Search

Al Kury LT, Zeb A, Abidin ZU, et al. Drug Des Devel Ther. 2019;13:2715–2727. In the published article, there was an error in Figure 4B on page 2723. The image for Ethanol+celecoxib+mela (Piriform-PIR) was used mistakenly leading to a duplication with the Control (Piriform-PIR) images. A new image for Ethanol+celecoxib+mela (Piriform-PIR) was found from the original data and used as a replacement. The authors apologize for this error and state that this does not change the quality and scientific conclusions of the article. The correct Figure 4 is as follows. Figure 4 Effect of melatonin and celecoxib on neuronal cell death.Notes: (A) Regions of interest analyzed; (B) H&E staining showing the extent of surviving neurons in the cortex and hippocampus. Bar 50 μm, magnification 20×, n=5/group. Surviving neurons were marked by cytoplasmic swelling, scalloped neurons with intense cytoplasmic eosinophilia, and nuclear basophilia. These changes resulted from neuronal necrosis. Some cells had a shrunken appearance, along with pyknotic nuclei. Intensive neuropil vacuolation can be seen in the ethanol-only group. *Significant difference relative to control; #Significant difference relative to ethanol group; θSignificant difference relative to ethanol + melatonin. Data presented as means ± SEM. Data analyzed by one-way ANOVA followed by post hoc Bonferroni multiple comparison using GraphPad Prism 5 software. ***P

Komal Naeem,1,2,* Lina Tariq Al Kury,3 Faiza Nasar,1,* Abdullah Alattar,4 Reem Alshaman,4 Fawad Ali Shah,1 Arif-ullah Khan,1 Shupeng Li2 1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, 747424, Pakistan; 2State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518000, People’s Republic of China; 3College of Natural and Health Sciences, Zayed University, Abu Dhabi, 49153, United Arab Emirates; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, 71421, Saudi Arabia*These authors contributed equally to this workCorrespondence: Fawad Ali ShahDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Riphah International University, 7th Avenue, Sector G-7/4, Islamabad, 747424, PakistanTel +92-51-2891835-38Fax +92-51-2891471Email fawad.shah@riphah.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518000, People’s Republic of ChinaEmail lisp@pku.edu.cnPurpose: Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been well-investigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior.Methods: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression.Results: We found marked neuronal alterations in the cortex and hippocampus of LPS-intoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings.Conclusion: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.Keywords: depression, neuroinflammation, Nrf2 pathway, lipopolysaccharide, carvacrol, neurodegeneration

Naeem K, Tariq Al Kury L, Nasar F, et al. J Inflamm Res. 2021;14:1313–1329. At the authors request, the Editor and Publisher of Journal of Inflammation Research wish to retract the published article. The authors became aware of suspected duplicated images in Figures 4 and 5 and requested for the article to be retracted. Specifically, Figure 4B, Bcl-2, Hippocampus, FLX+LPS appears to have been duplicated with the same image for Figure 4C, Caspase-3, Hippocampus, CAR 20+LPS. Figure 5D, TNF-α, Cortex, LPS appears to have been duplicated with the same image for Figure 5D, TNF-α, Cortex, CAR 20+ATRA+LPS. Figure 5D, TNF-α, Cortex, ATRA+LPS appears to have been duplicated with the same image for Figure 5E, p-NFκB, Cortex, ATRA+LPS (which has been flipped). The Editor agreed with the authors retraction request and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Zulkifal Malik,1,2 Muzaffar Abbas,2 Lina Tariq Al Kury,3 Fawad Ali Shah,1 Mahboob Alam,2 Arif-ullah Khan,1 Humaira Nadeem,1 Saad Alghamdi,4 Muhammad Umar Khayam Sahibzada,5 Shupeng Li6 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 2Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan; 3College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates; 4Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan; 6State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaCorrespondence: Muzaffar AbbasFaculty of Pharmacy, Capital University of Science and Technology, Islamabad Expressway, Kahuta Road, Zone-V, Islamabad, PakistanTel +92-51-111555666Fax +92-51-4486705Email Muzaffar.abbas@cust.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Shenzhen, 518055, People’s Republic of ChinaEmail lisp@pku.edu.cnBackground: Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice.Methods: The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression was measured by enzyme-linked immunosorbent assay. Acute and sub-acute toxicity studies were conducted to evaluate the toxicity profile of compounds.Results: Treatment with the thiazolidine derivative, 1b and 1d, attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg. No motor coordination deficits were observed in animals. The compounds also reduced IL-1β expression in the spinal cord of mice. Acute and sub-acute toxicity studies revealed that both compounds were safe.Conclusion: The compounds exhibit promising activity against inflammatory pain due to their ability to produce anti-hyperalgesic and anti-allodynic effects and to inhibit IL-1β expression in the spinal cord.Keywords: inflammatory pain, IL-1β, thiazolidine derivatives, mechanical allodynia, thermal hyperalgesia

Lina T Al Kury,1 Alam Zeb,2 Zain Ul Abidin,2 Nadeem Irshad,3 Imran Malik,2 Arooj Mohsin Alvi,2 Atif Ali Khan Khalil,4 Sareer Ahmad,4 Muhammad Faheem,2 Arif-Ullah Khan,2 Fawad Ali Shah,2 Shupeng Li51College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates; 2Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 3Department of Pharmacy, Quaid-I-Azam University, Islamabad, Pakistan; 4Rehman Medical Institute, Peshawar, Pakistan; 5State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, People’s Republic of ChinaPurpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches.Methods: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis.Results: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol.Conclusion: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers.Keywords: simulation, docking, cortex, hippocampus, ethanol, neurodegeneration

