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Sawsan Mohammed Kareem,1 Israa MS Al-kadmy,1,2 Saba S Kazaal,1 Alaa N Mohammed Ali,1 Sarah Naji Aziz,1 Rabab R Makharita,3 Abdelazeem M Algammal,4 Salim Al-Rejaie,5 Tapan Behl,6 Gaber El-Saber Batiha,7 Mohamed A El-Mokhtar,8 Helal F Hetta8,9 1Branch of Biotechnology, Department of Biology, College of Science, University of Mustansiriyah, Baghdad, Iraq; 2Faculty of Science & Engineering, School of Engineering, University of Plymouth, Plymouth, PL4 8AA, UK; 3Botany Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt; 4Department of Bacteriology, Immunology and Mycology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt; 5Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India; 7Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicines, Damanhour University, Damanhour, 22511, Egypt; 8Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; 9Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USACorrespondence: Helal F HettaUniversity of Cincinnati College of Medicine, Department of Internal Medicine, PO Box 670595, Cincinnati, OH, 45267-0595, USAEmail helal.hetta@uc.eduIsraa MS Al-kadmyFaculty of Science & Engineering, School of Engineering, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, United KingdomEmail israa.al-kadmy@plymouth.ac.ukBackground and Aim: Recently, the extensive use of quinolones led to increased resistance to these antimicrobial agents, with different rates according to the organism and the geographical region. The aim of this study was to detect the resistance rate of Klebsiella pneumoniae Iraqi isolates toward quinolone antimicrobial agents, to determine genetic mutations in gyrA and parC, to screen for efflux-pump activity, and to screen the presence of plasmid-mediated quinolone resistance (PMQR) genes.Methods: Forty-three K. pneumoniae isolates were confirmed phenotypically and genotypically by Vitek 2 system and species specific primers by PCR using the targeting rpo gene followed by sequencing. Antibiotic susceptibility test was carried out using disc diffusion method. Quinolone resistant isolates were subjected to ciprofloxacin MIC testing, and cartwheel method to screen for efflux pump activity. The presence of the plasmid mediated quinolone resistance genes qepA, qnrB, qnrS, and aac(6)Ib was tested by PCR. Sequencing of gyrA and parC was performed.Results: We observed a high rate of resistance to ceftriaxone, gentamicin ciprofloxacin, and levofloxacin. Low rate of resistance was detected against amikacin and azithromycin. Ciprofloxacin MIC results revealed that 96.1% of the isolates had MICs > 256 μg/mL, 83.4% had MICs > 512 μg/mL while 34.6% had MIC > 1024 μg/mL. Testing of isolates against ciprofloxacin mixed with EtBr at various concentrations resulted in decreased resistant. Sequencing results showed that Ser83Leu was the most common mutation in gyrA that was observed in all quinolone resistant isolates, followed by Asp87Asn. Ser80Ile mutation in parC was observed in 77.7% of the tested isolates. The prevalence of PMQR genes was 92.5% aac (6)-Ib, 51.8% qnrB, 40.7% qepA, and 37% qnrS.Conclusion: Quinolone resistance is common in K. pneumoniae isolates in Baghdad. The frequent mutation in gyrA and parC, and the presence of PMQR genes is alarming.Keywords: MDR K. pneumoniae, quinolones resistance gene, PMQR

