included patients who presented acutely with ankle fractures, where hemoglobin A1C (HbA1C) on admission was > 7%, and the Adelaide Fracture in the Diabetic Ankle (AFDA) algorithm score was 5 or above. All patients were treated by acute ankle arthrodesis using a modified retrograde femoral IMN combined with lateral plating. Functional assessment was reported according to a modified American Orthopaedic Foot and Ankle Society ankle hindfoot scale (AOFAS), and complications were documented. RESULTS: Six patients had an average age of 55.7 years (37-65). The average HbA1C on admission was 7.9 (7.3-9), and the average AFDA score was 7.3 (6-8). The average operative time was 79.2 min (70-90). All patients, except for one, achieved union at the arthrodesis site after an average of 10.3 weeks (8-14). After an average last follow-up of 9 months (6-12), the average modified AOFAS was 73.2 (82 to 62); four patients had an excellent score and one good. Complications developed in two, one deep infection after 2 weeks treated by metal removal and Ilizarov, and the other patient developed a stress fracture at the tibial end of the nail, which was treated by open reduction and internal fixation using a plate and screws. CONCLUSION: Using a modified femoral IMN combined with lateral plating is a promising technique to achieve ankle arthrodesis in diabetic patients with acute ankle fractures with acceptable outcomes; however, further studies with larger numbers are needed. LEVEL OF EVIDENCE: IV.

Vertebral Fracture Associated With Extracorporeal Shock Wave Lithotripsy: A Case Report.

Extracorporeal shock wave lithotripsy (ESWL) is considered a safe, reliable, and non-invasive modality for kidney stone management. However, there are well-established complications related to ESWL documented in the literature in the form of renal and extrarenal complications. Skeletal complications related to ESWL are rarely recorded; as far as we know, there is only one documented case report of an ESWL-related burst vertebral fracture seen in an osteoporotic patient, diagnosed as granulomatous spondylitis. Here, we present a novel case of a transverse process fracture of the third lumbar vertebra related to ESWL in a young patient otherwise free from any medical illness.

Sequential graph convolutional network and DeepRNN based hybrid framework for epileptic seizure detection from EEG signal.

Automated epileptic seizure detection from ectroencephalogram (EEG) signals has attracted significant attention in the recent health informatics field. The serious brain condition known as epilepsy, which is characterized by recurrent seizures, is typically described as a sudden change in behavior caused by a momentary shift in the excessive electrical discharges in a group of brain cells, and EEG signal is primarily used in most cases to identify seizure to revitalize the close loop brain. The development of various deep learning (DL) algorithms for epileptic seizure diagnosis has been driven by the EEG's non-invasiveness and capacity to provide repetitive patterns of seizure-related electrophysiological information. Existing DL models, especially in clinical contexts where irregular and unordered structures of physiological recordings make it difficult to think of them as a matrix; this has been a key disadvantage to producing a consistent and appropriate diagnosis outcome due to EEG's low amplitude and nonstationary nature. Graph neural networks have drawn significant improvement by exploiting implicit information that is present in a brain anatomical system, whereas inter-acting nodes are connected by edges whose weights can be determined by either temporal associations or anatomical connections. Considering all these aspects, a novel hybrid framework is proposed for epileptic seizure detection by combined with a sequential graph convolutional network (SGCN) and deep recurrent neural network (DeepRNN). Here, DepRNN is developed by fusing a gated recurrent unit (GRU) with a traditional RNN; its key benefit is that it solves the vanishing gradient problem and achieve this hybrid framework greater sophistication. The line length feature, auto-covariance, auto-correlation, and periodogram are applied as a feature from the raw EEG signal and then grouped the resulting matrix into time-frequency domain as inputs for the SGCN to use for seizure classification. This model extracts both spatial and temporal information, resulting in improved accuracy, precision, and recall for seizure detection. Extensive experiments conducted on the CHB-MIT and TUH datasets showed that the SGCN-DeepRNN model outperforms other deep learning models for seizure detection, achieving an accuracy of 99.007%, with high sensitivity and specificity.

