Search Results (46)

Background/Objectives: Work-related musculoskeletal disorders (WMSDs) experienced by employees are the cause of significant issues and costs for companies. At PNU, understanding of the risk factors contributing to this pain is limited, impeding the development of effective solutions. To address this, it is important to examine various factors such as sociodemographics, ergonomics, psychology, and job satisfaction. By investigating these factors, PNU can create targeted interventions to improve worker health and reduce musculoskeletal pain. Methods: A cross-sectional study was conducted among 150 female staff members at the health colleges of Princess Nourah bint Abdulrahman University in Saudi Arabia, employing a multistage sampling technique. Data were collected from 20 December to 4 April 2024 using a standardized Google Forms questionnaire. Data analysis was performed using JMP software (version 14). Results: The results show a high prevalence of musculoskeletal pain among participants, with the analysis identifying several individual, ergonomic, and psychosocial risk factors that significantly correlated with reported pain, including prolonged sitting, poor posture, job stress, and low job satisfaction. Conclusions: Musculoskeletal disorders are prevalent among staff members, with ergonomic and psychosocial factors playing a significant role. Interventions targeting these risk factors are essential to improving occupational health and staff productivity. Full article

Background/Objectives: Linezolid is a first-in-class oxazolidinone antibiotic that exhibits activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, its clinical use is often restricted because of hematological toxicities, particularly thrombocytopenia, in patients with renal impairment. That side effect is thought to result from the systemic accumulation of pharmacologically inactive metabolites generated by oxidative degradation and ring-opening of the morpholine, but the details remain unclear. In this study, we established a novel synthetic route for four linezolid metabolites (PNU-142618, 142300, 142586 and 173558). Methods: The four major metabolites, which are secondary or tertiary amines, were synthesized using the aniline derivatives protected with a 2-nitrobenzensulfonyl (Ns) group. Results: Application of this Ns strategy enabled selective N-alkylation, enabling efficient synthesis of the target metabolites. The desired metabolites containing a carboxylic acid group were obtained as their sodium salts. This is the first report on the synthesis of PNU-142618 and 173558. Conclusions: The established synthetic pathway provides access to four linezolid metabolites. The results facilitated the provision of compounds necessary for comprehensive pharmacokinetic and toxicological studies. Full article

Nicotinamide adenine dinucleotide (NAD⁺) serves as a critical cofactor in redox reactions and metabolic transformations catalyzed by NAD-dependent enzymes and is essential for bacterial survival and virulence. The biosynthesis of NAD⁺ in the cariogenic pathogen Streptococcus Sobrinus (S. sobrinus), a pivotal participant in oral cavities of children and adolescents with a history of caries, has yet to be explored. Bioinformatics, genetics, and biochemical techniques were used to identify NAD⁺ biosynthesis pathways and corresponding regulator in S. Sobrinus. S. sobrinus lacks de novo NAD⁺ synthesis pathway but comprises NA and Nam salvage pathway I (PncA-PncB-NadD-NadE) and PnuC-NadR salvage pathway III. NiaY and PnuC were involved in the salvage pathways. N-terminal domain of SsNrtR regulator was identified as DNA-binding domain binding to the pnuC and pncB probe, and addition of ADP-ribose reversed the binding of SsNrtR to the target promoters to regulate NAD⁺ salvage pathways. C-terminal domain of SsNrtR was non-catalytic, consistent with loss of Nudix motif conservation. Furthermore, the abrogation of niaR compromised multiple pathogenic traits, including cellular proliferation, acidogenesis, and the architecture/mechanical integrity of biofilms. Consequently, this mutant exhibited attenuated virulence in a rat caries model. Our findings conclusively demonstrate that SsNrtR-mediated regulation of NAD⁺ homeostasis is a critical determinant of the cariogenic potential of S. sobrinus. This study identifies SsNrtR as a previously uncharacterized NAD⁺-responsive regulator that integrates metabolic homeostasis with the control of virulence in Streptococcus sobrinus. These findings elucidate a novel metabolic–virulence regulatory axis in this species and position SsNrtR as a promising target for the development of anti-caries interventions. Full article