Introduction. The published data showed the importance of metabolic control in preventing complications in metabolic syndrome (MS) and the role of nutritional medical therapy in glycemic control and in the control of dyslipidemia, hypertension, weight loss/normalization (in overweight or malnourished subjects). Objectives. This study follows the evolution of sarcopenic index (SI) and other clinical parameters (body mass index (BMI), homeostasis evaluation index (HOMA index)) correlated with MS after diet therapy or diet therapy combined with sports, in patients with MS. Patients and methods. Our research was conducted during 12 months, on 110 patients >18 years of age, with HOMA index>2, divided into three groups: control group (CG, N=20), diet therapy group (DTG, N=58), diet therapy and sports group (DTSG, N=32). HOMA index for insulin resistance was calculated as the product of resting plasma insulin (in microunits/milliliter) and plasma glucose (in millimoles/liter), divided by 22.5. SI was determined using BIA, as being the ratio between muscle mass and fat mass, measured in cm2/m2. Results. A significant decrease of BMI (p<0.05) in DTG (from 31.63 to 24.50) and DTSG (from 30.18 to 24.17) vs. CG was observed (Pearson coefficient r=0.281, p<0.001). Weight status changed significantly (p<0.05) in the high-risk patients. There was a significant decrease of HOMA index (p<0.05) in DTG (from 5.93 to 2.57), DTSG (from 3.93 to 2.23), and in CG an increase was observed (from 3.15 to 3.37). Conclusion. The best results in the prevention/ treatment of sarcopenia in MS patients were obtained for DTSG, which benefited from both the positive effect of diet and physical activity. [ABSTRACT FROM AUTHOR]

Cancer ranks among the most life-threatening diseases worldwide and is continuously affecting all age groups. Consequently, many research studies are being carried out to develop new cancer treatments, but many of them experience resistance and cause severe toxicity to the patients. Therefore, there is a continuous need to design novel anticancer agents that are target-based, have a higher potency, and have minimal toxicity. The imidazo[1,2-a]pyridine (IP) pharmacophore has been found to be a prominent moiety in the field of medicinal chemistry due to its vast biological properties. Also, it holds immense potential for combating cancer with minimal side effects, depending on the substitution patterns of the core structure. IPs exhibit significant capability in regulating various cellular pathways, offering possibilities for targeted anticancer effects. The present review summarizes the anticancer profile of numerous IP derivatives synthesized and developed by various researchers from 2016 till now, as inhibitors of phosphoinositide-3-kinase/mammalian target of rapamycin (PI3K/mTOR), protein kinase B/mammalian target of rapamycin (Akt/mTOR), aldehyde dehydrogenase (ALDH), and tubulin polymerization. This review provides a comprehensive analysis of the anticancer activity afforded by the discussed IP compounds, emphasizing the structure-activity-relationships (SARs). The aim is also to underscore the potential therapeutic future of the IP moiety as a potent partial structure for upcoming cancer drug development and to aid researchers in the field of rational drug design., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Alzheimer's disease (AD) is a leading cause of cognitive decline in the aging population, presenting a critical need for early diagnosis and effective prognostic tools. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have emerged as promising biomarkers for AD due to their roles in regulating gene expression and potential for reversibility. This review examines the current landscape of epigenetic biomarkers in AD, emphasizing their diagnostic and prognostic relevance. DNA methylation patterns in genes such as APP, PSEN1, and PSEN2 are highlighted for their strong associations with AD pathology. Alterations in DNA methylation at specific CpG sites have been consistently observed in AD patients, suggesting their utility in early detection. Histone modifications, such as acetylation and methylation, also play a crucial role in chromatin remodelling and gene expression regulation in AD. Dysregulated histone acetylation and methylation have been linked to AD progression, making these modifications valuable biomarkers. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), further contribute to the epigenetic regulation in AD. miRNAs can modulate gene expression post-transcriptionally and have been found in altered levels in AD, while lncRNAs can influence chromatin structure and gene expression. The presence of these non-coding RNAs in biofluids like blood and cerebrospinal fluid positions them as accessible and minimally invasive biomarkers. Technological advancements in detecting and quantifying epigenetic modifications have propelled the field forward. Techniques such as next-generation sequencing, bisulfite sequencing, and chromatin immunoprecipitation assays offer high sensitivity and specificity, enabling the detailed analysis of epigenetic changes in clinical samples. These tools are instrumental in translating epigenetic research into clinical practice. This review underscores the potential of epigenetic biomarkers to enhance the early diagnosis and prognosis of AD, paving the way for personalized therapeutic strategies and improved patient outcomes. The integration of these biomarkers into clinical workflows promises to revolutionize AD management, offering hope for better disease monitoring and intervention., Competing Interests: Declaration of Competing Interest None Declared, (Copyright © 2024. Published by Elsevier B.V.)