Does the marketing age impact growth performance, carcass traits, economic feasibility and hemato-biochemical properties of genetically-modified quails?

The meat of the quail is one of the most delicious types, as it is rich in minerals and vitamins, especially vitamin K, which is useful in treating nervous diseases. In the present investigation, based on their live body weight, 270 genetically-enhanced white quail chicks of mixed sex were randomly assigned to 3 groups, each with 90 chicks. The first group's birds were slaughtered at 28 d of age. The birds in the second group were slaughtered at 31 d, and the birds in the third group were slaughtered at 34 d. Results showed no significant difference between the various groups in the overall mortality rate index at the end of each fattening stage (P > 0.05). There were substantial variations (P ≤ 0.05) in the average live weight index between the first and both groups at each group's marketing age. With increasing marketing age, body weight increases. Quail chicks raised for 34 d received the lowest EPEF (28.90 points), followed by those raised for 31 d and 28 d, which received 33.37 and 37.32 points, respectively. The economic feasibility of the 3 groups, no significant differences in the profit index were observed at the age of 28 d. Compared to the marketing age of the other 2 groups, it was noted that the profit index decreased as the birds advanced in age. Delaying marketing to 31 d leads to a decrease in profit by 5.7%, and delaying marketing to 34 d reduces the profit index to 26.36% compared to marketing at 28 d. For blood hematology parameters, a significant increase in the studied indicators with the age of the birds was observed through the study of blood indicators. Still, it did not reach the significance level. It could be concluded that 28 d is the ideal marketing age for the enhanced white quails, as it yielded the highest economic return and the best performance.

An ingenious technique based on the usage of fluorone-based dye; pyrosin B in prucalopride assay in different matrices through an "on-off" dye native fluorescence probe.

Prucalopride (PCD), is a modern medication approved by the United States in 2018 to alleviate constipation caused by motility issues. PCD demonstrates a strong affinity and selectivity toward the 5-HT4 receptor. The study here introduces a feasible, direct, non-extractive, and affordable pathway for PCD analytical tracking. The fluorimetric study is based on the on-off effect on the emission amplitude of fluorone-based dye (pyrosin B). In a one-pot experiment, the complex between PCD and pyrosin B is formed instantly in an acidic medium. Correlation between decreased pyrosin B emission and PCD concentrations provides a linear calibration plot from 50 to 900 ng/mL. PCD-dye complex system affecting variables were meticulously tuned. The values of the estimated limit of quantitation and limit of detection for the current methodology were 47.5 and 15.7 ng/mL, respectively. Conformity of the strategy validity was achieved by a comprehensive study of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use criteria. The method was convincingly applied for PCD assay in tablets and content uniformity investigation. Furthermore, PCD tracking in the spiked biological fluid was applied. Finally, the method uses distilled water as dispersing medium which rise accommodation with the green chemistry principle.

Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were downregulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.

Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.

Salvimulticanol from Salvia multicaulis suppresses LPS-induced inflammation in RAW264.7 macrophages: in vitro and in silico studies.

