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The intersection of mathematical modeling, nanotechnology, and epidemiology marks a paradigm shift in our battle against infectious diseases, aligning with the focus of the journal on the regulation, expression, function, and evolution of genes in diverse biological contexts. This exploration navigates the intricate dance of viral transmission dynamics, highlighting mathematical models as dual tools of insight and precision instruments, a theme relevant to the diverse sections of Gene. In the context of virology, ethical considerations loom large, necessitating robust frameworks to protect individual rights, an aspect essential in infectious disease research. Global collaboration emerges as a critical pillar in our response to emerging infectious diseases, fortified by the predictive prowess of mathematical models enriched by nanotechnology. The synergy of interdisciplinary collaboration, training the next generation to bridge mathematical rigor, biology, and epidemiology, promises accelerated discoveries and robust models that account for real-world complexities, fostering innovation and exploration in the field. In this intricate review, mathematical modeling in viral transmission dynamics and epidemiology serves as a guiding beacon, illuminating the path toward precision interventions, global preparedness, and the collective endeavor to safeguard human health, resonating with the aim of advancing knowledge in gene regulation and expression., 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. Published by Elsevier B.V.)

Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Mental health in people with epilepsy (PWE) is often overlooked, especially in developing countries. Purpose: Consequently, the current work had two objectives: (1) to estimate the burden of depression, anxiety, insomnia, and stress, and (2) to examine the association of these psychiatric/psychological symptoms with levetiracetam and other relevant clinical factors in a cohort of Jordanian PWE. Research Design: This is a cross-sectional study. The demographic and clinical data were recorded. Depression was measured by the Patient Health Questionnaire-9 (PHQ-9, Arabic-validated version) and anxiety by the General Anxiety Disorder-7 (GAD-7, Arabic-validated version). The insomnia severity index (ISI-A, Arabic version) was used to assess sleep quality, and the Perceived Stress Scale (PSS-A, Arabic version) was used to measure perceived stress. Study Sample: Data were analyzed from 280 patients, of which 178 (63.6%) received levetiracetam as monotherapy or as adjuvant. Results: Depression was reported in 150 (53.6%), anxiety in 110 (39.3%), insomnia in 131 (46.8%), and clinically significant stress in 211 (75.4%). At univariate analysis, levetiracetam was not associated with psychiatric symptoms. Multivariate logistic regression revealed that severe depressive symptoms were associated with family history (OR = 2.47, 95% CI = 1.42-4.33, P = .001) and seizure type (OR = 1.69, 95% CI = 1.01-2.80, P = .04), severe anxiety symptoms were associated with family history (OR = 1.90, 95% CI = 1.12-3.23, P = .01), severe insomnia was associated with seizure type (OR = 2.16, 95% CI = 1.33-3.5, P = .002) and severe stress was associated with marital status (OR = 2.37, 95% CI = 1.31-4.29, P = .004). Conclusions: The high psychological burden of PWE is a challenging issue that requires attention and prompt action to control its risk factors. Levetiracetam was not associated with psychiatric symptoms in this study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The growing requirement for real-time monitoring of health factors such as heart rate, temperature, and blood glucose levels has resulted in an increase in demand for electrochemical sensors. This study focuses on enzyme-free glucose sensors based on 2D-MoS 2 nanostructures explored by simple hydrothermal route. The 2D-MoS 2 nanostructures were characterized by powder X-ray diffraction, energy-dispersive X-ray spectroscopy, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and XPS techniques and were immobilized at GCE to obtain MoS 2 -GCE interface. The fabricated interface was characterized by electrochemical impedance spectroscopy which shows less charge transfer resistance and demonstrated superior electrocatalytic properties of the modified surface. The sensing interface was applied for the detection of glucose using amperometry. The MoS 2 -GCE-sensing interface responded effectively as a nonenzymatic glucose sensor (NEGS) over a linearity range of 0.01-0.20 μM with a very low detection limit of 22.08 ng mL -1 . This study demonstrates an easy method for developing a MoS 2 -GCE interface, providing a potential option for the construction of flexible and disposable nonenzymatic glucose sensors (NEGS). Moreover, the fabricated MoS 2 -GCE electrode precisely detected glucose molecules in real blood serum and urine samples of diabetic and nondiabetic persons. These findings suggest that 2D-MoS 2 nanostructured materials show considerable promise as a possible option for hyperglycemia detection and therapy. Furthermore, the development of NEGS might create new prospects in the glucometer industry., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P-gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P-gp, but the observations suggest that P-gp is significant in reducing vildagliptin absorption. Verapamil co-perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co-administration showed a non-significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site-dependent and may be related to the intestinal P-glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug-drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P-glycoprotein level., (© 2024 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd.)

