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Biology subjects

Ibrahim, Y.

Publications and source records attributed to Ibrahim, Y..

6 recordsLinked to original sources

A Pro-Regenerative Petroleum Jelly-Based, Copper-Doped Bioactive Glass Ointment for Impaired Wound Healing in Metabolic Syndrome

Chronic wound healing is often impaired in conditions such as metabolic syndrome, requiring effective therapeutic interventions to promote tissue regeneration and repair. In this study, we evaluated the wound healing potential of petroleum jelly (P Jelly)-based bioactive glass ointments (PBGCu) with varying copper concentrations (0, 1, and 3 wt%) in both in vitro and in vivo models of wound healing. PBGCu formulations demonstrated high biocompatibility with human dermal fibroblasts (HDF) and human umbilical vein endothelial cells (HUVEC). Additionally, PBGCu ointments exhibited strong antibacterial activity against Staphylococcus aureus, suggesting their utility for the care of chronic wounds. In both metabolic syndrome mouse and pig models, PBGCu3-treated wounds showed significantly faster wound closure, enhanced epithelial regeneration, and increased dermal thickness compared to saline and P Jelly controls. Histological analysis also revealed 50% increased vascularization (p < 0.0001) and a 90% reduction in scar formation (p < 0.0001) in PBGCu3-treated wounds. These findings show that PBGCu formulations, especially at 3 wt% copper concentration, significantly improve wound healing by promoting epithelial regeneration, dermal tissue formation, and vascularization, while also offering antibacterial protection. The sustained Cu2+ ions release from PBGCu ointments provides long-term support for tissue regeneration, positioning this ointment composition as a promising therapeutic tool for chronic wound management. Future studies will focus on elucidating the underlying mechanisms and evaluating the therapeutic efficacy of PBGCu formulations in infected wounds. HighlightsO_LIDeveloped a Petroleum Jelly-based copper-doped bioactive glass ointment (PBGCu) enabling sustained and controlled Cu{superscript 2} ion release. C_LIO_LIPBGCu significantly accelerated wound closure and improved epithelial and dermal tissue regeneration. C_LIO_LIPBGCu enhanced hair follicle regeneration and tissue remodeling in full-thickness wounds. C_LIO_LIValidated therapeutic efficacy in both mouse and pig models that support translational relevance. C_LIO_LIOffers a simple, low-cost, and clinically adaptable topical formulation for metabolic syndrome-related wound complications. C_LI

bioengineering↗

Development of a Platform for High-Resolution Ion Mobility Separations Coupled with Messenger Tagging Infrared Spectroscopy for High-Precision Structural Characterizations

The ability to uniquely identify a compound requires highly precise and orthogonal measurements. Here we describe a newly developed analytical platform that uniquely integrates high resolution ion mobility and cryogenic vibrational ion spectros-copy for high-precision structural characterizations. This platform allows for the temporal separation of isomeric/isobaric ions and provides a highly sensitive description of the ions adopted geometry in the gas phase. The combination of these orthogonal structural measurements yields precise descriptors that can be used to resolve between and confidently identify highly similar ions. The unique benefit of our instrument, which integrates a structures for lossless ion manipulations ion mobility (SLIM IM) device with messenger tagging infrared spectroscopy, include increased resolution and the ability to record the IR spectra of all ions simultaneously. The SLIM IM device, with its 13m separation path length, allows for multipass experiments to be performed for increased resolution as needed. It is integrated with an Agilent qTOF MS where the collision cell was retrofitted with a cryogenically (30 K) held TW SLIM device. The cryo-SLIM is operated in a novel manner that allows ions to be streamed through the device and collisionally cooled to a temperature where they can form non-covalently bound N2 complexes that are maintained as they exit the device and are detected by the TOF mass analyzer. The instrument can be operated in two modes: IMS+IR where the IR spectra for mobility-selected ions can be recorded and IR-only mode where the IR spectra for all mass-resolved ions can be recorded. In IR-only mode, IR spectra (400 cm-1 spectral range) can be recorded in as short as 2 seconds for high throughput measurements. This work details the construction of the instrument, modes of operation, and provides initial benchmarking of CCS and IR measurements to demonstrate the utility of this instrument for targeted and untargeted approaches.

bioinformatics↗

Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics

Hippocampal neurogenesis plays instrumental roles in learning and memory. However, the mechanisms underlying neurogenesis are not fully understood. Here we show that the expression of Caveolin-1 (Cav-1), the principal component of caveolae, peaks in neural progenitor cells (NPCs) during neurogenesis. Using NestinCreERT2;Cav-1fl/fl male mice, and CRISPR-sham (Cav-1 Ctrl) and CRISPR/Cas9-edited (Cav-1 KO) human induced-pluripotent stem cells, we observed that Cav-1 deletion led to reduced stem cell proliferation and enhanced differentiation into neurons. This was manifested by increased neuronal dendritic tree surface area and enhanced mouse performance in contextual discrimination. Proteomic analysis revealed that Cav-1 plays a role in mitochondrial pathways in NPCs. Cav-1 localized to the mitochondria in NPCs and co-immunoprecipitated with mitofusion 2. Mitochondrial morphology was elongated in Cav-1 KO NPCs and the expression of mitofusion 2 was increased in mitochondrial fractions. Restoration of Cav-1 levels rescued elongated mitochondrial morphology and altered neuronal differentiation in Cav-1 KO NPCs. Together, this study identifies Cav-1 as a novel regulator of neurogenesis and -dependent learning and memory. Significance StatementThe hippocampal dentate gyrus (DG) orchestrates adult hippocampal neurogenesis (AHN). The precise mechanisms governing AHN remain elusive. Caveolin-1 regulates neurogenesis through mitochondrial fission-fusion process, suggesting Caveolin-1 as a novel regulator of AHN and underscoring the impact of AHN on cognition.