Sustained inflammatory responses can badly affect several vital organs and lead to chronic inflammation-related disorders, such as atherosclerosis, pneumonia, rheumatoid arthritis, obesity, diabetes, Alzheimer's disease, and cancers. Salvia multicaulis is one of the widely distributed plants that contains several biologically active phytochemicals and diterpenoids with anti-inflammatory effects. Therefore, finding alternative and safer natural plant-extracted compounds with good curative anti-inflammatory efficiencies is an urgent need for the clinical treatment of inflammation-related diseases. In the current study, S. multicaulis Vahl was used to extract and isolate two compounds identified as salvimulticanol and candesalvone B methyl ester to examine their effects against inflammation in murine macrophage RAW264.7 cells that were induced by lipopolysaccharide (LPS). Accordingly, after culturing RAW264.7 cells and induction of inflammation by LPS (100 ng/ml), cells were exposed to different concentrations (9, 18, 37.5, 75, and 150 µM) of each compound. Then, Griess assay for detection of nitric oxide (NO) levels and western blotting for the determination of inducible nitric oxide synthase (iNOS) expression were performed. Molecular docking and molecular dynamics (MD) simulation studies were employed to investigate the anti-inflammatory mechanism. Our obtained results validated that the level of NO was significantly decreased in the macrophage cell suspensions as a response to salvimulticanol treatment in a dose-dependent manner (IC50: 25.1 ± 1.2 µM) as compared to the methyl ester of candesalvone B which exerted a weaker inhibition (IC50: 69.2 ± 3.0 µM). This decline in NO percentage was comparable with a down-regulation of iNOS expression by western blotting. Salvimulticanol strongly interacted with both the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKß) to disrupt their inflammatory activation due to the significant hydrogen bonds and effective interactions with amino acid residues present in the target proteins' active sites. S.multicaulis is a rich natural source of the aromatic abietane diterpenoid, salvimulticanol, which exerted a strong anti-inflammatory effect through targeting iNOS and diminishing NO production in LPS-induced RAW264.7 cells in a mechanism that is dependent on the inhibition of TLR4-MD-2 and IKKß as activators of the classical NF-κB-mediated inflammatory pathway.

Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo.

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.

Assessment of modified chitosan composite in acidic reservoirs through pilot and field-scale simulation studies.

Chemical flooding through biopolymers acquires higher attention, especially in acidic reservoirs. This research focuses on the application of biopolymers in chemical flooding for enhanced oil recovery in acidic reservoirs, with a particular emphasis on modified chitosan. The modification process involved combining chitosan with vinyl/silane monomers via emulsion polymerization, followed by an assessment of its rheological behavior under simulated reservoir conditions, including salinity, temperature, pressure, and medium pH. Laboratory-scale flooding experiments were carried out using both the original and modified chitosan at conditions of 2200 psi, 135,000 ppm salinity, and 196° temperature. The study evaluated the impact of pressure on the rheological properties of both chitosan forms, finding that the modified composite was better suited to acidic environments, showing enhanced resistance to pressure effects with a significant increase in viscosity and an 11% improvement in oil recovery over the 5% achieved with the unmodified chitosan. Advanced modeling and simulation techniques, particularly using the tNavigator Simulator on the Bahariya formations in the Western Desert, were employed to further understand the polymer solution dynamics in reservoir contexts and to predict key petroleum engineering metrics. The simulation results underscored the effectiveness of the chitosan composite in increasing oil recovery rates, with the composite outperforming both its native counterpart and traditional water flooding, achieving a recovery factor of 48%, compared to 39% and 37% for native chitosan and water flooding, thereby demonstrating the potential benefits of chitosan composites in enhancing oil recovery operations.

Electronic and Molecular Adsorption Properties of Pt-Doped BC6N: An Ab-Initio Investigation.

In the last two decades, significant efforts have been particularly invested in two-dimensional (2D) hexagonal boron carbon nitride h-BxCyNz because of its unique physical and chemical characteristics. The presence of the carbon atoms lowers the large gap of its cousin structure, boron nitride (BN), making it more suitable for various applications. Here, we use density functional theory to study the structural, electronic, and magnetic properties of Pt-doped BC6N (Pt-BC6N, as well as its adsorption potential of small molecular gases (NO, NO2, CO2, NH3). We consider all distinct locations of the Pt atom in the supercell (B, N, and two C sites). Different adsorption locations are also considered for the pristine and Pt-doped systems. The formation energies of all Pt-doped structures are close to those of the pristine system, reflecting their stability. The pristine BC6N is semiconducting, so doping with Pt at the B and N sites gives a diluted magnetic semiconductor while doping at the C1 and C2 sites results in a smaller gap semiconductor. We find that all doped structures exhibit direct band gaps. The studied molecules are very weakly physisorbed on the pristine structure. Pt doping leads to much stronger interactions, where NO, NO2, and NH3 chemisorb on the doped systems, and CO2 physiorb, illustrating the doped systems' potential for gas purification applications. We also find that the adsorption changes the electronic and magnetic properties of the doped systems, inviting their consideration for spintronics and gas sensing.