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NO x , Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NO x , Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations., (© 2024. The Author(s).)

Suboptimal fibromyalgia management with over-the-counter analgesics leads to deteriorated outcomes for pain and mental health symptoms especially in low-income countries hosting refugees. To examine the association between the over-the-counter analgesics and the severity of fibromyalgia, depression, anxiety and PTSD symptoms in a cohort of Syrian refugees. This is a cross-sectional study. Fibromyalgia was assessed using the patient self-report survey for the assessment of fibromyalgia. Depression was measured using the Patient Health Questionnaire-9, insomnia severity was measured using the insomnia severity index (ISI-A), and PTSD was assessed using the Davidson trauma scale (DTS)-DSM-IV. Data were analyzed from 291. Among them, 221 (75.9%) reported using acetaminophen, 79 (27.1%) reported using non-steroidal anti-inflammatory drugs (NSAIDs), and 56 (19.2%) reported receiving a prescription for centrally acting medications (CAMs). Fibromyalgia screening was significantly associated with using NSAIDs (OR 3.03, 95% CI 1.58-5.80, p = 0.001). Severe depression was significantly associated with using NSAIDs (OR 2.07, 95% CI 2.18-3.81, p = 0.02) and CAMs (OR 2.74, 95% CI 1.30-5.76, p = 0.008). Severe insomnia was significantly associated with the use of CAMs (OR 3.90, 95% CI 2.04-5.61, p < 0.001). PTSD symptoms were associated with the use of CAMs (β = 8.99, p = 0.001) and NSAIDs (β = 10.39, p < 0.001). Improper analgesics are associated with poor fibromyalgia and mental health outcomes, prompt awareness efforts are required to address this challenge for the refugees and health care providers., (© 2024. The Author(s).)

Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The gut microbiota present in the human digestive system is incredibly varied and is home to trillions of microorganisms. The gut microbiome is shaped at birth, while numerous genetic, dietary, and environmental variables primarily influence the microbiome composition. The importance of gut microbiota on host health is becoming more widely acknowledged. Digestion, intestinal permeability, and immunological and metabolism responses can all be affected by changes in the composition and function of the gut microbiota. There is mounting evidence that the microbial population's complex traits are important biomarkers and indicators of patient outcomes in cancer and its therapies. Numerous studies have demonstrated that changed commensal gut microorganisms contribute to the development and spread of cancer through various routes. Despite the ongoing controversy surrounding the gut microbiome and gastrointestinal cancer, accumulating evidence points to a potentially far more intricate connection than a simple cause-and-effect relationship. SIMPLE SUMMARY: Due to their high frequency and fatality rate, gastrointestinal cancers are regarded as a severe public health issue with complex medical and economic burdens. The gut microbiota may directly or indirectly interact with existing therapies like immunotherapy and chemotherapy, affecting how well a treatment works. The gut microbiome influences the immune response's activity, function, and development. Generally, certain gut bacteria impact the antitumor actions during cancer by creating particular metabolites or triggering T-cell responses. Yet, certain bacterial species have been found to promote cellular proliferation and metastasis in cancer, and comprehending these interactions in the context of cancer may help identify possible treatment targets. Notwithstanding the improvements in the field, additional research is still required to comprehend the underlying processes, examine the effects on existing therapies, and pinpoint certain bacteria and immune cells that can cause this interaction., 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 © 2023. Published by Elsevier Inc.)