Shakir Khan,1 Fahad Alam,2 Ameer Azam,2 Asad U Khan11Interdisciplinary Biotechnology Unit, 2Center of Excellence in Material Science (Nanomaterials), Aligarh Muslim University, Aligarh, IndiaAbstract: This article explores the novel gold nanoparticle–enhanced photodynamic therapy of methylene blue against recalcitrant pathogenic Candida albicans biofilm. Physiochemical (X-ray diffraction, ultraviolet-visible absorption, photon cross-correlation, FTIR, and fluorescence spectroscopy) and electron microscopy techniques were used to characterize gold nanoparticles as well as gold nanoparticle–methylene blue conjugate. A 38.2-J/cm2 energy density of 660-nm diode laser was applied for activation of gold nanoparticle–methylene blue conjugate and methylene blue against C. albicans biofilm and cells. Antibiofilm assays, confocal laser scanning, and electron microscopy were used to investigate the effects of the conjugate. Physical characteristics of the gold nanoparticles (21 ± 2.5 nm and 0.2 mg/mL) and methylene blue (20 µg/mL) conjugation were confirmed by physicochemical and electron microscopy techniques. Antibiofilm assays and microscopic studies showed significant reduction of biofilm and adverse effect against Candida cells in the presence of conjugate. Fluorescence spectroscopic study confirmed type I photo toxicity against biofilm. Gold nanoparticle conjugate–mediated photodynamic therapy may be used against nosocomially acquired refractory Candida albicans biofilm.Keywords: Candida biofilm, gold nanoparticle–methylene blue conjugate, photodynamic therapy

Asad U KhanMedical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, IndiaThis is with reference to an article published recently in your journal regarding the antibiotic activity of chitosan-coated silver nanoparticles.1 This is an inspiring move towards control of infection caused by multidrug-resistant bacteria which has become a serious problem for clinicians and physicians worldwide.2 At the moment, carbapenems are being used as the drugs of choice to combat infections. However, the emergence of carbapenem resistance has changed current remedial approaches in the management of serious infections. One of the latest enzymes, NDM-1 (New Delhi metallo-β-lactamase-1), first identified in a Swedish patient of Indian origin in 2008,3 has been key in the development of resistance to almost all antibiotics. Infection caused by NDM-1 producers is widespread on the Indian subcontinent,4 and is now emerging in the US and other countries throughout the world.5View original paper by Jena and colleagues.

Asad U KhanMedical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, IndiaConcerning the recent article published in your journal on antibiofilm surface functionalization of catheters.1 This is an admirable approach to inhibit biofilm formation on the surfaces of various implants. Currently, a number of biomedical devices and implants are commonly used in hospitals and clinics. Over the past few decades, a number of knee and hip implants have been introduced to save lives and restore quality of life. Moreover, a significant increase in the use of stents, heart valves, vascular grafts, catheters, and other implantable devices are being introduced worldwide. However, regrettably, these surfaces are prone to microbial infections and hence device-related infections have become a major source of infection which may ultimately lead to a high mortality rate in the hospital setting.2View original paper by Lellouche and colleagues.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in dorsolateral prefrontal cortex (dlPFC) - often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low frequency oscillations in sculpting motor control. Significance Statement This work offers insights into the neural mechanisms underlying executive control of movement. By employing intraoperative cortical recordings, our study uncovers the specific role of low frequency oscillations in the mid-rostral dlPFC during response inhibition. We demonstrate a topographical organization of low frequency power along the rostral-caudal axis of the dlPFC. This finding supports existing work suggesting the PFC hierarchy may be rooted in cognitive demand and extends it by showing this hierarchy can be represented by low frequency oscillations. Finally, understanding the spatial and temporal dynamics of inhibitory control may enable more effective neuromodulation therapies in the future, such as those aimed at Parkinson Disease patients to address impulsivity., (Copyright © 2024 the authors.)

Tick infestation poses an important challenge to livestock in Pakistan. Farm management practices and environmental variables can influence tick infestation prevalence in animals. To this end, a cross-sectional survey of 96 farms in four different geographical districts (24 farms from each district) was conducted in Punjab, Pakistan, between October 2021 and January 2022. An epidemiological questionnaire was designed focusing on farm management practices and their impact on tick infestations at these farms. Data were collected via in-person interviews. Regional and farm-specific variables' associations were evaluated using Pearson's chi-square test and Fischer's exact test, respectively. A multivariable logistic regression model was used to identify significant risk factors. This study identified that using soft bedding materials, e.g., wheat straw, leaf litter or plain soil posed a significant risk of tick infestation. Additionally, the absence of quarantine measures, open sheds and inadequate drainage were found as contributing factors in univariable analysis. Higher tick prevalence in the hotter seasons highlighted the influence of Punjab's extreme weather on tick infestation. Despite regular veterinary visits and the use of acaricidal drugs, the prevalence of tick infestation at these farms suggested potential drug resistance in the ticks. The study recommended establishing quarantine practices, improving farms' drainage systems and bedding and using a combination of chemical and traditional remedies to tackle drug resistance in ticks. Education and awareness programs on tick-borne diseases and control measures are advocated to reduce the tick infestation burden on animals. Further research on longitudinal studies to better understand tick population dynamics and develop effective acaricides is encouraged. This called for collaborative control efforts among farmers, veterinarians and research institutions.

Introduction: Pancreaticoduodenectomy (PD) is the only potentially curative treatment for pancreatic head adenocarcinoma. This study aimed to determine the short-term outcomes of PD performed over 1 year at a newly established hepato-pancreatico-biliary unit in Khyber Pakhtunkhwa province of Pakistan., Material and Methods: A retrospective analysis of a prospectively maintained hospital information system (HIS) was undertaken of all patients referred to the unit between May 2021 and August 2022. Data were collected from the medical records of patients in the HIS. Data were analyzed for primary location, age, complications, and operative parameters., Results: The primary sites of disease were ampulla ( n = 18, 52.9%), pancreas ( n = 11, 32.4%), and duodenum ( n = 5, 14.7%). The median duration of surgery was 7 h. 16 (47.1%) patients required blood transfusion either intraoperatively or in the perioperative period. Patients with pre-operative biliary drainage (PBD) were more likely to have multidrug-resistant positive bile cultures with a P -value of 0.2 ( n = 12 [35.3%] vs. n = 5 [14.7%]). Overall morbidity was 38.2%. The most common complications were wound infection ( n = 12, 35.3%), delayed gastric emptying ( n = 6, 17.6%), and type B pancreatic fistula ( n = 3, 8.8%). The complication rate was higher in patients with biliary stenting ( n = 11 [32.4%] vs. n = 2 [5.9%]; P = 0.06). The median length of hospital stay for patients without complications was less (6 vs. 12 days; P < 0.001). The complication rate was lower in total laparoscopic PD (TLPD) with P = 0.4 (TLPD: 2.9%, open: 23.5%, laparoscopic assisted: 11.8%). 90-day mortality was zero., Conclusion: Short-term outcomes for PD in our facility are comparable to high-volume centers. PBD can significantly increase operative time, hospital stay, and morbidity., (Copyright: © 2024 Neelma, et al.)