Background: The Wnt/β-catenin signaling pathway plays a pivotal role in embryonic development, maintenance of the central nervous system, and the formation of neuronal circuits. Disruption of this pathway is closely associated with oncogenesis and neurodegenerative diseases, notably Alzheimer’s disease. Flavonoids such as quercetin derivatives have emerged as promising neuroprotective agents. This study investigates the impact of 3-O-methylquercetin (3OMQ), a methylated quercetin metabolite, on Wnt/β-catenin signaling and its potential relevance in neurodegenerative disease models. Methods: The ability of 3OMQ to modulate Wnt/β-catenin activity was analyzed using a luciferase-based reporter assay in both neural and non-neural cell lines. Cell viability assays evaluated cytotoxicity at various concentrations. We mapped 3OMQ activity within the pathway using targeted cell signaling experiments. Docking and molecular dynamics simulations suggested glycogen synthase kinase 3β (GSK3β) as a putative target of 3OMQ. Finally, we employed a mouse model of acute amyloid-β oligomer (AβO) toxicity to assess the in vivo effects of 3OMQ on spatial memory and Wnt-related gene expression. Results: We compared the flavonoids quercitrin, quercetin, and 3-O-methylquercitrin (3OMQ) with pharmacologically active compounds in a gene reporter assay (TOPFLASH) using Wnt-sensitive RKO cells treated with Wnt3a-conditioned medium. XAV-939 and PNU-74654 showed inhibitory activity, while BIO, CHIR99021, quercitrin, and 3OMQ enhanced the Wnt/β-catenin pathway. Notably, 3OMQ potentiated this pathway at concentrations 5–10 times lower than quercitrin and outperformed 1 μM BIO at 10 μM without cytotoxicity, highlighting its remarkable potency. Mechanistically, 3OMQ acts downstream of initial membrane activation and upstream of the β-catenin destruction complex. Consistently, molecular docking indicates a strong interaction with GSK3, a central regulator of the pathway. In adult mice, 3OMQ administration prevented AβO-induced recognition memory deficits and favored normalization of Wnt-related gene expression. Conclusions: These findings identify 3OMQ as a potent positive modulator of the Wnt/β-catenin pathway, with both in vitro and in vivo neuroprotective effects. Targeting Wnt signaling with compounds such as 3OMQ holds promise for maintaining neuronal health and developing therapeutic strategies for neurodegenerative conditions. Full article

A micro-pulse detonation engine (μPDE) was designed and installed to a direct-connect scramjet combustor of Pusan National University (PNU-DCSC). The active excitation on the scramjet combustor was experimentally studied using the μPDE operating at frequencies of 10–20 Hz. A vitiation air heater (VAH) was used to supply high-enthalpy vitiated air to the isolator and the scramjet combustor at a Mach number of 2.0, with a total temperature of 1600 K and a total pressure of 1.68 MPa. The exit of μPDE was located at the center of the cavity of the scramjet combustor. Active excitation was performed at equivalence ratios of 0.111 and 0.163, and characteristics were analyzed through Schlieren recording and bottom wall pressure measurement. As a result, when the detonation emitted from the μPDE entered the scramjet combustor, it instantly formed a shock train and moved forward within the scramjet combustor. The flame instantaneously changed from the cavity shear layer flame to the cavity flame. Through bottom wall pressure measurement, it was also observed that active excitation resulted in a significant pressure increase near the cavity compared to when active excitation was not performed. This revealed combustion characteristics, indicating improved combustion efficiency from the pressure increase in the scramjet combustor. Full article

Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of α7 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an α7 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction. The effects of ANA12, a TrkB receptor antagonist, on LPS-induced cognitive deficit and depressive-like behaviors were determined using the Y-maze, tail suspension test (TST), and forced swim test (FST). Pharmacological interactions between PNU120596 and ANA12 were also examined. Experiments were conducted in male C57BL/6J mice. LPS administration (1 mg/kg) resulted in increased expression of BDNF and the NKCC1/KCC2 ratio and decreased expression of KCC2 in the hippocampus and prefrontal cortex. PNU120596 pretreatment (4 mg/kg) attenuated the LPS-induced increase in the expression of BDNF and NKCC1/KCC2 ratio and the reduction in KCC2 expression in these brain regions. In addition, ANA12 (0.25 or 0.50 mg/kg) reduced the LPS-induced cognitive deficit and depressive-like behaviors measured by a reduced spontaneous alternation in the Y-maze and increased immobility duration in TST and FST. Coadministration of PNU120596 (1 mg/kg) and ANA12 (0.25 mg/kg) prevented the LPS-induced cognitive deficit and depressive-like behaviors. Overall, PNU120596 prevented the LPS-induced depressive-like behavior by likely decreasing neuronal excitability via targeting microglial α7 nAChR in the hippocampus and prefrontal cortex. Full article