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases., (© 2023 International Union of Biochemistry and Molecular Biology.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional Nonstructural protein 14 (NSP14) enzyme, possessing exonuclease and messenger RNA (mRNA) capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscoresthe dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

The complicated relationships between autoimmunity, COVID-19, and COVID-19 vaccinations are described, giving insight into their intricacies. Antinuclear antibodies (ANA), anti-Ro/SSA, rheumatoid factor, lupus anticoagulant, and antibodies against interferon (IFN)-I have all been consistently found in COVID-19 patients, indicating a high prevalence of autoimmune reactions following viral exposure. Furthermore, the discovery of human proteins with structural similarities to SARS-CoV-2 peptides as possible autoantigens highlights the complex interplay between the virus and the immune system in initiating autoimmunity. An updated summary of the current status of COVID-19 vaccines is presented. We present probable pathways underpinning the genesis of COVID-19 autoimmunity, such as bystander activation caused by hyperinflammatory conditions, viral persistence, and the creation of neutrophil extracellular traps. These pathways provide important insights into the development of autoimmune-related symptoms ranging from organ-specific to systemic autoimmune and inflammatory illnesses, demonstrating the wide influence of COVID-19 on the immune system., 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 © 2023 Elsevier B.V. All rights reserved.)

Aims: Physical exercise has been widely recognized for its positive effects on health and well-being. Recently, the impact of exercise on the nervous system has gained attention, with evidence indicating improvements in attention, memory, neurogenesis, and the release of "happiness hormones." One potential mediator of these benefits is Irisin, a myokine induced by exercise that can cross the blood-brain barrier, reduce neuroinflammation, and counteract neurodegeneration. The objective of this study is to conduct a systematic review of animal trials to summarize the neuroprotective effects of Irisin injection in mitigating neuroinflammation and neurodegeneration., Materials and Methods: Two independent reviewers screened three databases (PubMed, Embase, and Google Scholar) in November 2022. Animal studies assessing the neuroprotective effects of Irisin in mitigating neuroinflammation or counteracting neurodegeneration were included. The methodological quality of the included studies was assessed using SYRCLE's Risk of Bias tool., Key Findings: Twelve studies met the inclusion criteria. Irisin injection in rodents significantly reduced neuroinflammation, cytokine cascades, and neurodegeneration. It also protected neurons from damage and apoptosis, reduced oxidative stress, blood-brain barrier disruption, and neurobehavioral deficits following disease or injury. Various mechanisms were suggested to be responsible for these neuroprotective effects. Most of the included studies presented a low risk of bias based on SYRCLE's Risk of Bias tool. Irisin injection demonstrated the potential to alleviate neuroinflammation and counteract neurodegeneration in rodent models through multiple pathways. However, further research is needed to fully understand its mechanism of action and its potential applications in clinical practice and drug discovery., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination ( p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly ( p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive ( p < 0.05) and a Sirt1 decrease ( p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.

Introduction: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients., Areas Covered: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques., Expert Opinion: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of the BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 and 22. This fusion gives rise to the oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The Abl protein intricately regulates the cell cycle by phosphorylating protein tyrosine residues through diverse signaling pathways. In CML, the BCR-ABL fusion protein disrupts the first exon of Abl, leading to sustained activation of tyrosine kinase and resistance to deactivation mechanisms. Pharmacological interventions, such as imatinib, effectively target BCR-ABL's tyrosine kinase activity by binding near the active site, disrupting ATP binding, and inhibiting downstream protein phosphorylation. Nevertheless, the emergence of resistance, often attributed to cap structure mutations, poses a challenge to imatinib efficacy. Current research endeavours are directed towards overcoming resistance and investigating innovative therapeutic strategies. This article offers a comprehensive analysis of the structural attributes of BCR-ABL, emphasizing its pivotal role as a biomarker and therapeutic target in CML. It underscores the imperative for ongoing research to refine treatment modalities and enhance overall outcomes in managing CML., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels. This research endeavors to identify promising inhibitory candidates that target the allosteric site of PCSK9 through an in silico approach. To start with, the FDA-approved Drug Library from Selleckchem was selected and virtually screened by docking studies using Glide extra-precision (XP) docking mode and Smina software (Version 1.1.2). Subsequently, rescoring of 100 drug compounds showing good average docking scores were performed using Gnina software (Version 1.0) to generate CNN Score and CNN binding affinity. Among the drug compounds, amikacin, bestatin, and natamycin were found to exhibit higher docking scores and CNN affinities against the PCSK9 enzyme. Molecular dynamics simulations further confirmed that these drug molecules established the stable protein-ligand complexes when compared to the apo structure of PCSK9 and the complex with the co-crystallized ligand structure. Moreover, the MM-GBSA calculations revealed binding free energy values ranging from -84.22 to -76.39 kcal/mol, which were found comparable to those obtained for the co-crystallized ligand structure. In conclusion, these identified drug molecules have the potential to serve as inhibitors PCSK9 enzyme and these finding could pave the way for the development of new PCSK9 inhibitory drugs in future in vitro research.