Photodynamic therapy (PDT) is a minimally invasive treatment showing promise against cancer and microbial infections. PDT targets tumor cells while sparing healthy tissue, reducing side effects. It induces immunogenic cell death, potentially stimulating antitumor immune responses and reducing cancer recurrence. In microbial treatment, PDT effectively combats bacteria, fungi and viruses. Combining PDT with chemotherapy, radiotherapy and immunotherapy enhances its efficacy. However, challenges such as tumor hypoxia, limited tissue penetration and phototoxicity necessitate ongoing research efforts to optimize PDT protocols and overcome limitations. Overall, PDT is versatile and continually advancing with refined protocols to improve its clinical utility against cancer and microbial infections., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This research was carried out to predict daily streamflow for the Swat River Basin, Pakistan through four deep learning (DL) models: Feed Forward Artificial Neural Networks (FFANN), Seasonal Artificial Neural Networks (SANN), Time Lag Artificial Neural Networks (TLANN) and Long Short-Term Memory (LSTM) under two Shared Socioeconomic Pathways (SSPs) 585 and 245. Taylor Diagram, Random Forest, and Gradient Boosting techniques were used to select the best combination of General Circulation Models (GCMs) for Multi-Model Ensemble (MME) computation. MME was computed via the Random Forest technique for Maximum Temperature (T max ), Minimum Temperature (T min ), and precipitation for the aforementioned three techniques. The best MME for T max , T min , and precipitation was rendered by Compromise Programming. The DL models were trained and tested using observed precipitation and temperature as independent variables and discharge as dependent variables. The results of deep learning models were evaluated using statistical performance indicators such as root mean square error (RMSE), mean square error (MSE), mean absolute error (MAE), and coefficient of determination (R 2 ). The TLANN demonstrated superior performance compared to the other models based on RMSE, MSE, MAE, and R 2 during training (65.25 m 3 /s, 4256.97 m 3 /s, 46.793 m 3 /s and 0.7978) and testing (72.06 m 3 /s, 5192.95 m 3 /s, 51.363 m 3 /s and 0.7443) respectively. Subsequently, TLANN was utilized to make predictions based on MME of SSP245 and SSP585 scenarios for future streamflow until the year 2100. These results can be used for planning, management, and policy-making regarding water resources projects in the study area., (© 2024. The Author(s).)

With the rapid development of micro/nano machining, there is an elevated demand for high-performance microdevices with high reliability and low cost. Due to their outstanding electrochemical, optical, electrical, and mechanical performance, carbon materials are extensively utilized in constructing microdevices for energy storage, sensing, and optoelectronics. Carbon micro/nano machining is fundamental in carbon-based intelligent microelectronics, multifunctional integrated microsystems, high-reliability portable/wearable consumer electronics, and portable medical diagnostic systems. Despite numerous reviews on carbon materials, a comprehensive overview is lacking that systematically encapsulates the development of high-performance microdevices based on carbon micro/nano structures, from structural design to manufacturing strategies and specific applications. This review focuses on the latest progress in carbon micro/nano machining toward miniaturized device, including structural engineering, large-scale fabrication, and performance optimization. Especially, the review targets an in-depth evaluation of carbon-based micro energy storage devices, microsensors, microactuators, miniaturized photoresponsive and electromagnetic interference shielding devices. Moreover, it highlights the challenges and opportunities in the large-scale manufacturing of carbon-based microdevices, aiming to spark further exciting research directions and application prospectives., (© 2024 Wiley‐VCH GmbH.)

The study aims at assessing the potential of graphene-based adsorbents to reduce environmental impacts of Iodinated Contrast Media Agents (ICMs). We analyze an extensive collection of ICMs. A modeling approach resting on molecular docking and Density Functional Theory simulations is employed to examine the adsorption process at the molecular level. The study also relies on a Quantitative Structure-Activity Relationship (QSAR) modeling framework to correlate molecular properties with the adsorption energy (E ad ) of ICMs, thus enabling identification of the key mechanisms underpinning adsorption and of the key factors contributing to it. A collection of distinct QSAR-based models is developed upon relying on Multiple Linear Regression and a standard genetic algorithm method. Having at our disposal multiple models enables us to take into account the uncertainty associated with model formulation. Maximum Likelihood and formal model identification/discrimination criteria (such as Bayesian and/or information theoretic criteria) are then employed to complement the traditional QSAR modeling phase. This has the advantage of (a) providing a rigorous ranking of the alternative models included in the selected set and (b) quantifying the relative degree of likelihood of each of these models through a weight or posterior probability. The resulting workflow of analysis enables one to seamlessly embed DFT and QSAR studies within a theoretical framework of analysis that explicitly takes into account model and parameter uncertainty. Our results suggest that graphene-based surfaces constitute a promising adsorbent for ICMs removal, π-π stacking being the primary mechanism behind ICM adsorption. Furthermore, our findings offer valuable insights into the potential of graphene-based adsorbent materials for effectively removing ICMs from water systems. They contribute to ascertain the significance of various factors (such as, e.g., the distribution of atomic van der Waals volumes, overall molecular complexity, the presence and arrangement of Iodine atoms, and the presence of polar functional groups) on the adsorption process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology., Methods: This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein., Key Findings: In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats., Conclusion: Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study reports a novel CuSe-TiO 2 -GO composite, synthesized by a facile hydrothermal method at a controlled temperature, and investigates its electrochemical performance for supercapacitors (SCs) and photocatalytic behavior for degrading methylene blue (MB) dye. The compositional phase structure and chemical bond interaction were thoroughly investigated. The as-fabricated pristine, binary, and ternary composites underwent comprehensive characterization employing spectroscopic techniques and electrochemical analysis. Compared with pure and binary compounds (CuSe, TiO 2 , and binary CuSe-TiO 2 composites), the ternary CuSe-TiO 2 -GO composites demonstrated a high degradation efficiency while degrading MB in less than just 80 min (240 min, 100 min, and 140 min, respectively). The photocatalytic activity of the ternary CuSe-TiO 2 -GO composites is enhanced due to the highly positive conduction band of CuSe, leading to the quick excitation of electrons to the conduction band of CuSe. Subsequently, graphene oxide (GO) left holes on the photocatalyst surface for MB, as GO assisted the photoexcited electron-hole pairs, resulting in enhanced photocatalytic performance. The CuSe-TiO 2 -GO electrode for the supercapacitor indicates a 310.6 F/g and 135.2 F/g capacitance when the discharge current upsurges from 1 to 12 A/g. The good photocatalytic and energy storage performance is due to the smaller charge transfer resistance, which promotes efficient separation of electron-hole pairs.

