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Abstract Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria‐derived activator of caspase/direct inhibitor of apoptosis‐binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase‐2 and wingless‐related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin‐dependent kinase 2 and cyclin‐dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y‐box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal‐regulated kinase 1/2, and disrupting the repair process of DNA double‐strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit α (PIK3CA)‐mutant CRC, resulting in a reduction in phosphatidylinositol‐3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

Abstract Background The gut microbiota plays a crucial role in regulating the host’s immune responses during aging, which was characterized by a different abundance of bacteria in several age groups. Main body Gut microbiota dysbiosis is associated with aging, antibiotic exposure, underlying diseases, infections, hormonal variations, circadian rhythm, and malnutrition, either singularly or in combination. The appropriate use of prebiotics and probiotics may be able to prevent or reduce this disruption. Conclusion The current review focuses on the gut microbiota composition across the life cycle, factors affecting gut microbiota changes with aging, and interventions to modulate gut microbiota.

Maryam AM Elsaid,1 Shady Soliman,2 Omar Hashem2 1Department of Clinical Electrophysiology of Vision, Research Institute of Ophthalmology, Giza, Egypt; 2Department of Cornea and Refractive, Research Institute of Ophthalmology, Giza, EgyptCorrespondence: Omar Hashem, Department of Cornea and Refractive, Research institute of Ophthalmology, Giza, Egypt, Tel +201222422032, Email hashemomar@yahoo.comPurpose: This study compared flash visual evoked potentials (VEPs) parameter differences between eyes with unilateral opaque media and their normal contralateral counterparts.Patients and Methods: We included 178 patients with unilateral media opacity and normal contralateral eye in each patient. The diseased eyes had normal ultrasonographic findings and were candidates for keratoplasty or anterior segment reconstruction. The patients underwent electrophysiological testing by the flash VEPs recording with the use of 1.4Hz (transient) and 8Hz (flicker) frequencies.Results: The medians of P2 implicit times were significantly higher in eyes with media opacity than in normal eyes, with median differences between both eyes of − 6.7 ms. Furthermore, the median N2P2 amplitude was 9.70 μv with media opacity compared with 11.00 μv in the normal eyes, with a significant difference of 1.3 (p = 0.002). The flash VEPs median parameters recorded at a frequency of 8-Hz showed significant differences in medians of spectral plots of 0.6 μv between normal and abnormal eyes. The same for the signal-to-noise ratio, where the difference in medians was 3 dB. Analysis of the difference between both eyes (normal–abnormal) in each patient showed in P2 implicit time a difference range of − 49 to 54.7 ms with a median difference of − 3 ms. The difference in amplitudes of recorded N2P2 showed a median of 2.13 μv. There was a statistically significant but weak negative correlation between N2P2 amplitude (r spearman = − 0.173, p = 0.021) and the grades of corneal opacity.Conclusion: Preoperative flash VEPs recording is useful for evaluating visual function in patients with unilateral media opacity to determine the future benefits of keratoplasty or anterior segment reconstruction. There are no correlations between the flash VEP parameters or the difference between the 2 eyes and the grades of corneal opacity.Keywords: corneal opacity, keratoplasty, flash visual evoked potential, unilateral

Abstract According to recent studies on the benefits of natural polymer-based hydrogels in biomedical applications, gellan gum (GG)/acacia gum (AG) hydrogel was prepared in this study. In order to regulate the mechanical behavior of the hydrogel, graphite carbon nitride (g-C3N4) was included in the hydrogel matrix. In addition, metal oxide nanoparticles ZnCuFe2O4 were added to the composite for antibacterial activity. The prepared GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite was characterized by using FE-SEM, FTIR, EDX, XRD and TGA. The nanobiocomposite exhibited spherical morphology, which was related to the incorporation of the metal oxide nanoparticles. GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite showed 95.11%, 92.73% and 88.97% biocompatibility toward HEK293T cell lines within 24 h, 48 h and 72 h incubation, respectively, which indicates that this nanobiocomposite is completely biocompatible with healthy cells. Also, the nanobiocomposite was able to inhibit Pseudomonas aeruginosa biofilm growth on its surface up to 87%. Rheological studies showed that the nanobiocomposite has a viscoelastic structure and has a water uptake ratio of 93.2%. In comparison with other similar studies, this nanobiocomposite has exhibited superior antibacterial activity complete biocompatibility and proper mechanical properties, high swelling and water absorption capability. These results indicate that GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanocomposite can be considered as a potential candidate for biomedical applications such as tissue engineering and wound healing.

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development.Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model.Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195.Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

Abstract Background Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer. Methods A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions. Results We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5. Conclusions PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.