The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Addressing the formidable challenge posed by the development of effective and personalized interventions for major depressive disorder (MDD) necessitates a comprehensive comprehension of the intricate role that plasma amino acids play and their implications in MDD pathology and pharmacology. Amino acids, owing to their indispensable functions in neurotransmission, metabolism, and immune regulation, emerge as pivotal entities in this intricate disorder. Our primary objective entails unraveling the underlying mechanisms and unveiling tailored treatments through a meticulous investigation into the interplay between plasma amino acids, MDD, and pharmacological strategies. By conducting a thorough and exhaustive review of the existing literature, we have identified pertinent studies on plasma amino acids in MDD, thereby uncovering noteworthy disturbances in the profiles of amino acids among individuals afflicted by MDD when compared to their healthy counterparts. Specifically, disruptions in the metabolism of tryptophan, phenylalanine, and tyrosine, which serve as precursors to essential neurotransmitters, have emerged as prospective biomarkers and critical contributors to the pathophysiology of depression. Amnio acids play an essential role in MDD and could represent an attractive pharmacological target, more studies are further required to fully reveal their underlying mechanisms., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Gammoh et al.)

The field of microfluidics encompasses the study of fluid behavior within micro-channels and the development of miniature systems featuring internal compartments or passageways tailored for fluid control and manipulation. Microfluidic devices capitalize on the unique chemical and physical properties exhibited by fluids at the microscopic scale. In contrast to their larger counterparts, microfluidic systems offer a multitude of advantages. Their implementation facilitates the investigation and utilization of reduced sample, solvent, and reagent volumes, thus yielding decreased operational expenses. Owing to their compact dimensions, these devices allow for the concurrent execution of multiple procedures, leading to expedited experimental timelines. Over the past two decades, microfluidics has undergone remarkable advancements, evolving into a multifaceted discipline. Subfields such as organ-on-a-chip and paper-based microfluidics have matured into distinct fields of study. Nonetheless, while scientific progress within the microfluidics realm has been notable, its translation into autonomous end-user applications remains a frontier to be fully explored. This paper sets forth the central objective of scrutinizing the present research paradigm, prevailing limitations, and potential prospects of customizable microfluidic devices. Our inquiry revolves around the latest strides achieved, prevailing constraints, and conceivable trajectories for adaptable microfluidic technologies. We meticulously delineate existing iterations of microfluidic systems, elucidate their operational principles, deliberate upon encountered limitations, and provide a visionary outlook toward the future trajectory of microfluidic advancements. In summation, this work endeavors to shed light on the current state of microfluidic systems, underscore their operative intricacies, address incumbent challenges, and unveil promising pathways that chart the course toward the next frontier of microfluidic innovation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Magnetotactic bacteria (MTBs) and their organelles, magnetosomes, are intriguing options that might fulfill the criteria of using bacterial magnetosomes (BMs). The ferromagnetic crystals contained in BMs can condition the magnetotaxis of MTBs, which is common in water storage facilities. This review provides an overview of the feasibility of using MTBs and BMs as nanocarriers in cancer treatment. More evidence suggests that MTBs and BMs can be used as natural nanocarriers for conventional anticancer medicines, antibodies, vaccine DNA, and siRNA. In addition to improving the stability of chemotherapeutics, their usage as transporters opens the possibilities for the targeted delivery of single ligands or combinations of ligands to malignant tumors. Magnetosome magnetite crystals are different from chemically made magnetite nanoparticles (NPs) because they are strong single-magnetic domains that stay magnetized even at room temperature. They also have a narrow size range and a uniform crystal morphology. These chemical and physical properties are essential for their usage in biotechnology and nanomedicine. Bioremediation, cell separation, DNA or antigen regeneration, therapeutic agents, enzyme immobilization, magnetic hyperthermia, and contrast enhancement of magnetic resonance are just a few examples of the many uses for magnetite-producing MTB, magnetite magnetosomes, and magnetosome magnetite crystals. From 2004 to 2022, data mining of the Scopus and Web of Science databases showed that most research using magnetite from MTB was carried out for biological reasons, such as in magnetic hyperthermia and drug delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

