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Lubna Al Asoom,1 Maha A Alassaf,2 Najd S AlSulaiman,3 Dhuha N Boumarah,4 Aldana M Almubireek,2 Gaeda K Alkaltham,2 Hussain A Alhawaj,5 Taleb Alkhamis,5 Nazish Rafique,1 Ahmed Alsunni,1 Rabia Latif,1 Seham Alsaif,1 Dana Almohazey,6 Sayed AbdulAzeez,7 J Francis Borgio7 1Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2King Fahd hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Department of Internal Medicine, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Surgery, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 5Animal House, Environmental Health Department, Institute for Research and Medical Consultation, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 6Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 7Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Lubna Al Asoom, Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O Box 2004, Dammam, 31541, Saudi Arabia, Tel +966505846344, Email lasoom@iau.edu.saBackground: Obesity is a global pandemic that is associated with high morbidity and mortality. Natural herbs are commonly used for weight reduction and appetite suppression. Therefore, we aim to investigate the role and mechanism of Nigella sativa (NS) and ginger on weight reduction and appetite regulation.Methods: This experimental study was performed at Imam Abdulrahman Bin Faisal University. Twenty-five female rats were distributed into 5 groups: NS (oral 1000mg/kg), Ginger (500 mg/kg), NS-ginger (both interventions), a positive control (intraperitoneal 50 μg/kg Liraglutide), and a negative control. Each intervention was given for 9 weeks. Food intake and body weight were assessed weekly. Serum lipid profile and peptides involved in appetite control (cholecystokinin (CCK), glucagon-like peptide 1(GLP-1), gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, and orexin) were assayed at the end of the experiment.Results: None of the interventions showed a statistically significant difference regarding food consumption or weight gain (p > 0.05). However, the three interventions significantly reduced total cholesterol (TC), NS and NS-ginger significantly increased HDL, NS increased ghrelin and ginger increased orexin.Conclusion: The present dose and duration of NS, ginger, or in combination did not demonstrate a significant change in body weight or food consumption in comparison to the negative or positive controls. However, NS or ginger has improved the lipid profile by reducing TC and increasing HDL. In addition, NS or ginger can influence some of the peptides involved in appetite regulation such as the increase in ghrelin induced by NS and the reduction of orexin induced by ginger. We believe that these latter effects are novel and might indicate a promising effect of these natural products on appetite regulation.Keywords: Nigella sativa, ginger, body weight, appetite, Liraglutide

This study evaluated the reliability of sealer penetration measurement methods used with confocal laser scanning microscopy in correlation with the percentage of residual root filling and examined the effect of residual root-filling material on dentine penetrability after retreatment. Extracted teeth were randomly divided into different groups according to the obturation sealer used (n = 6); BioRoot RCS; MTA Fillapex; Bio-C and AH Plus. Root-filling material was removed before the secondary chemo-mechanical preparation and obturation using fluorescein labelled AH Plus. Multiple micro-computed tomography scans were obtained followed by confocal laser scanning microscopy to measure the penetration of the labelled sealer into the dentinal tubules using four different methods. Measuring sealer penetration into radicular dentine using the penetration percentage method was found to be the most reliable. Dentine penetrability during retreatment did not seem to be affected by the type of residual root-filling material., (© 2024 Australian Society of Endodontology Inc.)

This study aimed to evaluate the fracture resistance of root and sealer penetration after obturation using an epoxy resin sealer AH plus (AH+) and two different bioactive endodontic sealers, i.e., Totalfill BC Hiflow (TF BC), and experimental injectable bioactive glass (Exp.BG). A thermo-sensitive injectable sealer was prepared by using a non-ionic triblock copolymer and bioactive glass. The root canals of human extracted teeth were obturated with the respective sealers. The fracture resistance was analyzed at different time intervals, i.e., days 7, 30, and 90. The morphological and elemental analyses of the fractured roots were conducted with a scanning electron microscopy and a electron dispersive spectroscopy. Sealer penetration depth and the percentage of penetrated sealers into the dentinal tubules were assessed with the confocal laser scanning microscope. Statistical analysis was performed using a one-way ANOVA post hoc Tukey's test. The mean fracture force in AH+ was significantly higher on day 30 (664.08 ± 138.8 N) compared to day 7 (476.07 ± 173.2 N) and day 90 (493.38 ± 120.18 N). There was no statistically significant difference between the TF BC and Exp.BG at different time intervals. The maximum penetration was observed in the middle region compared to coronal and apical for the Exp.BG, followed by the TF BC and AH+ groups; however, a nonsignificant difference in penetration was found over time. It is concluded that the TF BC group showed overall better fracture resistance than AH+ at day 90. Exp.BG showed comparable sealer penetration to those of TF BC and better than those of AH+.

The emergence of multidrug-resistant fungi Candida auris is a worldwide health crisis connected with high rates of mortality. There is a critical need to find novel and unique antifungal compounds for treating infections of multidrug-resistant fungi such as C. auris . This study aimed to illustrate that biosynthetic gene clusters in native bacterial isolates are able to produce antifungal compounds against the multidrug-resistant fungus C. auris. It was successfully achieved using large-scale antifungal activity screening, cytotoxicity analysis, and whole genome sequencing integrated with genome mining-guided analysis and liquid chromatography-mass spectrometry (LC/MS). A list of possible gene candidates was initially identified with genome mining methods to predict secondary metabolite gene clusters of antifungal-compound-producing bacteria. Then, gene clusters present in the antifungal-compound-producing bacteria were identified and aligned with the reference genome using comparative genomic approaches. Bacillus halotolerans AQ11M9 was identified through large-scale antifungal activity screening as a natural compound-producer against multidrug-resistant C. auris , while it was nontoxic to normal human skin fibroblast cells (confirmed using a cell viability assay). The genome (4,197,347 bp) of B. halotolerans AQ11M9 with 2931 predicted genes was first mined for detecting and characterizing biosynthetic gene clusters, which revealed 10 candidate regions with antifungal activity. Clusters of AQ11M9 encoded non-ribosomal peptide synthase (NRPS) (bacilysin, bacillibactin, paenibactin, surfactin, plipastin, and fengycin) and polyketide (macrobrevin). The presence of gene clusters with anti- C. auris activity, and surfactin identified through LC/MS, from AQ11M9 suggests the potential of utilizing it as a source for a novel and powerful anti- C. auris compound.

Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris . In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti- C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase-dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti- auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris , and significant ( p -value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti- C . auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection.

A chemo-drug such as cisplatin is effective for cancer treatment but remains non-specific, is susceptible to drug resistance, and induces several side effects on organ systems. Zeolitic imidazolate framework-8, a type of MOF, has gained attention, including as a drug delivery method for targeted cancer therapeutics. In this study, ZIF-8/Silica nanocomposite was synthesized using a one-pot hydrothermal technique using the Stober technique. We studied the effect of phyto-synthesized GPt and chemo-drug cisplatin CPt on ZIF-8/Silica for targeted efficacy of cancer therapy. The texture, morphology, and chemical environment of Pt on ZIF-8/Silica were analyzed using different characterization techniques such as XRD, FT-IR, BET, diffuse reflectance spectroscopy, SEM-EDX, TEM, zeta potential, and TGA analysis. The isothermal behavior of CPt and GPt adsorption was investigated using isotherm models like Langmuir, Freundlich, and Temkin isotherm. The adsorption kinetics indicating the adsorption efficiency of GPt and CPt are influenced by the concentration of Pt complex and the adsorption sites of ZIF-8/Silica. A high entrapment efficiency and loading capacity of GPt (86% and 4.3%) and CPt (91% and 4.5%) were evident on ZIF-8/Silica. The nanocomposite showed a pH-sensitive Pt release using a dialysis membrane technique. For instance, a high release of GPt (93%) was observed under pH = 6.6 in 72 h, while the release reduced to 50% at pH 7.4 in 72 h. The anti-cancer activity of nanoformulations was studied in vitro using MCF7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) cells. The findings demonstrated that GPt is as effective as CPt; the EC50 value for MCF7 cells treated with ZIF-8/Silica/Cp/PEG was 94.86 µg/mL, whereas for ZIF-8/Silica/GPt/PEG it was 60.19 µg/mL.

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe 2 O 4 /GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe 2 O 4 /silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn 2+ species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt 4+ species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe 2 O 4 /silica/cisplatin and MnFe 2 O 4 /GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death.

Colorectal cancer is one of the most aggressive types of cancer with about two million new cases and one million deaths in 2020. The side effects of the available chemotherapies and the possibility of developing resistance against treatment highlight the importance of developing new therapeutic options. The development in the field of nanotechnology have introduced the application of nanoparticles (NPs) as a promising approach in the diagnosis and treatments of colorectal cancer and other types of cancer. Gold nanoparticles (AuNPs) are currently one of the most studied materials as they possess unique tunable properties allowing them to play a role in colorectal cancer bioimaging, diagnosis, and therapy. The high surface-to-volume ratio of AuNPs mediates their utilization in drug delivery as well as functionalization to provide specific targeting. Moreover, depending on their physical properties (size, shape), AuNPs can be modified to fit the intended application. However, there are contradictory results around the pharmacokinetics of AuNPs including their biodistribution, clearance, and toxicity. This variation of opinions is most likely due to the development of different AuNPs that vary in shape, size, and surface chemistry, in addition to the conditions under which each research was carried out. The conflicting data represent a challenge in the clinical use of AuNPs suggesting the need to understand the toxicity, fate, and long-term exposure of AuNPs in vivo. Thus, there is an unmet need for the establishment of a publicly available data base for extensive analysis. In this review, we discuss the recent advances in AuNP applications in the treatment and diagnosis of colorectal cancer, mechanisms of action, and clinical challenges., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objectives : Sickle cell anemia (SCA) is a hereditary monogenic disease due to a single β-globin gene mutation that codes for the production of sickle hemoglobin. Its phenotype is modulated by fetal hemoglobin (HbF), a product of γ-globin genes. Exploring the molecules that regulate γ-globin genes at both transcriptional and translational levels, including microRNA (miRNA), might help identify alternative therapeutic targets. Materials and Methods : Using next-generation sequencing we identified pre-miRNAs and mature miRNA expression signatures associated with different HbF levels in patients homozygous for the sickle hemoglobin gene. The involvement of identified miRNAs in potential SCD-related pathways was investigated with the DIANA TOOL and miRWalk 2.0 database. Results : miR-184 were most highly upregulated in reticulocytes. miR-3609 and miR-483-5p were most highly downregulated in sickle cell anemia with high HbF. miR-370-3p that regulates LIN28A, and miR-451a which is effective in modulating α- and β- globin levels were also significantly upregulated. miRNA targeted gene pathway interaction identified BCL7A, BCL2L1, LIN28A, KLF6, GATA6, solute carrier family genes and ZNF genes associated with erythropoiesis, cell cycle regulation, glycosphingolipid biosynthesis, cAMP, cGMP-PKG, mTOR, MAPK and PI3K-AKT signaling pathways and cancer pathways. Conclusions : miRNA signatures and their target genes identified novel miRNAs that could regulate fetal hemoglobin production and might be exploited therapeutically.