Omar Hashem,1 Hosam Sheha2,3 1Cornea and Refractive Department, Research Institute of Ophthalmology, Giza, Cairo, Egypt; 2Department of Ophthalmology, Florida International University, Herbert Wertheim College of Medicine & Glaucoma Research Organization, Miami, FL, USA; 3Department of Ophthalmology, Manhattan Eye, Ear and Throat Hospital, Hofstra Northwell School of Medicine, New York, NY, USACorrespondence: Omar Hashem, Research Institute of Ophthalmology, 2 Al Ahram Street, Giza, Cairo, Egypt, Tel +201222422032, Email Hashemomar@yahoo.comPurpose: To evaluate long-term safety, effectiveness, and stability of unilateral LASIK in pediatric myopic anisometropic amblyopia.Methods: This retrospective study included children who received unilateral LASIK for myopic anisometropia of > 6 D, after mandatory 6-month occlusion/penalization therapy. They were evaluated at 6 months, 1 year, 2 years and biannually until 10 years. Outcome measures included visual acuity, refraction, ocular alignment, stereopsis, corneal clarity, and corneal topography.Results: 32 patients (16 girls) with mean age of 8.6 ± 2.3 years completed 10 years of follow up after unilateral LASIK. Mean preoperative spherical equivalent refraction (SER) was − 10.3D ± 2.0D in the affected eye, with anisometropic difference of − 9.5D ± 1.7D. Mean post-LASIK SER was − 1.3D± 0.8D (p< 0.001). Anisometropia significantly decreased to 0.3D± 0.8D, 0.4D± 1.0D, and 1.0± 2.5D at 6 months, 1 year and 10 years respectively (p< 0.001). 11 patients (34%) who had preoperative intermittent exotropia (< 15°) regained orthophoria in all gazes, while 5 of 10 who had constant exotropia with large angle (> 30°) required strabismus surgery for ocular alignment. BCVA improved from 0.04± 0.6 Decimal at baseline to 0.6 ± 0.2 after LASIK and occlusion therapy (p< 0.001). Despite insignificant refractive regression in both eyes, patients have maintained orthophoria, improved stereopsis, clear cornea, and the topography showed no evidence of post-LASIK ectasia.Conclusion: LASIK appears safe, effective, and stable for correcting refractory pediatric myopic anisometropia, in which conventional measures fail or endanger normal visual development. Eliminating anisometropic aniseikonia consequently restores binocular vision and stereopsis which, along with amblyopia therapy, would reverse amblyopia and prevent recurrence.Keywords: amblyopia, aniseikonia, LASIK, pediatric myopic anisometropia

Elizabeth Yeu,1,2 Omar Hashem,3 Hosam Sheha3– 5 1Virginia Eye Consultants, Norfolk, VA, USA; 2Eastern Virginia Medical School, Norfolk, VA, USA; 3Research Institute of Ophthalmology, Cairo, Egypt; 4Florida International University Herbert Wertheim College of Medicine, & Glaucoma Research Organization, Miami, FL, USA; 5Manhattan Eye, Ear and Throat Hospital, Hofstra Northwell School of Medicine, New York, NY, USACorrespondence: Hosam Sheha, Department of Ophthalmology, Manhattan Eye, Ear and Throat Hospital, 210 E 64 Street, New York, NY, 10065, USA, Tel +1 917-810-9555, Email hoss88@gmail.comPurpose: To assess the effectiveness of cryopreserved amniotic membrane (CAM) after debridement in treating epithelial basement membrane dystrophy (EBMD) prior to cataract surgery.Methods: This pilot study included 2 treatment groups: a prospective study group of 9 subjects with significant EBMD who received debridement followed by self-retained CAM, and a retrospective, control group of 10 consecutive subjects who received debridement followed by a bandage contact lens (BCL). Slit-lamp photography after fluorescein staining were used to monitor healing. Corneal topography and IOL calculation were compared at baseline and 1 month after the procedure. Refraction and ocular surface stability were also compared after cataract surgery.Results: Corneal reepithelialization after debridement occurred in 4.6 ± 0.8 days in the study group and 6.8 ± 0.6 days in the control (p < 0.05). Corneal topography showed changes in curvature from 43.5 ± 1.2D at baseline to 44.6 ± 1.2D at 1 month in the study group and from 45.0 ± 0.6D to 45.7 ± 0.8D in the control (p = 0.38). Average change in IOL calculation was 1.56 D in the study group, compared to 0.95 D in control (p = 0.29). Post-cataract refraction in both groups was within ± 0.5 Diopter of the anticipated, and corneal surface remained stable without EBMD recurrence.Conclusion: Management of ocular surface disorders prior to cataract surgery stabilizes IOL calculation and reduces postoperative refractive surprises. CAM relatively accelerated healing after debridement; however, it was not better than BCL in stabilizing the ocular surface and improving visual outcome. The use of CAM in cases of EBMD remains speculative.Keywords: amniotic membrane, cataract, EBMD, ocular surface