The use of biomaterials, such as bacteriophages, as drug delivery vehicles (DDVs) has gained increasing interest in recent years due to their potential to address the limitations of conventional drug delivery systems. Bacteriophages offer several advantages as drug carriers, such as high specificity for targeting bacterial cells, low toxicity, and the ability to be engineered to express specific proteins or peptides for enhanced targeting and drug delivery. In addition, bacteriophages have been shown to reduce the development of antibiotic resistance, which is a major concern in the field of antimicrobial therapy. Many initiatives have been taken to take up various payloads selectively and precisely by surface functionalization of the outside or interior of self-assembling viral protein capsids. Bacteriophages have emerged as a promising platform for the targeted delivery of therapeutic agents, including drugs, genes, and imaging agents. They possess several properties that make them attractive as drug delivery vehicles, including their ability to specifically target bacterial cells, their structural diversity, their ease of genetic manipulation, and their biocompatibility. Despite the potential advantages of using bacteriophages as drug carriers, several challenges and limitations need to be addressed. One of the main challenges is the limited host range of bacteriophages, which restricts their use to specific bacterial strains. However, this can also be considered as an advantage, as it allows for precise and targeted drug delivery to the desired bacterial cells. The use of biomaterials, including bacteriophages, as drug delivery vehicles has shown promising potential to address the limitations of conventional drug delivery systems. Further research is needed to fully understand the potential of these biomaterials and address the challenges and limitations associated with their use., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Plants are increasingly used for the production of high-quality biological molecules for use as pharmaceuticals and biomaterials in industry. Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies. The closure of one of the leading companies in the sector (the Canadian biotech company Medicago Inc., producer of Covifenz) as a result of the withdrawal of investments from the parent company has led to the serious question: What is hindering the exploitation of plant-made biologics to improve health outcomes? Exploring the vast potential of plants as biological factories, this review provides an updated perspective on plant-derived biologics (PDB). A key focus is placed on the advancements in plant-based expression systems and highlighting cutting-edge technologies that streamline the production of complex protein-based biologics. The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems.

Water treatment is crucial in solving the rising people's appetite for water and global water shortages. Carbon nanotubes (CNTs) have considerable promise for water treatment because of their adjustable and distinctive arbitrary, physical, as well as chemical characteristics. This illustrates the benefits and risks of integrating CNT into the traditional water treatment resource. Due to their outstanding adsorbent ability and chemical and mechanical properties, CNTs have gained global consideration in environmental applications. The desalination and extraction capability of CNT were improved due to chemical or physical modifications in pure CNTs by various functional groups. The CNT-based composites have many benefits, such as antifouling performance, high selectivity, and increased water permeability. Nevertheless, their full-scale implementations are still constrained by their high costs. Functionalized CNTs and their promising nanocomposites to eliminate contaminants are advised for marketing and extensive water/wastewater treatment., 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 © 2023. Published by Elsevier Inc.)

Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In modern era, deficiency of Vitamin D3 is predominantly due to limited exposure to sunlight and UV radiation resulting from indoor lifestyles. Several studies have revealed that vitamin D deficiency can lead to chronic vascular inflammation, diabetes mellitus, hypertension, congestive left ventricular hypertrophy, and heart failure. This study introduces a green synthesis of novel bimetallic nanoporous composite, CuO/Ag using lemon extract. The synthesized nanoporous material, CuO/Ag@lemon extract was characterized using several analytical techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The CuO/Ag@lemon extract nanoparticles were immobilized on glassy carbon electrode (GCE) to prepare modified CuO/Ag@lemon extract-GCE interface. The electrocatalytic and electrochemical properties investigation was carried out on the modified electrode. using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and amperometry for detecting of Vitamin D3. The DPV method displayed a linear response range of 0.02-22.5 µM with a detection limit of 2.62 nM, while the amperometric method showed a broader linear range of 0.25-23.25 µM with a detection limit of 2.70 nM with 82% modified electrode stability. The designed electrode exhibited a positive response to the inclusion of Vitamin D3 with electro-oxidation, reaching steady-state within 3.4 s, with 87% reproducibility within a day. The proposed method offers a rapid and sensitive platform for detection of Vitamin D3 with minimal interference from other molecules. The early diagnosis of Vitamin D3 deficiency using modified electrodes allows for early treatment, thereby preventing severe health complications., (© 2023. The Author(s).)