The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus, αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs. We tested the synthetic αCtx-AtIA using the calcium imaging-based Constellation Pharmacology assay on mouse DRG neurons and found that αCtx-AtIA significantly inhibited ACh-induced calcium influx in the presence of an α7 positive allosteric modulator, PNU-120596 (PNU). However, αCtx-AtIA did not display any activity in the absence of PNU. These findings were further validated using two-electrode voltage clamp electrophysiology performed on oocytes overexpressing mouse α3β4, α6/α3β4 and α7 nAChRs subtypes. We observed that αCtx-AtIA displayed no or low potency in blocking α3β4 and α6/α3β4 receptors, respectively, but improved potency and selectivity to block α7 nAChRs when compared with αCtx-PeIA. Through the synthesis of two additional analogs of αCtx-AtIA and subsequent characterization using Constellation Pharmacology, we were able to identify residue Trp18 as a major contributor to the activity of the peptide. Full article

Background: Multi-comminuted, intra-articular fractures of the distal humerus still pose a challenge to modern orthopedics due to unsatisfactory treatment results and a high percentage (over 50%) of postoperative complications. When surgical treatment is chosen, such fractures are fixed using two plates with locking screws, which can be used in three spatial configurations: either parallel or one of two perpendicular variants (posterolateral and posteromedial). The evaluation of the fracture healing conditions for these plate configurations is unambiguous. The contradictions between the conclusions of biomechanical studies and clinical observations were the motivation to undertake a more in-depth biomechanical analysis aiming to indicate the weak points of two-plate fracture stabilization. Methods: Research was conducted using the finite element method based on an experimentally validated model. Three variants of distal humerus fracture (Y, λ, and H) were fixed using three different plate configurations (parallel, posterolateral, and posteromedial), and they were analyzed under six loading conditions, covering the whole range of flexion in the elbow joint (0–145°). A joint reaction force equal to 150 N was assumed, which corresponds with holding a weight of 1 kg in the hand. The biomechanical conditions of bone union were assessed based on the interfragmentary movement (IFM) and using criteria formulated by Steiner et al. Results: The IFMs were established for particular regions of all of the analyzed types of fracture, with distinction to the normal and tangential components. In general, the tangential component of IFM was greater than normal. A strong influence of the elbow joint’s angular position on the IFM was observed, with excessive values occurring for flexion angles greater than 90°. In most cases, the smallest IFM values were obtained for the parallel plaiting, while the greatest values were obtained for the posteromedial plating. Based on IFM values, fracture healing conditions in particular cases (fracture type, plate configuration, loading condition, and fracture gap localization) were classified into one of four groups: optimal bone union (OPT), probable union (PU), probable non-union (PNU), and non-union (NU). Conclusions: No plating configuration is able to ensure distal humerus fracture union when the full elbow flexion is allowed while holding a weight of 1 kg in the hand. However, flexion in the range of 0–90° with such loadings is acceptable when using parallel plating, which is a positive finding in the context of the early rehabilitation process. In general, parallel plating ensures better conditions for fracture healing than perpendicular plate configurations, especially the posteromedial version. Full article

Lifestyle behaviors are daily habits influenced by social and environmental factors. This study examined lifestyle behaviors and their associations with sociodemographics, comorbidities, and pain in Saudi university students during the academic year 2021 and 2022. All students received the study invitation via university emails to complete an online questionnaire. The questionnaire included four sections (sociodemographics, health-related information, desired health promotion activities, and a lifestyle behavior assessment) via Health-Promoting Lifestyle Profile II (HPLP-II). The associations between study variables were assessed using Pearson’s correlation and multiple linear regression. The study questionnaire was completed by 1112 students. No correlation was found between sociodemographics and lifestyle-behavior-related factors except for students in the College of Science who appeared to have good lifestyle behaviors (an increase in HPLP II total scores of 3.69). Students with mental health issues have poorer lifestyle behaviors and spend more time sitting (p < 0.00). Students without disabilities have lower scores in health responsibility, physical activity, nutrition, and stress management, while auditory disability specifically lowers health responsibility (p < 0.00). Pain was not associated with any assessed lifestyle behaviors. This study identified several significant correlations and differences between variables such as age, sedentary behavior, sleep duration, disability status, college major, and lifestyle behaviors among PNU students. These findings provide insights into the factors that influence students’ health-promoting behaviors and can help guide interventions for promoting healthier lifestyles on campus. Targeted health promotion strategies at an early age could help in decreasing overall noncommunicable disease incidents later in life. The study results should be interpreted taking into consideration that the collected data were cross-sectional and self-reported. In conclusion, the findings of this study clearly demonstrate the need for specific lifestyle and health-promoting programs that are directed toward university students. Full article