Purpose: Although plastic scintillator detectors (PSDs) are considered ideal dosimeters for small field dosimetry in conventional linear accelerators (linacs), the impact of the magnetic field strength on the response of the PSD must be investigated., Methods: A linac Monte Carlo (MC) head model for a low-field MR-linac was validated for small field dosimetry and utilized to calculate field output factors (OFs). The MC-calculated OFs were compared with the treatment planning system (TPS)-calculated OFs and measured OFs using a Blue Physics (BP) Model 10 commercial PSD and a synthetic diamond detector. The field-specific correction factors, [Formula: see text] , were calculated for the PSD in the presence of a 0.35 T and magnetic field. The impact of the source focal spot size and initial electron energy on the MC-calculated OFs was investigated., Results: Good agreement to within 2 % was found between the MC-calculated OFs and BP PSD OFs except for the 0.415 × 0.415 cm 2 field size. The BP PSD [Formula: see text] correction factors were calculated to be within 1 % of unity. For field sizes ≥1.66 × 1.66 cm 2 , the MC-calculated OFs were relatively insensitive to the focal spot size and initial electron energy to within 2.5 %. However, for smaller field sizes, the MC-calculated OFs were found to differ up to 9.50 % and 7.00 % when the focal spot size and initial electron energy was varied, respectively., Conclusions: The BP PSD was deemed suitable for small field dosimetry in MR-linacs without requiring any [Formula: see text] correction factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Aim: Head and Neck squamous cell carcinoma (HNSCC) is the second most prevalent cancer in Pakistan. Methods: Gene expression data from TCGA and GETx for normal genes to analyze Differentially Expressed Genes (DEGs). Data was further investigated using the Enrichr tool to perform Gene Ontology (GO). Results: Our analysis identified most significantly differentially expressed genes and explored their established cellular functions as well as their potential involvement in tumor development. We found that the highly expressed Keratin family and S100A9 genes. The under-expressed genes KRT4 and KRT13 provide instructions for the production of keratin proteins. Conclusion: Our study suggests that factors such as poor oral hygiene and smokeless tobacco can result in oral stress and cellular damage and cause cancer.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease., Methods: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018., Results: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages., Conclusion: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Seizures are a common sequela for patients suffering from gliomas. Molecular properties are known to influence the initiation of seizures that may influence tumor growth. Different levels of gene expression with seizures related to gliomas remain unclear. We analyzed RNA sequencing of gliomas to further probe these differences., Methods: Total RNA sequencing was obtained from The Cancer Genome Atlas-Lower-Grade Glioma project, comprised of 2021 World Health Organization classification low-grade gliomas, including IDH-mutant and IDH-wild type, to distinguish differential expression in patients who did and did not experience seizures. Utilizing QIAGEN Ingenuity Pathways Analysis, we identified canonical and functional pathways to characterize differential expression., Results: Of 289 patients with gliomas, 83 (28.7%) had available information regarding seizure occurrence prior to intervention and other pertinent variables of interest. Of these, 50 (60.2%) were allocated to the seizure group. When comparing the level of RNA expression from these tumors between the seizure and non-seizure groups, 52 genes that were significantly differentially regulated were identified. We found canonical pathways that were altered, most significantly RhoGDI and semaphorin neuronal repulsive signaling. Functional gene analysis revealed tumors that promoted seizures had significantly increased functional gene sets involving neuronal differentiation and synaptogenesis., Conclusions: In the setting of gliomas, differences in tumor gene expression exist between individuals with and without seizures, despite similarities in patient demographics and other tumor characteristics. There are significant differences in gene expression associated with neuron development and synaptogenesis, ultimately suggesting a mechanistic role of a tumor-neuron synapse in seizure initiation., Competing Interests: No conflict of interest., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology 2024.)

Peste des petits ruminants (PPR) is an extremely transmissible viral disease caused by the PPR virus that impacts domestic small ruminants, namely sheep and goats. This study aimed to employ a methodical approach to evaluate the regional occurrence of PPR in small ruminants in Pakistan and the contributing factors that influence its prevalence. A thorough search was performed in various databases to identify published research articles between January 2004 and August 2023 on PPR in small ruminants in Pakistan. Articles were chosen based on specific inclusion and exclusion criteria. A total of 25 articles were selected from 1275 studies gathered from different databases. The overall pooled prevalence in Pakistan was calculated to be 51% (95% CI: 42-60), with heterogeneity I 2 = 100%, τ 2 = 0.0495, and p = 0. The data were summarized based on the division into five regions: Punjab, Baluchistan, KPK, Sindh, and GB and AJK. Among these, the pooled prevalence of PPR in Sindh was 61% (95% CI: 46-75), I 2 = 100%, τ 2 = 0.0485, and p = 0, while in KPK, it was 44% (95% CI: 26-63), I 2 = 99%, τ 2 = 0.0506, and p < 0.01. However, the prevalence of PPR in Baluchistan and Punjab was almost the same. Raising awareness, proper surveillance, and application of appropriate quarantine measures interprovincially and across borders must be maintained to contain the disease.

The present study explored the nutritional composition, phytochemicals analysis, and antioxidant capacity of two indigenous varieties of red and green water chestnut (WCN) fruit grown in Pakistan. Accordingly, this study was designed to investigate the proximate composition (moisture, ash, fiber, proteins, fat, and energy), physicochemical properties (pH, °Brix, and glycemic index), minerals, and vitamins. The methanolic extracts of WCN fruits were explored for phytochemicals (total phenolic and flavonoid content), and antioxidant potential was examined in vitro by 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity (DPPH) and Ferric reducing antioxidant power (FRAP). Quantitative determination of mineral (sodium, potassium, calcium, phosphorus, iron, manganese, copper, and zinc) and vitamin (vitamin C, vitamin B6, vitamin B2, vitamin B3, vitamin A, and β -Carotene) composition was also assessed. Based on the findings, the proximate compositions of WCN green and red varieties varied greatly as WCN green contained significantly higher protein (1.72%), fat (0.65%), dietary fiber (2.21%), moisture (70.23%), ash (1.16%), and energy content (112.8 Kcal) than WCN red. In WCN green, the macro-micromineral concentrations were significantly higher than WCN red. Among the minerals analyzed, potassium was the most abundant mineral found in both varieties. Levels of vitamin C, B 6 , A, and β -Carotene were significantly higher in WCN green. In this study, methanolic extract showed higher extraction efficiency than acetone, ethanol, and distilled water. WCN green had a significantly higher quantum of total phenolic (91.13 mg GAE/g) and total flavonoid (36.6 mg QE/g) and presented significantly higher antioxidant activity than the WCN red. This study showed that, among both varieties, WCN green extract has therapeutic potential against free radical mediated health conditions and suggested the potential use of this fruit as a source of natural antioxidants in nutraceuticals.