This review explores recent advancements and applications of 3D printing in healthcare, with a focus on personalized medicine, tissue engineering, and medical device production. It also assesses economic, environmental, and ethical considerations. In our review of the literature, we employed a comprehensive search strategy, utilizing well-known databases like PubMed and Google Scholar. Our chosen keywords encompassed essential topics, including 3D printing, personalized medicine, nanotechnology, and related areas. We first screened article titles and abstracts and then conducted a detailed examination of selected articles without imposing any date limitations. The articles selected for inclusion, comprising research studies, clinical investigations, and expert opinions, underwent a meticulous quality assessment. This methodology ensured the incorporation of high-quality sources, contributing to a robust exploration of the role of 3D printing in the realm of healthcare. The review highlights 3D printing's potential in healthcare, including customized drug delivery systems, patient-specific implants, prosthetics, and biofabrication of organs. These innovations have significantly improved patient outcomes. Integration of nanotechnology has enhanced drug delivery precision and biocompatibility. 3D printing also demonstrates cost-effectiveness and sustainability through optimized material usage and recycling. The healthcare sector has witnessed remarkable progress through 3D printing, promoting a patient-centric approach. From personalized implants to radiation shielding and drug delivery systems, 3D printing offers tailored solutions. Its transformative applications, coupled with economic viability and sustainability, have the potential to revolutionize healthcare. Addressing material biocompatibility, standardization, and ethical concerns is essential for responsible adoption., (© 2023. The Author(s).)

We present an enhanced method for synthesizing a novel compound, 1-(4-phenylquinolin-2-yl)propan-1-one ( 3 ), through the solvent-free Friedländer quinoline synthesis using poly(phosphoric acid) as an assisting agent. The crystal structure of compound 3 is analyzed using FT-IR, and the chemical shifts of its 1 H- and 13 C NMR spectra are measured and calculated using B3LYP/6-311G(d,p), CAM-B3LYP/6-311G(d,p), and M06-2X/6-311G(d,p) basis sets in the gas phase. Additionally, the optimized geometry of quinoline 3 is compared with experimental X-ray diffraction values. Through density functional theory calculations, we explore various aspects of the compound's properties, including noncovalent interactions, Hirshfeld surface analysis, nonlinear optical properties, thermodynamic properties, molecular electrostatic potential, and frontier molecular orbitals. These investigations reveal chemically active sites within this quinoline derivative that contribute to its chemical reactivity., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The human endometrium is a complex hormone-target tissue consisting of two layers: the lower basalis, and the upper functionalis. The latter of the two goes through a cycle of thickening and shedding without residual scarring or loss of function. This cycle, known as the menstrual cycle, occurs on a monthly basis in most of healthy reproductive-age women. It is, however, associated with a number of reproductive diseases, endometriosis being one of them. Endometriosis is defined as the presence of endometrium at ectopic sites within the peritoneum or, more rarely, other locations outside the abdominal area. It affects around 6-10% of reproductive-age women in the world and causes debilitating pain, heavy menstrual bleeding, pain during penetrative sex, and infertility. The etiology of the disease is not yet fully understood but the generally accepted theory is that the endometriotic lesions originate from viable eutopic endometrial cells that flow back into the peritoneum through the process of retrograde menstruation. Endometriosis is usually classified into four stages: minimal, mild, moderate, and severe, though it is important to note that the presentation of symptoms does not necessarily correspond to the disease progression. The immune system plays an important role in supporting the viability and growth of ectopic endometriotic tissue, all the while promoting chronic inflammation at the lesion sites, which causes prolonged pain. There is no definitive cure for endometriosis, but there are several options for symptom management, including laparoscopy, hormonal therapy, the use of NSAIDs, dietary changes, exercise, and, in cases when all conservative treatments fail, hysterectomy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

Acetic acid, a colourless liquid organic acid with a characteristic acrid smell, is obtained naturally and has applications in both the food and pharmaceutical industries. It has been reported to have beneficial uses for lifestyle-related diseases, and its efficient disinfectant properties are well known. In this study, an alginate crosslinked with Ca 2+ hydrogel film was treated with acetic acid to explore its biological properties for biomedicine. The results showed that the novel calcium alginate/acetic acid film was biocompatible in vitro using human keratinocyte cells and in vivo with Caenorhabditis elegans . It also had antiviral properties against enveloped and non-enveloped viruses and anticancer properties against melanoma and colon cancer cells. This novel film thus showed promise for the biomedical and pharmaceutical industries, with applications for fabricating broad-spectrum antiviral and anticancer materials.