For millennia, Cannabis sativa has served diverse roles, from medicinal applications to recreational use. Despite its extensive historical use, only a fraction of its components have been explored until recent times. The therapeutic potential of Cannabis and its constituents has garnered attention, with suggestions for treating various conditions such as Parkinson's disease, epilepsy, Alzheimer's disease, and other Neurological disorders. Recent research, particularly on animal experimental models, has unveiled the neuroprotective properties of cannabis. This neuroprotective effect is orchestrated through numerous G protein-coupled receptors (GPCRs) and the two cannabinoid receptors, CB1 and CB2. While the capacity of cannabinoids to safeguard neurons is evident, a significant challenge lies in determining the optimal cannabinoid receptor agonist and its application in clinical trials. The intricate interplay of cannabinoids with the endocannabinoid system, involving CB1 and CB2 receptors, underscores the need for precise understanding and targeted approaches. Unravelling the molecular intricacies of this interaction is vital to harness the therapeutic potential of cannabinoids effectively. As the exploration of cannabis components accelerates, there is a growing awareness of the need for nuanced strategies in utilizing cannabinoid receptor agonists in clinical settings. The evolving landscape of cannabis research presents exciting possibilities for developing targeted interventions that capitalize on the neuroprotective benefits of cannabinoids while navigating the complexities of receptor specificity and clinical applicability., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xie, Koppula, Kale, Ali, Wankhede, Umare, Upaganlawar, Abdeen, Ebrahim, El-Sherbiny, Behl, Shen and Singla.)

Asthma is a chronic inflammatory condition that affects the airways, posing a substantial health threat to a large number of people worldwide. Bronchodilators effectively alleviate symptoms of airway obstruction by inducing relaxation of the smooth muscles in the airways, thereby reducing breathlessness and enhancing overall quality of life. The drug targeting to lungs poses significant challenges; however, this issue can be resolved by employing nano- and micro-particles drug delivery systems. This review provides brief insights about underlying mechanisms of asthma, including the role of several inflammatory mediators that contribute to the development and progression of this disease. This article provides an overview of the physicochemical features, pharmacokinetics, and mechanism of action of particular groups of bronchodilators, including sympathomimetics, PDE-4 inhibitors (phosphodiesterase-4 inhibitors), methylxanthines, and anticholinergics. This study presents a detailed summary of the most recent developments in incorporation of bronchodilators in nano- and micro-particle-based delivery systems which include solid lipid nanoparticles, bilosomes, novasomes, liposomes, polymeric nano- and micro-particles. Specifically, it focuses on breakthroughs in the categories of sympathomimetics, methylxanthines, PDE-4 inhibitors, and anticholinergics. These medications have the ability to specifically target alveolar macrophages, leading to a higher concentration of pharmaceuticals in the lung tissues., Competing Interests: Competing interestsThe authors declare no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-β plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients., 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 B.V. All rights reserved.)

Gastrointestinal (GI) cancers represent a significant global health challenge, driving relentless efforts to identify innovative diagnostic and therapeutic approaches. Recent strides in microbiome research have unveiled a previously underestimated dimension of cancer progression that revolves around the intricate metabolic interplay between GI cancers and the host's gut microbiota. This review aims to provide a comprehensive overview of these emerging metabolic interactions and their potential to catalyze a paradigm shift in precision diagnosis and therapeutic breakthroughs in GI cancers. The article underscores the groundbreaking impact of microbiome research on oncology by delving into the symbiotic connection between host metabolism and the gut microbiota. It offers valuable insights into tailoring treatment strategies to individual patients, thus moving beyond the traditional one-size-fits-all approach. This review also sheds light on novel diagnostic methodologies that could transform the early detection of GI cancers, potentially leading to more favorable patient outcomes. In conclusion, exploring the metabolic interactions between host gut microbiota and GI cancers showcases a promising frontier in the ongoing battle against these formidable diseases. By comprehending and harnessing the microbiome's influence, the future of precision diagnosis and therapeutic innovation for GI cancers appears more optimistic, opening doors to tailored treatments and enhanced diagnostic precision., 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.)