Antifungal and antibacterial investigation of quinary Zr Al Fe Co Ni layered double hydroxide and its Al Fe Co Ni quaternary and Fe Co Ni tertiary roots.

Layered double hydroxides (LDH) are promising 2D nanomaterials being investigated for several engineering and biomedical applications. In this work, quinary Zr Al Fe Co Ni LDH and its Al Fe Co Ni LDH quaternary and Fe Co Ni LDH tertiary roots were prepared and characterized. All samples showed an aggregated, layered morphology with zero surface charge and approximately 300 nm of hydrodynamic size. BET surface area of Al Fe Co Ni LDH showed a remarkable value of 143.25 m2 g-1 as opposed to 26.2 m2 g-1 and 45.4 m2 g-1 for Fe Co Ni LDH and Zr Al Fe Co Ni LDH, respectively. The antimicrobial activity of the prepared samples was assessed against the many pathogenic bacteria; Bacillus (B.) subtilis, Escherichia (E.) coli, Haemophilus (H.) influenza, Listeria (L.) monocytogenes, Staphylococcus (S.) aureus, and Streptococcus (St.) pneumonia, and six fungal species. Furthermore, anti-biofilm activity, growth curve assay, and effect of UV illumination were examined against various pathogenic microbes. Zr Al Fe Co Ni displayed remarkable antibacterial activity, as indicated by the lowest values of the minimum inhibitory concentrations (MIC) of 4-166.7 µg mL-1. Results for fungal strains varied in terms of their susceptibilities for the different samples tested. Zn Al Fe Co Ni was able to inhibit the biofilm formation of S. aureus (96.09%), E. coli (98.32%), and Candida (C.) albicans (95.93%). This study shown that certain LDH categories, particularly Zr Al Fe Co Ni, may be promising antibacterial agents against variety of pathogenic microorganisms that cause serious infections.

Anticancer diterpenes of African natural products: Mechanistic pathways and preclinical developments.

BACKGROUND: The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural products have compelling cytotoxic activities that warrant further exploration for the drug market, particularly in cancer therapy, where mortality rates remain elevated worldwide. PURPOSE: To demonstrate the potential of African natural products on the global stage for cancer therapy development and provide an in-depth analysis of the current literature on the activity of cancer cytotoxic diterpenes from African natural sources (to our knowledge, the first of its kind); not only to reveal the most promising candidates for clinical development, but to demonstrate the importance of preserving the threatened ecosystems of Africa. METHODS: A comprehensive search by means of the PRISMA strategy was conducted using electronic databases, namely Web of Science, PubMed, Google Scholar and ScienceDirect. The search terms employed were 'diterpene & mechanism & cancer' and 'diterpene & clinical & cancer'. The selection process involved assessing titles in English, Portuguese and Spanish, adhering to predefined eligibility criteria. The timeframe for inclusion spanned from 2010 to 2023, resulting in 218 relevant papers. Chemical structures were visualized using ChemDraw 21.0, PubChem was utilized to search for CID numbers. RESULTS: Despite being one of the richest biodiverse zones in the world, African natural products are proportionally underreported compared to Asian countries or otherwise. The diterpenes andrographolide (Andrographis paniculata), forskolin (Coleus forskohlii), ent-kauranes from Isodon spp., euphosorophane A (Euphorbia sororia), cafestol & kahweol (Coffea spp.), macrocylic jolkinol D derivatives (Euphorbia piscatoria) and cyathane erinacine A (Hericium erinaceus) illustrated the most encouraging data for further cancer therapy exploration and development. CONCLUSIONS: Diterpenes from African natural products have the potential to be economically significant active pharmaceutical and medicinal ingredients, specifically focussed on anticancer therapeutics.

MCT4 knockdown by tumor microenvironment-responsive nanoparticles remodels the cytokine profile and eradicates aggressive breast cancer cells.

Breast cancer is a wide-spread threat to the women's health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by ∼90 % at low siRNA concentrations, with a subsequent ∼80 % cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90 % and ∼64 % reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.

Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice.

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase.

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.