Metal-oxide-based gas sensors are extensively utilized across various domains due to their cost-effectiveness, facile fabrication, and compatibility with microelectronic technologies. The copper (Cu)-based multifunctional polymer-enhanced sensor (CuMPES) represents a notably tailored design for non-invasive environmental monitoring, particularly for detecting diverse gases with a low concentration. In this investigation, the Cu-CuO/PEDOT nanocomposite was synthesized via a straightforward chemical oxidation and vapor-phase polymerization. Comprehensive characterizations employing X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro Raman elucidated the composition, morphology, and crystal structure of this nanocomposite. Gas-sensing assessments of this CuMPES based on Cu-CuO/PEDOT revealed that the response current of the microneedle-type CuMPES surpassed that of the pure Cu microsensor by nearly threefold. The electrical conductivity and surface reactivity are enhanced by poly (3,4-ethylenedioxythiophene) (PEDOT) polymerized on the CuO-coated surface, resulting in an enhanced sensor performance with an ultra-fast response/recovery of 0.3/0.5 s.

With the increasing population worldwide more wastewater is created by human activities and discharged into the waterbodies. This is causing the contamination of aquatic bodies, thus disturbing the marine ecosystems. The rising population is also posing a challenge to meet the demands of fresh drinking water in the water-scarce regions of the world, where drinking water is made available to people by desalination process. The fouling of composite membranes remains a major challenge in water desalination. In this innovative study, we present a novel probabilistic approach to analyse and anticipate the predominant fouling mechanisms in the filtration process. Our establishment of a robust theoretical framework hinges upon the utilization of both the geometric law and the Hermia model, elucidating the concept of resistance in series (RIS). By manipulating the transmembrane pressure, we demonstrate effective management of permeate flux rate and overall product quality. Our investigations reveal a decrease in permeate flux in three distinct phases over time, with the final stage marked by a significant reduction due to the accumulation of a denser cake layer. Additionally, an increase in transmembrane pressure leads to a correlative rise in permeate flux, while also exerting negative effects such as membrane ruptures. Our study highlights the minimal immediate impact of the intermediate blocking mechanism (n = 1) on permeate flux, necessitating continuous monitoring for potential long-term effects. Additionally, we note a reduced membrane selectivity across all three fouling types (n = 0, n = 1.5, n = 2). Ultimately, our findings indicate that the membrane undergoes complete fouling with a probability of P = 0.9 in the presence of all three fouling mechanisms. This situation renders the membrane unable to produce water at its previous flow rate, resulting in a significant reduction in the desalination plant's productivity. I have demonstrated that higher pressure values notably correlate with increased permeate flux across all four membrane types. This correlation highlights the significant role of TMP in enhancing the production rate of purified water or desired substances through membrane filtration systems. Our innovative approach opens new perspectives for water desalination management and optimization, providing crucial insights into fouling mechanisms and proposing potential strategies to address associated challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel., Methods: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed., Results: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery., Conclusion: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Backgound: Alzheimer disease (AD) is a disastrous disease characterized by accretion of amyloid-beta plaques, neurofibrillary tangles inducing oxidative stress, loss of neuronal functions and continuous progression of cognitive impairment leading to severe dementia., Material and Methods: The newly synthesized benzimidazole derivative 4-chloro-3-(2-phenyl-1H-benzimidazole-1-sulfonyl) benzoic acid (CB) was evaluated for its anti-Alzheimer activity using in silico , in vivo , in vitro and molecular techniques (ELISA, WB & IHC) ., Results: In-silico studies revealed that CB has atomic contact energy values of -3.9 to -8.9 kcal/mol against selected targets. In vitro assay showed that CB caused acetylcholinesterase (AChE) and diphenyl-1-picrylhydrazyl inhibition. In-vivo findings revealed improvement in dementia as observed in the morris water maze test and Ymaze test. Amyloid-beta disaggregation, increased level of anti-oxidants, decreased expressions of inflammatory markers and enhanced cellular architecture were found in the cortex and hippocampus of treated rats in the histopathological examination, immunohistochemistry analysis, enzyme-linked immunosorbent assay and western blot analysis., Conclusions: This study revealed that CB possess different binding affinities with the Alzheimer-related targets and it possess anti-Alzheimer activity, mediated via AChE and amyloid-beta inhibition, anti-oxidant and anti-inflammatory pathways.