Sameh G Taher,1 Mahmoud A Rageh,1 Omar Hashem2 1Department of Pediatric Ophthalmology and Strabismus, Research Institute of Ophthalmology, Giza, Egypt; 2Department of Cornea and Refractive Surgery, Research Institute of Ophthalmology, Giza, EgyptCorrespondence: Omar HashemDepartment of Cornea and Refractive Surgery, Research Institute of Ophthalmology, 2 El Ahram St, Giza, EgyptTel +201222422032Email hashemomar@yahoo.com; omar.hashim004@gmail.comPurpose: This study aimed to evaluate the efficacy and safety of fenestration in comparison to the classic muscle recession as a weakening maneuver to horizontal and vertical extra ocular muscles in the surgical management of strabismus.Patients and Methods: This is a pilot single blind parallel group randomized controlled trial with 1:1 allocation ratio. Male or female patients aged 1- to 60-years-old who were admitted to the Pediatric Ophthalmology and Strabismus Department for surgical correction of horizontal or vertical strabismus. Patients were randomly allocated by the envelop method to either group 1 (muscle fenestration, N=9) or group 2 (classic muscle recession, N=9). All participants were assessed at the first post operative day, at one week, and one month after the surgery for the outcomes.Results: Postoperative ocular alignment evaluated at the first day, one week, and one month following the operation showed comparable results with no significant differences between both groups (p> 0.05). The median postoperative pain score evaluated at the first day following the operation was significantly higher in fenestration group than recession group (the medians were 2.0 and 1.0, respectively, p=0.014). Alternatively, the medians of the pain score were equal in both groups at one week and one month postoperatively (p> 0.999). One patient in the fenestration group developed progressive subconjunctival hemorrhage. In contrast, there was no postoperative complications in the recession group (p> 0.999).Conclusion: Efficacy and safety of muscle fenestration for correcting horizontal or vertical strabismus was comparable to the classic muscle recession.Keywords: adults, children, fenestration, recession, strabismus, surgery

Abstract There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.

The growth of carbon nanostructures from vegetable oils using a modified conventional approach is a simple and environmentally friendly technology with controllable features. The goal of this study is to develop a simple and environmentally friendly process for making carbon nanoparticles using commercially available, low-cost vegetable oils. The technique involves the controlled burning of “Mustard”, “Olive”, and “Linseed” oils using the traditional clay lamps and collecting the carbon soot on a ceramic plate. The prepared carbon nanoparticles were purified through sonication and subjected to characterization using powder X-ray diffraction, SEM, Fourier transformed infrared, Thermogravimetric and differential scanning calorimetric analyses. The average particle size of carbon nanoparticles as investigated by powder X-Ray Diffraction analyses was found to be 18, 24, and 57 nm for mustard, olive and linseed oils respectively. SEM analyses revealed the surface morphology of these carbon nanostructures as spherical particles. Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) providing knowledge about the thermal stability of these carbon nanoparticles. The synthesized carbon nanoparticles were screened for antibacterial activities against different species (e.g., Pseudomonas aeruginosa, Streptococcus haemolyticus, Proteus refrigere and Staphylococcus aureus) and fruitful results have been obtained.

Sulfosalts are well known naturally occurring mineral species since the surprise mineralogy and are well reported for a variety of applications including photovoltaics. In the current study Cu3BiS3 (wittichinite mineral), a member of the sulfosalt family was crystallized by a simplified route through chemical bath deposition. To elaborate the experimental design and deposition mechanism and for the sake of comparison, Bi2S3 thin films were also deposited. X-Ray Diffraction, Scanning Electron Microscopy, Atomic Force Microscopy, UV–Vis Spectroscopy, and the Hall effect were used to explore the structural, morphological, and optoelectronic behaviour of synthesized materials in the form of thin films. The thickness of the films was measured by ellipsometry. XRD analysis confirmed the Bi2S3 for the first bath, while for the rest of the films Cu3BiS3 phase emerged. Optical bandgap values of 1.0 eV and 1.25 eV were achieved for Bi2S3 and Cu3BiS3 thin films respectively. Results revealed that Cu3BiS3 thin films deposited for 6 h at room temperature demonstrated Hall mobility of 34.9 cm2 v−1 s−1, the charge carrier concentration of 6.07 × 1016 cm−3 and 7.22 O-cm resistivity with the thickness of 126 nm, hence validating the potential of synthesized materials for photovoltaic applications.