Dr Mohammed Mahmoud Youssif

This paper addresses the integration of quantity, quality, and maintenance challenges in a serial multistage manufacturing system. This research presents a comprehensive joint optimization model that extensively considers the interdependencies among these aspects. The model encompasses buffer allocation, which efficiently manages stochastic processing times, part quality inspection planning to detect and minimize defects, and preventative maintenance strategies to mitigate machine deterioration. By integrating these functions, the manufacturing system can significantly improve its overall performance and reduce costs, with research results showing an average cost reduction of 15%. The proposed model formulates a stochastic mixed integer nonlinear programming problem, which is NP-hard and combinatorial. To address this problem, a comprehensive solution approach is employed, combining a genetic algorithm as the primary generative method with hybrid genetic algorithm variations. Additionally, simulation (recursive approach) serves as the evaluative method. Computational experiments are conducted to validate and optimize the proposed model. The findings make a substantial contribution to the existing body of knowledge, offering a robust solution that enhances performance and reduces costs in addressing quantity, quality, and maintenance challenges in a serial multistage manufacturing system. Finally, a discussion of the research results, their implications, and applications offers valuable insights for practitioners and decision-makers aiming to optimize their production processes.

Acute kidney injury (AKI) is a common complication associated with sepsis, yet no effective treatment is currently available. The primary mechanisms involved in lipopolysaccharide (LPS)-induced septic AKI are oxidative stress, inflammation, and apoptosis. This study aimed to investigate the potential renoprotective effects of linagliptin, an antidiabetic dipeptidyl peptidase (DPP)-4 inhibitor, against LPS-induced AKI with special emphasis on renal brain-derived neurotrophic factor (BDNF)/nuclear factor erythroid 2-related factor 2 (NRF2) axis. Mice were divided into control, LPS, LPS + linagliptin, and LPS + linagliptin+ANA-12 (tropomyosin receptor kinase B (TrkB) antagonist) groups. Our results revealed that linagliptin, partially through BDNF augmentation, ameliorated AKI, evidenced by the improved histological structure and function of the kidney where serum creatinine, blood urea nitrogen, cystatin C, and renal kidney injury molecule-1were decreased with increased serum albumin. These improvements result from glucagon-like peptide-1/BDNF/TrkB-mediated NRF2 activation, enhancing antioxidant, anti-inflammatory, and antiapoptotic pathways. Linagliptin, through NRF2 augmentation, suppressed renal myeloperoxidase, malondialdehyde, NLR Family pyrin domain-containing 3 inflammasome, nuclear factor-kappaB, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, B-cell lymphoma 2 (Bcl2)-associated X protein, while boosting the antioxidant glutathione and the antiapoptotic Bcl2 contents. The administration of ANA-12 before linagliptin partially reversed these beneficial effects. Accordingly, our results suggest that linagliptin has therapeutic potential in managing LPS-induced AKI. Furthermore, they provide insights into its underlying mechanisms, highlighting renal BDNF signaling as a potential therapeutic target through downstream NRF2 enhancement and its associated antioxidant, anti-inflammatory, and antiapoptotic effects.

Lactational exposure to antibacterial medications may affect the normal development of newborns during this crucial stage and later in adult life. Linezolid (LNZ) is an oxazolidinone antibacterial drug that is effective against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Although it is relatively toxic, there is insufficient data about LNZ use during lactation. This study aimed to elucidate the impact of linezolid administration during lactation on Wistar rats' offspring. Eighteen lactating Wistar female rats were separated into three groups (n = 6): control, therapeutic, and low dose groups. The therapeutic dose group received 61.66 mg/kg of LNZ (equivalent to the human dose), while the low dose group received 15.41 mg/kg of LNZ (1/4 of the human therapeutic dose) by gavage twice daily. All lactating dams and their offspring died four days after receiving a therapeutic dose. In the low dose group, LNZ significantly reduced the body weight of lactating females and their pups. The liver tissue of the pups showed a considerable increase in malondialdehyde levels, along with a decrease in the catalase, glutathione, and superoxide dismutase activities accompanied by moderate histological alterations like congestion, and infiltration, and DNA fragmentation as indicated by comet assay. Microscopic examination of renal tissue revealed glomeruli deterioration, cellular infiltration, and intratubular protein deposits. In conclusion, this study highlights the potential risks linezolid may pose to infants during postpartum. Therefore, there is a need for preweaning monitoring and caution should be taken during breastfeeding.

Nicorandil (NIC), an antianginal agent that acts both as an opener of adenosine triphosphate-sensitive potassium (KATP) channels and a nitric oxide donor, has demonstrated protective and curative effects in various diseases. The predominance of these mechanisms varies based on the dose of NIC and the specific organ affected. This study scrutinized the possible beneficial effects of NIC in acetaminophen (APAP)-induced hepatic encephalopathy (HE) model through highlighting the role of KATP channels in mediating these effects. Forty-eight mice were randomly subdivided into four groups: control (saline), APAP model (1 g/kg, i.p.), NIC treatment (15 mg/kg/day p.o. for 14 days), and glibenclamide (GLIB "KATP blocker", 5 mg/kg/day, p.o. 1 h before NIC for 14 days). NIC significantly mitigated APAP-induced liver injury, hyperammonemia, and cognitive deficits, as evidenced by reduced serum alanine aminotransferase, aspartate aminotransferase, ammonia levels, and improved performance in Y-maze and Morris Water Maze tests. Mechanistically, NIC suppressed hippocampal glutamate, activated phosphoserine 473 protein kinase B (p-AKT(Ser473))/mammalian target of rapamycin complex 1 (mTORC1) pathway, lessened inactivation phosphorylation of eukaryotic elongation factor 2 (eEF2), upsurged brain-derived neurotrophic factor (BDNF), leading to reduced neuroinflammation proved by nuclear factor-kappa B and tumor necrosis factor-alpha suppression. Histopathological analyses revealed improved liver and hippocampal morphology, while immunohistochemistry showed reduced astrocyte activation with NIC treatment. All these effects were abolished by GLIB pre-treatment, indicating the crucial role of KATP channel. Accordingly, NIC could alleviate APAP-induced liver injury and HE mainly dependent on KATP channel opening, with resultant inhibition of glutamate signaling, activation of p-AKT/mTORC1/eEF2/BDNF trajectory, and abating hippocampal inflammation.