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Larry A. DeWerd reports a relationship with Standard Imaging Inc that includes: board membership and equity or stocks. Co-author is an editor for Applied Radiation and Isotopes - W.C. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antimicrobial resistance is an emerging threat to public health around the world. The study employs computational and biophysical methods to investigate the properties of cefotaxime and meropenem's binding to various beta-lactamases like TEM-1, SHV-1, KPC-2, and Amp-C. The enzyme kinetics of purified proteins revealed an increase in Michaelis constant (K m ) value in the presence of meropenem and cefotaxime, indicating a decrease in enzyme affinity for nitrocefin. Proteins interact with meropenem/cefotaxime, causing quenching through complex formation. All proteins have one binding site, and binding constant (K b ) values are 10 4 , indicating strong interaction. The study found that meropenem and cefotaxime had high fitness scores for Amp-C, KPC-2,TEM-1 and SHV-1, with binding energy ranging from -7.4 to -7.8, and hydrogen bonds between them. Molecular Dynamic simulation of protein-ligand complexes revealed cefotaxime-binding proteins have slightly lower Root Mean Square Deviation(RMSD) than meropenem-binding proteins, indicating stable association antibiotics with these proteins., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To compare the safety and efficacy of the Preserflo Microshunt with trabeculectomy in the treatment of patients with glaucoma. A systematic review and meta-analysis was conducted. The primary outcome measures recorded as a measure of efficacy of the interventions were intra-ocular pressure (IOP) at final follow-up and IOP reduction (IOPR). Secondary outcomes recorded to measure efficacy were reduction in the number of glaucoma medications and reinterventions. To assess safety profile, the proportions of patients with post-operative complications were recorded. Seven articles were included in this study. A total of 1353 eyes were included in this review (Preserflo: 812, trabeculectomy: 541). Post-operative IOP (mean difference [MD] = 0.78 [0.66, 0.90], p < 0.001) results are significantly lower for trabeculectomy than Preserflo. The IOPR (MD = -1.20 [-2.30, -0.09], p = 0.034) results significantly favour trabeculectomy over Preserflo Microshunt. The reduction in topical glaucoma medications (MD = -0.32 [-0.58, -0.07], p = 0.014) is significantly higher for trabeculectomy. There is no statistically significant difference in levels of hypotony (risk ratio [RR] = -0.05 [-0.47, 0.37], p = 0.806), choroidal effusion/detachment (RR = -0.12 [-0.42, 0.19], p = 0.444), hyphaema (RR = 0.20 [-0.11, 0.51], p = 0.216) and flat anterior chamber (RR = 0.49 [-1.02, 0.03], p = 0.066). There are significantly more bleb-related complications in the trabeculectomy groups than Preserflo groups (RR = -0.63 [-1.01, -0.24], p = 0.001). There were statistically more reinterventions required in the trabeculectomy groups than Preserflo groups (RR = -0.48 [-0.65, -0.30], p < 0.001). Compared to trabeculectomy, the Preserflo Microshunt is not as effective in lowering intra-ocular pressure, has a similar safety profile and has a lower reintervention rate. Further research is required given the lack of randomised controlled trials within this study and resulting low strength of evidence., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Small-field dosimetry used in special procedures such as gamma knife, Cyberknife, Tomotherapy, IMRT, and VMAT has been in evolution after several radiation incidences with very significant (70%) errors due to poor understanding of the dosimetry. IAEA-TRS-483 and AAPM-TG-155 have provided comprehensive information on small-fields dosimetry in terms of code of practice and relative dosimetry. Data for various detectors and conditions have been elaborated. It turns out that with a suitable detectors dose measurement accuracy can be reasonably (±3%) achieved for 6 MV beams for fields >1×1 cm2. For grid therapy, even though the treatment is performed with small fields created by either customized blocks, multileaf collimator (MLC), or specialized devices, it is multiple small fields that creates combined treatment. Hence understanding the dosimetry in collection of holes of small field is a separate challenge that needs to be addressed. It is more critical to understand the scattering conditions from multiple holes that form the treatment grid fields. Scattering changes the beam energy (softer) and hence dosimetry protocol needs to be properly examined for having suitable dosimetric parameters. In lieu of beam parameter unavailability in physical grid devices, MLC-based forward and inverse planning is an alternative path for bulky tumours. Selection of detectors in small field measurement is critical and it is more critical in mixed beams created by scattering condition. Ramification of small field concept used in grid therapy along with major consideration of scattering condition is explored. Even though this review article is focussed mainly for dosimetry for low-energy megavoltage photon beam (6 MV) but similar procedures could be adopted for high energy beams. To eliminate small field issues, lattice therapy with the help of MLC is a preferrable choice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pruritus, or itching, is a distressing symptom associated with various dermatological and systemic diseases. L-carnitine (βeta hydroxy-γ-tri methyl amino-butyric acid), is a naturally occurring substance, it controls numerous physiological processes. The present research aims to identify L-carnitine for its anti-pruritic effect via nitric oxide-dependent mechanism., Methods: Chloroquine-induced pruritus serves as an experimental model to investigate possible therapeutic interventions. In this study, we evaluated the efficacy of L-carnitine in combating oxidative stress, nitric oxide, and inflammatory cytokines in a chloroquine-induced pruritus model., Results: L-carnitine treatment significantly reduced scratching behavior compared to the disease group ( *** P < 0.001 vs. chloroquine group), indicating its antipruritic potential. The markers of oxidative stress, GST, GSH, Catalase, and LPO were dysregulated in the disease model, but administration of L-carnitine restored GST, GSH, and Catalase levels and decreased LPO levels ( *** P < 0.001 vs. chloroquine group), thereby alleviating oxidative stress. L-carnitine also reduced nitric oxide synthase (NOS) activity, suggesting that it modulates nitric oxide signaling pathways involved in pruritus. In addition, L-carnitine lowered levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), inflammatory marker nuclear factor kappa B (p-NFκB) and also reduces an inflammatory enzyme, cyclooxygenase-2 (COX-2), determined by ELISA (Enzyme-Linked Immunosorbent Assay) ( *** P < 0.001 vs. chloroquine group). It downregulates nNOS mRNA expression confirmed by real-time polymerase chain reaction (RT-PCR)., Conclusion: These findings highlight the therapeutic effects of L-carnitine in alleviating chloroquine-induced pruritus., (© 2024. The Author(s).)

Background: Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT)., Results: This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 μg/mL), while broth microdilution identified 48 (MIC = 32-128 μg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated bla NDM-5 (K. pneumoniae ST147) and chromosomally mediated bla NDM-1 (P. aeruginosa ST357)., Conclusion: The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance., (© 2024. The Author(s).)

Background: Diffusing alpha-emitters radiation therapy (DaRT) is a novel brachytherapy technique that leverages the diffusive flow of 224 Ra progeny within the tumor volume over the course of the treatment. Cell killing is achieved by the emitted alpha particles that have a short range in tissue and high linear energy transfer. The current proposed absorbed dose calculation method for DaRT is based on a diffusion-leakage (DL) model that neglects absorbed dose from beta particles., Purpose: This work aimed to couple the DL model with dose point kernels (DPKs) to account for dose from beta particles as well as to consider the non-local deposition of energy., Methods: The DaRT seed was modeled using COMSOL multiphysics and the DL model was implemented to extract the spatial information of the diffusing daughters. Using Monte-Carlo (MC) methods, DPKs were generated for 212 Pb, 212 Bi, and their progenies since they were considered to be the dominant beta emitters in the 224 Ra radioactive decay chain. A convolution operation was performed between the integrated number densities of the diffusing daughters and DPKs to calculate the total absorbed dose over a 30-day treatment period. Both high-diffusion and low-diffusion cases were considered., Results: The calculated DPKs showed non-negligible energy deposition over several millimeters from the source location. An absorbed dose >10 Gy was deposited within a 1.8 mm radial distance for the low diffusion case and a 2.2 mm radial distance for the high diffusion case. When the DPK method was compared with the local energy deposition method that solely considered dose from alpha particles, differences above 1 Gy were found within 1.3 and 1.8 mm radial distances from the surface of the source for the low diffusion and high diffusion cases, respectively., Conclusions: The proposed method enhances the accuracy of the dose calculation method used for the DaRT technique., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