Climate control in a pixel non-uniformity metro system includes regulating the air, humidity, and temperature quality within metro trains and stations to ensure passenger comfort and safety. The climate control system in a PNU metro system combines intelligent algorithms, energy-efficient practices, and advanced technologies to make a healthy and comfortable environment for passengers while reducing energy consumption. The proposed an automated climate control using an improved salp swarm algorithm with an optimal ensemble learning technique examines the underlying factors, including indoor air temperature, wind direction, indoor air relative humidity, light sensor 1 (wavelength), return air relative humidity, supply air temperature, wind speed, supply air relative humidity, airflow rate, and return air temperature. Moreover, this new proposed technique applies ISSA to elect an optimal set of features. Then, the climate control process takes place using an ensemble learning approach comprising long short-term memory, gated recurrent unit, and recurrent neural network. Lastly, the Harris hawks optimization algorithm can be employed to adjust the hyperparameters related to the ensemble learning models. The extensive results demonstrated the supremacy of the proposed algorithms over other approaches to the climate control process on PNU metro systems. Full article

Background and Objectives: PNU-74654, a Wnt/β-catenin pathway inhibitor, has an antiproliferative effect on many cancer types; however, its therapeutic role in pancreatic cancer (PC) has not yet been demonstrated. Here, the effects of PNU-74654 on proliferation and cell cycle phase distribution were studied in PC cell lines. Materials and Methods: The cancer-related molecular pathways regulated by PNU-74654 were determined by a proteome profiling oncology array and confirmed by western blotting. Results: The cell viability and proliferative ability of PC cells were decreased by PNU-74654 treatment. G1 arrest was observed, as indicated by the downregulation of cyclin E and cyclin-dependent kinase 2 (CDK2) and the upregulation of p27. PNU-74654 inhibited the epithelial–mesenchymal transition (EMT), as determined by an increase in E-cadherin and decreases in N-cadherin, ZEB1, and hypoxia-inducible factor-1 alpha (HIF-1α). PNU-74654 also suppressed cytoplasmic and nuclear β-catenin and impaired the NF-κB pathway. Conclusions: These results demonstrate that PNU-74654 modulates G1/S regulatory proteins and inhibits the EMT, thereby suppressing PC cell proliferation, migration, and invasion. The synergistic effect of PNU-74654 and chemotherapy or the exclusive use of PNU-74654 may be therapeutic options for PC and require further investigation. Full article

This experimental investigation focused on the ignition and combustion characteristics of a tandem cavity-based scramjet combustor with side-by-side identical cavities. This study utilized the Pusan National University-direct connect scramjet combustor (PNU-DCSC), which was capable of simulating flight conditions at Mach number 4.0–5.0 and altitudes of 20–25 km using the vitiated air heater (VAH). The combustion tests were conducted under off-design point conditions corresponding to low inlet enthalpy. It is a condition in which self-ignition does not occur, and a micro pulse detonation engine (μPDE) ignitor is used. The results revealed that as the injection pressure of the gaseous hydrogen fuel (GH₂) and the corresponding equivalence ratio increased, the combustion mode transitioned from the cavity-shear layer flame to the jet-wake flame. Furthermore, the measured wall static pressure profiles along the isolator and scramjet combustor indicated that the region of elevated pressure distribution caused by the shock train expanded upstream with higher equivalence ratios. When ignited from the secondary cavity, the combustion area did not extend to the primary cavity at lower equivalence ratios, while it expanded upstream faster with higher equivalence ratios. Therefore, the combustion characteristics of the tandem cavity were found to vary based on the overall equivalence ratio of the main fuel (GH₂) and ignition position. Full article

Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC₅₀ of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs with increased potency using virtual screening of their binding to the α7 nAChR molecular model. Fourteen designed analogs were synthesized and tested in vitro by calcium fluorescence assay on the α7 nAChR expressed in neuro 2a cells, methoxy ester of D-6-iodohypaphorine (6ID) showing the highest potency (EC₅₀ 610 nM), being almost inactive toward α9α10 nAChR. The macrophages cytometry revealed an anti-inflammatory activity, decreasing the expression of TLR4 and increasing CD86, similarly to the action of PNU282987, a selective α7 nAChR agonist. 6ID administration in doses 0.1 and 0.5 mg/kg decreased carrageenan-induced allodynia and hyperalgesia in rodents, in accord with its anti-inflammatory action. Methoxy ester of D-6-nitrohypaphorine demonstrated anti-oedemic and analgesic effects in arthritis rat model at i.p. doses 0.05–0.26 mg/kg. Tested compounds showed excellent tolerability with no acute in vivo toxicity in dosages up to 100 mg/kg i.p. Thus, combining molecular modelling and natural product-inspired drug design improved the desired activity of the chosen nAChR ligand. Full article

Attitudes and feelings towards food waste and positions on management policies have been vastly increased over the past few decades. Most of the available research on the analysis of attitudes towards food waste have been carried out using conventional statistical methods. This paper aims to assess and analyse attitudes and preferences of young Saudi females towards a number of policies and plans that are designed to meeting sustainable targets, using fuzzy logic analysis. This is a very important aim, especially since Vision 2030 in Saudi Arabia puts a major emphasis on sustainability, setting many resources to tackle environmental problems and achieving better social standards. The Methodology includes designing and collecting data from 199 participants using a questionnaire that includes 23 questions. Data were obtained from students at Princess Nourah bint Abdulrahman University (PNU). The analysis includes utilising artificial intelligence (AI) techniques. Fuzzy logic analysis has been widely used in many fields, but has not seen many applications on food waste analysis and attitudes. Fuzzy logic analysis has the advantage of producing efficient results from smaller sample sizes and, in particular, with qualitative characteristics of the used indicators. The participants expressed positive preferences and attitudes towards the programs and policies that are designed to achieve sustainability and manage food waste. The results show that over 25% of them prefer the option of “storage for reuse” of food waste, over 35% prefer the option of distribute it to needed families and over 30% opted to the option of recycling to fertilisers. The study also reveals a very good level of awareness and appreciation of food waste and plans associated with it. The implications from this study suggest that despite the positive attitudes, there still is more research needed to obtain full understanding of attitudes towards food waste from the whole range of the population in order to gain knowledge and build specific programs to reduce food waste and achieve sustainability in the country. Full article

Migraine is a highly disabling pain disorder with huge socioeconomic and personal costs. It is genetically heterogenous leading to variability in response to current treatments and frequent lack of response. Thus, new treatment strategies are needed. A combination of preclinical and clinical data indicate that ATP-sensitive potassium (K_ATP) channel inhibitors could be novel and highly effective drugs in the treatment of migraine. The subtype Kir6.1/SUR2B is of particular interest and inhibitors specific for this cranio-vascular K_ATP channel subtype may qualify as future migraine drugs. Historically, different technologies and methods have been undertaken to characterize K_ATP channel modulators and, therefore, a head-to-head comparison of potency and selectivity between the different K_ATP subtypes is difficult to assess. Here, we characterize available K_ATP channel activators and inhibitors in fluorescence-based thallium-flux assays using HEK293 cells stably expressing human Kir6.1/SUR2B, Kir6.2/SUR1, and Kir6.2/SUR2A K_ATP channels. Among the openers tested, levcromakalim, Y-26763, pinacidil, P-1075, ZM226600, ZD0947, and A-278637 showed preference for the K_ATP channel subtype Kir6.1/SUR2B, whereas BMS-191095, NN414, and VU0071306 demonstrated preferred activation of the Kir6.2/SUR1 subtype. In the group of K_ATP channel blockers, only Rosiglitazone and PNU-37783A showed selective inhibition of the Kir6.1/SUR2B subtype. PNU-37783A was stopped in clinical development and Rosiglitazone has a low potency for the vascular K_ATP channel subtype. Therefore, development of novel selective K_ATP channel blockers, having a benign side effect profile, are needed to clinically prove inhibition of Kir6.1/SUR2B as an effective migraine treatment. Full article