Purpose: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes., Patients and Methods: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided., Results: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS)., Conclusion: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages., 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 © 2023 Elsevier Inc. All rights reserved.)

Diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) have been receiving increasing attention in the last decade, particularly in the last 5 years, due to their potential to offer a combination of enhanced antimicrobial and mechanical performance. These multi-functional bioactive DLC coatings offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This review begins with an overview of the status and issues with current total joint implant materials and the state-of-the art in DLC coatings and their application to medical implants. A detailed discussion of recent advances in wear resistant bioactive DLC coatings is then presented with a focus on doping the DLC matrix with controlled quantities of Ag and Cu elements. It is shown that both Ag and Cu doping can impart strong antimicrobial potency against a range of Gram-positive and Gram-negative bacteria, but this is always accompanied so far by a reduction in mechanical performance of the DLC coating matrix. The article concludes with discussion of potential synthesis methods to accurately control bioactive element doping without jeopardising mechanical properties and gives an outlook to the potential long-term impact of developing a superior multifunctional bioactive DLC coating on implant device performance and patient health and wellbeing. STATEMENT OF SIGNIFICANCE: Multi-functional diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This article provides a critical review of the state-of-the-art in Ag and Cu doped DLC coatings, beginning with an overview of the current applications of DLC coatings in implant technology followed by a detailed discussion of Ag/Cu doped DLC coatings with particular focus on the relationship between their mechanical and antimicrobial performance. Finally, it ends with a discussion on the potential long-term impact of developing a truly multifunctional ultra-hard wearing bioactive DLC coating to extend the lifetime of total joint implants., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Epigenetics is the study of heritable changes in gene expression or function without altering the DNA sequence. Important factors are part of epigenetic events, such as methylation, DNA histone rearrangements, nucleosome transposition, and non-coding RNAs. Dysregulated epigenetic mechanics are associated with various cancers' initiation, development, and metastasis. It is known that the occurrence and development of cancer can be controlled by regulating unexpected epigenetic events. Epi-drugs are used singly or in combination with chemotherapy and enhance antitumor activity, reduce drug resistance, and stimulate the host immune response. Despite these benefits, epigenetic therapy as a single therapy or in combination with other drugs leads to adverse effects. This review article introduces and compares the advantages, disadvantages, and side effects of using these drugs for the first time since their introduction. Also, this article describes the mechanism of action of various epigenetic drugs. Recommendations for future use of epigenetic drugs as cancer therapeutics are suggested as an overall conclusion., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objective: This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice., Significance: AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications., Methods: The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed., Results: Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury., Conclusions: The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.

Pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. There are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. Exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. They have been verified to be potential biomarkers for pancreatic cancer management. Studying the role of exosomes in pancreatic cancer is substantial. Exosomes are secreted by most eukaryotic cells and participated in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long non-coding RNA, circular RNA, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal miRNAs as possible pancreatic cancer biomarkers. Finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed., (© 2023. The Author(s).)