This study attempts to identify factors that significantly encourage the cessation of smoking in the context of Pakistan. The study distributes a modified questionnaire among 421 respondents (current as well as former smokers) in the capital city of Pakistan, Islamabad. The binary regression method was employed to data for analyzing predictors of making quit attempts and successful smoking cessation. The result indicates that respondents having strong intentions to quit, high socioeconomic status, low nicotine dependency, and past quit attempts, and those having no-smoking friends, are more likely to quit cigarette smoking successfully. On the other hand, factors like social pressure to quit smoking, religious information against smoking, intention to quit smoking, and public regulation on smoking are more likely to encourage smokers to make quit attempts. The study calls for community and school-wide smoking cessation campaigns involving officials, peers and parents, religious leaders, and other influential individuals to inform people about the dangers of smoking. In addition, religious leaders should be encouraged to issue rulings against smoking especially during "Friday Prayer." Furthermore, the government should pronounce more strict and comprehensive regulations on smoking by properly monitoring its implementation to encourage cessation of cigarette smoking., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The current study aimed to investigate the influence of taxifolin on depression symptoms alleviation in Male Sprague-Dawley rats by targeting underlying pathways of depression. Molecular docking analyses were conducted to validate taxifolin's binding affinities against various targets. In silico analysis of taxifolin revealed various aspects of post docking interactions with different protein targets. Depression was induced in rats via intraperitoneal injection of Lipopolysaccharide (LPS; 500 μ g/Kg) for 14 alternative days. Rats (n = 6/group) were randomly assigned to four groups: (i) Saline/Control, (ii) Disease (LPS 500 μg/kg), (iii) Standard (fluoxetine 20 mg/kg), and (iv) Treatment (taxifolin 20 mg/kg). At the end of the in vivo study, brain samples were used for biochemical and morphological analysis. Taxifolin exhibited neuroprotective effects, as evidenced by behavioral studies, antioxidant analysis, histopathological examination, immunohistochemistry, ELISA and RT PCR, indicating an increase number of surviving neurons, normalization of cell size and shape, and reduction in vacuolization. Taxifolin also decreased inflammatory markers such as TNF-α, NF-κb, IL-6 and COX-2, while significantly upregulating and activating the protective PPAR-γ pathway, through which it reduces the oxidative stress, neuroinflammation, neurodegeneration, thereby ameliorating depression symptoms in experimental rat model of depression. Our finding suggests that taxifolin act as neuroprotective agent partially mediated through PPAR-γ pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The use of single-walled carbon nanotubes (SWCNTs) in biomedical applications is limited due to their inability to disperse in aqueous solutions. In this study, dispersed -COOH functionalized CNTs with N-succinylated chitosan (CS), greatly increasing the water solubility of CNTs and forming a uniformly dispersed nanocomposite solution of CNTs@CS. Coupling reagent EDC/NHS was used as a linker with the -COOH groups present on the N-succinylated chitosan which significantly improved the affinity of the CNTs for biomolecules. Myoglobin (Mb) is a promising biomarker for the precise assessment of cardiovascular risk, type 2 diabetes, metabolic syndrome, hypertension and several types of cancer. A high level of Mb can be used to diagnose the mentioned pathogenic diseases. The CNTs@CS-FET demonstrates superior sensing performance for Mb antigen fortified in buffer, with a wide linear range of 1 to 4000 ng/mL. The detection limit of the developed Mb immunosensor was estimated to be 4.2 ng/mL. The novel CNTs@CS-FET immunosensor demonstrates remarkable capability in detecting Mb without being affected by interferences from nonspecific antigens. Mb spiked serum showed a recovery rate of 100.262 to 118.55 % indicating great promise for Mb detection in clinical samples. The experimental results confirmed that the CNTs@CS-FET immunosensor had excellent selectivity, reproducibility and storage stability., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

MCM7 (Minichromosome Maintenance Complex Component 7) is a component of the DNA replication licensing factor, which controls DNA replication. The MCM7 protein is linked to tumor cell proliferation and has a function in the development of several human cancers. Several types of cancer may be treated by inhibiting the protein, as it is strongly produced throughout this process. Significantly, Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant use against cancer, is rapidly gaining traction as a valuable medical resource for the development of novel cancer therapies, including immunotherapy. Therefore, the goal of the research was to find small molecular therapeutic candidates against the MCM7 protein that may be used to treat human cancers. A computational-based virtual screening of 36,000 natural TCM libraries is carried out for this goal using a molecular docking and dynamic simulation technique. Thereby, ∼8 novel potent compounds i.e., ZINC85542762, ZINC95911541, ZINC85542617, ZINC85542646, ZINC85592446, ZINC85568676, ZINC85531303, and ZINC95914464 were successfully shortlisted, each having the capacity to penetrate the cell as potent inhibitors for MCM7 to curb this disorder. These selected compounds were found to have high binding affinities compared to the reference (AGS compound) i.e. < -11.0 kcal/mol. ADMET and pharmacological properties showed that none of these 8 compounds poses any toxic property (carcinogenicity) and have anti-metastatic, and anticancer activity. Additionally, MD simulations were run to assess the compounds' stability and dynamic behavior with the MCM7 complex for about 100 ns. Finally, ZINC95914464, ZINC95911541, ZINC85568676, ZINC85592446, ZINC85531303, and ZINC85542646 are identified as highly stable within the complex throughout the 100 ns simulations. Moreover, the results of binding free energy suggested that the selected virtual hits significantly bind to the MCM7 which implied these compounds may act as a potential MCM7 inhibitor. However, in vitro testing protocols are required to further support these results. Further, assessment through various lab-based trial methods can assist with deciding the action of the compound that will give options in contrast to human cancer immunotherapy.Communicated by Ramaswamy H. Sarma.