neuroscience↗

In vitro investigation of antibacterial activity of Gum Arabic prepared by two different processing methods against Enterococcus faecalis

BackgroundEntrococcus faecalis is a known cause of endodontic treatment failure. Synthetic drugs have been preferred for decades, but recently, many plants have been reported for their antibacterial activity. AimTo investigate the antibacterial effect of Gum Arabic (GA) processed with two different processing methods against Enterococcus faecalis. MethodAntibacterial susceptibility tests against Enterococcus faecalis (ATCC 29212) were performed for 200mg/ml ethanolic extracts of spray-dried and mechanically ground GA using Agar disc diffusion. Sodium Hypochlorite (1%), Chlorhexidine (0.2%), and Antibiotic multi-disc were used as positive controls, and ethanol (20%) as a negative. The inhibition zones diameters were measured. Serial dilutions of both types of Gum Arabic (100, 50, 25, 12.5 mg/ml) were tested for their antibacterial activity. ResultsIn Concentration 200 mg/ml, spray-dried GA displayed a significantly greater inhibition zone against E. faecalis than mechanically ground (P=0.02). Both types of Gum Arabic exhibited lower antibacterial activity than chlorhexidine (0.2%). However, only mechanically ground GA showed significant result (P=0.005). Spray-dried GA showed significantly higher antibacterial activity against than Tetracycline 300mcg (P=0.005). The antibacterial activity of spray-dried GA exceeded that of mechanically ground in all concentrations of serial dilutions, except for 12.5mg/ml, both are similar. Conclusionprocessing method of Gum Arabic affects its antibacterial potency against E. faecalis. In high concentrations, spray-dried GA is active antibacterial, while mechanically ground is non-active. Decreasing the concentration of mechanically ground GA increases its inhibitory effect, but the opposite effect was observed with spray-dried GA.

microbiology↗

A survey of proteomic variation across two ethnic groups in Nigeria and its relationship to obesity risk

Proteomic variation between individuals has immense potential for identifying novel drug targets and disease mechanisms. However, with high-throughput proteomic technologies still in their infancy, they have largely been applied in large majority European ancestry cohorts (e.g. the UK Biobank). An open question is the degree to which proteomic signatures seen in European and other groups mirror those seen in diverse populations, such as cohorts from Africa. Coupled with genetic information, we can also gain a better understanding of the role of genetic variants in the regulation of the proteome and subsequent disease mechanisms. To address the gap in our understanding of proteomic variation in individuals of African ancestry, we collected proteomic data from 176 individuals across two ethnic groups (Igbo and Yoruba) in Nigeria. These individuals were also stratified into high BMI (BMI > 30 kg/m2) and normal BMI (20 kg/m2 < BMI < 30 kg/m2) categories. We characterized differences in plasma protein abundance using the Olink Explore 1536 panel between high and normal BMI individuals, finding strong associations consistent with previously known signals in individuals of European descent. We additionally found 73 sentinel cis-pQTL in this dataset, with 21 lead cis-pQTL not observed in catalogs of variation from European-ancestry individuals. In summary, our study highlights the value of leveraging proteomic data in cohorts of diverse ancestry for investigating trait-specific mechanisms and discovering novel genetic regulators of the plasma proteome.

genomics↗

Loss of spatacsin impairs cholesterol trafficking and calcium homeostasis

Mutations in SPG11, leading to loss of spatacsin function, impair the formation of membrane tubules in lysosomes and cause the accumulation of lipids in lysosome compartment. However, the full nature of lipids accumulating in lysosomes and the physiological consequences of such accumulation are not known. Here we show that loss of spatacsin, but also downregulation of clathrin, inhibited the formation of tubules on late endosomes/lysosomes and prevented the clearance of cholesterol from this subcellular compartment. Using spatacsin-deficient cells, we evaluated the consequences of impaired cholesterol clearance from late endosomes/lysosomes. The accumulation of cholesterol in late endosomes/lysosomes led to lower cholesterol levels in the plasma membrane, enhancing the entry of extracellular calcium by store-operated calcium entry and increasing resting cytosolic calcium levels. Higher cytosolic calcium levels promoted the nuclear translocation of the master regulator of lysosomes TFEB. Downregulation of TFEB or decrease in resting calcium levels in absence of spatacsin partially corrected the formation of tubules and the accumulation of cholesterol in lysosomes, suggesting that spatacsin could be indirectly implicated in the formation of tubules. Our work reveals a homeostatic balance between cholesterol trafficking and cytosolic calcium levels and shows that loss of spatacsin impairs this homeostatic equilibrium.

cell biology↗