Alginate is a highly promising biopolymer due to its non-toxic and biodegradable properties. Alginate hydrogels are often fabricated by cross-linking sodium alginate with calcium cations and can be engineered with highly desirable enhanced physical and biological properties for biomedical applications. This study reports on the anticancer, antiviral, antibacterial, in vitro, and in vivo toxicity, water absorption, and compound release properties of an alginate hydrogel crosslinked with calcium and different amounts of zinc cations. The results showed that the calcium alginate hydrogel film crosslinked with the highest amount of zinc showed similar water sorption properties to those of calcium alginate and released a suitable amount of zinc to provide anticancer activity against melanoma and colon cancer cells and has antibacterial properties against methicillin-resistant Staphylococcus epidermidis and antiviral activity against enveloped and non-enveloped viruses. This film is non-toxic in both in vitro in keratinocyte HaCaT cells and in vivo in the Caenorhabditis elegans model, which renders it especially promising for biomedical applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The signalling system known as mammalian target of rapamycin (mTOR) is believed to be required for several biological activities involving cell proliferation. The serine-threonine kinase identified as mTOR recognises PI3K-AKT stress signals. It is well established in the scientific literature that the deregulation of the mTOR pathway plays a crucial role in cancer growth and advancement. This review focuses on the normal functions of mTOR as well as its abnormal roles in cancer development., 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 © 2023 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the potential antidepressant and anxiolytic effects of vitamin C and vitamin D in a stress-induced mouse model of depression, while also exploring the association between these effects and the levels of circulating NOx, periostin, and FKBPL. Our findings revealed that both vitamin C and vitamin D exhibited comparable antidepressant effects to escitalopram, a commonly used antidepressant, without demonstrating any anxiolytic effects. The antidepressant properties of vitamin C and vitamin D were linked to the normalization of Nox and FKBPL levels, while the levels of periostin showed no significant correlation. These results are consistent with previous research, indicating that the antidepressant effects of vitamin C and vitamin D may be attributed to their antioxidant and anti-inflammatory properties, as well as their modulation of neurotransmission and norepinephrine release. Additionally, our study uncovered elevated levels of periostin in stress-induced depression, which were only restored to normal levels by escitalopram, suggesting a potential role for periostin in mood disorders. Furthermore, FKBPL and NOx levels were increased in stress-induced depression and normalized by treatment with vitamin C, vitamin D, and escitalopram, indicating their involvement in the stress response and gene expression regulation. However, it is important to acknowledge certain limitations of our research, such as the use of a single depression induction model and limited dosing regimens. Future investigations should focus on examining these markers in specific brain regions, such as the hippocampus and prefrontal cortex, to gain a more comprehensive understanding of their potential implications for depression. Overall, our findings suggest that vitamin C, vitamin D, and escitalopram may possess antidepressant properties mediated by NOx and FKBPL levels, while emphasizing the potential significance of periostin in the context of depression.

Cancer is one of the diseases that causes a high mortality as it involves unregulated and abnormal cell growth proliferation that can manifest in any body region. One of the typical ovarian cancer symptoms is damage to the female reproductive system. The death rate can be reduced through early detection of the ovarian cancer. Promising probes that can detect ovarian cancer are suitable aptamers. Aptamers, i.e., so-called chemical antibodies, have a strong affinity for the target biomarker and can typically be identified starting from a random library of oligonucleotides. Compared with other probes, ovarian cancer targeting using aptamers has demonstrated superior detection effectiveness. Various aptamers have been selected to detect the ovarian tumor biomarker, vascular endothelial growth factor (VEGF). The present review highlights the development of particular aptamers that target VEGF and detect ovarian cancer at its earliest stages. The therapeutic efficacy of aptamers in ovarian cancer treatment is also discussed.

Objective: This article critically reviews recent research on the use of trimetallic nanomaterials for the fabrication of non-enzymatic glucose sensors (NEGS), also known as fourth-generation glucose sensors (FGGS)., Significance: Diabetes is a prevalent chronic disease worldwide, and glucose monitoring is crucial for its management. However, conventional enzymatic glucose sensors suffer from several technological drawbacks, and there is a need to develop new-generation glucose sensors that can overcome these limitations. NEGS, particularly those composed of trimetallic nanocomposites, have demonstrated promising results in terms of improved shelf life, higher sensitivity, and simplicity of operation during glucose measurement., Methods: In this review, we discuss the different trimetallic nanomaterials developed and used by researchers in recent years for glucose detection, including their mechanisms of action. We also provide a brief discussion of the advantages and disadvantages of FGGS-based trimetallic nanomaterials, as well as the industrial challenges in this area of research., Results: Trimetallic nanomaterials for FGGS have shown excellent reproducibility and high stability, making them suitable for continuous glucose monitoring. The different types of trimetallic nanomaterials have varying sensing properties, and their performance can be tuned by controlling their synthesis parameters., Conclusion: Trimetallic nanomaterials are a promising avenue for the development of FGGS, recent research has demonstrated their potential for glucose monitoring. However, there are still some challenges that need to be addressed before their widespread adoption, such as their long-term stability and cost-effectiveness. Further research in this area is needed to overcome these challenges and to develop commercially viable FGGS for diabetes management.

Purpose: Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent., Methods: A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent., Results: This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers., Conclusions: This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers., (© 2022. The Author(s).)