Industrialization and population growth are leading to the production of significant amounts of sewage containing hazardous xenobiotic compounds. These compounds pose a threat to human and animal health, as well as the overall ecosystem. To combat this issue, chemical, physical, and biological techniques have been used to remove these contaminants from water bodies affected by human activity. Biotechnological methods have proven effective in utilizing microorganisms and enzymes, particularly laccases, to address this problem. Laccases possess versatile enzymatic characteristics and have shown promise in degrading different xenobiotic compounds found in municipal, industrial, and medical wastewater. Both free enzymes and crude enzyme extracts have demonstrated success in the biotransformation of these compounds. Despite these advancements, the widespread use of laccases for bioremediation and wastewater treatment faces challenges due to the complex composition, high salt concentration, and extreme pH often present in contaminated media. These factors negatively impact protein stability, recovery, and recycling processes, hindering their large-scale application. These issues can be addressed by focusing on large-scale production, resolving operation problems, and utilizing cutting-edge genetic and protein engineering techniques. Additionally, finding novel sources of laccases, understanding their biochemical properties, enhancing their catalytic activity and thermostability, and improving their production processes are crucial steps towards overcoming these limitations. By doing so, enzyme-based biological degradation processes can be improved, resulting in more efficient removal of xenobiotics from water systems. This review summarizes the latest research on bacterial laccases over the past decade. It covers the advancements in identifying their structures, characterizing their biochemical properties, exploring their modes of action, and discovering their potential applications in the biotransformation and bioremediation of xenobiotic pollutants commonly present in water sources., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The current study report a convenient, simple, and low cost approach for the biogenic synthesis of CuO/Fe 3 O 4 nanocomposites (NCs) from pumpkin seeds extract and their vitro cytotoxicity. The characterization of finally obtained CuO/Fe 3 O 4 nanocomposites (NCs) performed using UV-Visible, FT-IR, XRD, XPS, GC-MS, SEM-EDX and TEM analysis. The formation and elemental analysis were determined using the energy-dispersive X-ray (EDX) microanalysis technique. The formation of rod-like monoclinic and spherical, having size range 5 nm-20 nm confirmed by scanning electron microscope (SEM) and transmission electron microscopy (TEM) respectively. Finally, the MTT assay of the synthesized composites was evaluated for toxicity against cancerous cell lines HCT-116 (Colon cancer cell) and A549 (human lung adenocarcinoma cell). The synthesized composite material showed moderate (IC 50  = 199 μg/mL) to low (IC 50  = 445 μg/mL) activity against HCT-116 and A549 cell lines, respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study aimed to investigate the characterization of zinc oxide nanoparticles (ZnONPs) produced from Cucurbita pepo L. (pumpkin seeds) and their selective cytotoxic effectiveness on human colon cancer cells (HCT 116) and African Green Monkey Kidney, Vero cells. The study also investigated the antioxidant activity of ZnONPs. The study also examined ZnONPs' antioxidant properties. This was motivated by the limited research on the comparative cytotoxic effects of ZnO NPs on normal and HCT116 cells. The ZnO NPs were characterized using Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Transmission Electron Microscope/Selected Area Electron Diffraction (TEM/SAED), and Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX) for determination of chemical fingerprinting, heat stability, size, and morphology of the elements, respectively. Based on the results, ZnO NPs from pumpkins were found to be less than 5 μm and agglomerates in nature. Furthermore, the ZnO NPs fingerprinting and SEM-EDX element analysis were similar to previous literature, suggesting the sample was proven as ZnO NPs. The ZnO NPs also stable at a temperature of 380°C indicating that the green material is quite robust at 60-400°C. The cell viability of Vero cells and HCT 116 cell line were measured at two different time points (24 and 48 h) to assess the cytotoxicity effects of ZnO NP on these cells using AlamarBlue assay. Cytotoxic results have shown that ZnO NPs did not inhibit Vero cells but were slightly toxic to cancer cells, with a dose-response curve IC50 = ~409.7 μg/mL. This green synthesis of ZnO NPs was found to be non-toxic to normal cells but has a slight cytotoxicity effect on HCT 116 cells. A theoretical study used molecular docking to investigate nanoparticle interaction with cyclin-dependent kinase 2 (CDK2), exploring its mechanism in inhibiting CDK2's role in cancer. Further study should be carried out to determine suitable concentrations for cytotoxicity studies. Additionally, DPPH has a significant antioxidant capacity, with an IC50 of 142.857 μg/mL. RESEARCH HIGHLIGHTS: Pumpkin seed extracts facilitated a rapid, high-yielding, and environmentally friendly synthesis of ZnO nanoparticles. Spectrophotometric analysis was used to investigate the optical properties, scalability, size, shape, dispersity, and stability of ZnO NPs. The cytotoxicity of ZnO NPs on Vero and HCT 116 cells was assessed, showing no inhibition of Vero cells and cytotoxicity of cancer cells. The DPPH assay was also used to investigate the antioxidant potential of biogenic nanoparticles. A molecular docking study was performed to investigate the interaction of ZnO NPs with CDK2 and to explore the mechanism by which they inhibit CDK2's role in cancer., (© 2023 Wiley Periodicals LLC.)

Heart failure is a condition in which the heart's one or both ventricles are unable to either receive an adequate amount of blood or eject an adequate amount of blood. Diabetes is considered one of the major risk factors for cardiovascular diseases. The current research is designed to evaluate the cardioprotective effects of dapagliflozin in streptozotocin and isoproterenol-induced comorbid rats. The COX-2, TNF-α, NF-КB, NLRP3, PPAR-γ, CKMB, TROP-I, AR, GP and SGLT were docked against dapagliflozin, propranolol and metformin. Dapagliflozin restored adequate blood flow and halted myofibril damage. Moreover, it's evident from this study that dapagliflozin significantly decreased serum concentration of various blood markers, decreased relative growth rate and QT interval prolongation, as compared to the negative control group. However, it improved the ventricular ejection fraction in rats of the treatment group. The GST, GSH and CAT levels were increased, as compared to normal. On the contrary, a decrease in LPO concentrations was observed. Evaluation of the coronal section of heart tissues showed the anti-inflammatory expressions evaluated through H & E staining and immunohistochemical techniques and with ELISA and PCR. In a nutshell, dapagliflozin reverses myocardial necrosis and apoptosis.

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Yang, Zhang, Khan, Dai and Ouyang.)