Misfolded and aggregated proteins build up in neurodegenerative illnesses, which causes neuronal dysfunction and ultimately neuronal death. In the last few years, there has been a significant upsurge in the level of interest towards the function of molecular chaperones in the control of misfolding and aggregation. The crucial molecular chaperones implicated in neurodegenerative illnesses are covered in this review article, along with a variety of their different methods of action. By aiding in protein folding, avoiding misfolding, and enabling protein breakdown, molecular chaperones serve critical roles in preserving protein homeostasis. By aiding in protein folding, avoiding misfolding, and enabling protein breakdown, molecular chaperones have integral roles in preserving regulation of protein balance. It has been demonstrated that aging, a significant risk factor for neurological disorders, affects how molecular chaperones function. The aggregation of misfolded proteins and the development of neurodegeneration may be facilitated by the aging-related reduction in chaperone activity. Molecular chaperones have also been linked to the pathophysiology of several instances of neuron withering illnesses, enumerating as Parkinson's disease, Huntington's disease, and Alzheimer's disease. Molecular chaperones have become potential therapy targets concerning with the prevention and therapeutic approach for brain disorders due to their crucial function in protein homeostasis and their connection to neurodegenerative illnesses. Protein homeostasis can be restored, and illness progression can be slowed down by methods that increase chaperone function or modify their expression. This review emphasizes the importance of molecular chaperones in the context of neuron withering disorders and their potential as therapeutic targets for brain disorders., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is a condition initiated by the assimilation of β-amyloid plaques (Aβ) and tau tangles, leading to neurodegeneration. It involves frequently cognitive decline as well as memory impairment in patients. Efforts in therapeutic interventions are currently facing challenges in identifying targets within this scaffold that can significantly alter the clinical course for individuals with AD. Moreover, in AD, neurons release a protein called endostatin, which accumulates in Aβ plaques and enhances AD. This accumulation of Aβ in the triggers a cascade of events leading to synaptic dysfunction, neuroinflammation, and ultimately neuronal death. Environmental factors nowadays increase the risk of AD with prolonged exposure of heavy metals such as copper (Cu), lead (Pb), mercury (Hg), cadmium (Cd), and other pesticides. It has been observed that these factors can cause the aggregation of Aβ and tau which initiates the plaque formation and hence leads to enhanced pathogenesis of AD. This review summarizes the interlinking between heavy metals, environmental factors, pesticides, endostatin, and progression of AD has been deliberated with recent findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses., Methodology: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer., Results: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations., Conclusion: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression., 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 GmbH. All rights reserved.)

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option., 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.

Introduction: Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning and in-silico predictions, scarcity of data hampers accurate prediction of drug candidates' pharmacokinetic properties., Areas Covered: The study highlights current developments in human pharmacokinetic prediction, talks about attempts to apply synthetic approaches for molecular design, and searches several databases, including Scopus, PubMed, Web of Science, and Google Scholar. The article stresses importance of rigorous analysis of machine learning model performance in assessing progress and explores molecular modeling (MM) techniques, descriptors, and mathematical approaches. Transitioning to clinical drug development, article highlights AI (Artificial Intelligence) based computer models optimizing trial design, patient selection, dosing strategies, and biomarker identification. In-silico models, including molecular interactomes and virtual patients, predict drug performance across diverse profiles, underlining the need to align model results with clinical studies for reliability. Specialized training for human specialists in navigating predictive models is deemed critical. Pharmacogenomics, integral to personalized medicine, utilizes predictive modeling to anticipate patient responses, contributing to more efficient healthcare system. Challenges in realizing potential of predictive modeling, including ethical considerations and data privacy concerns, are acknowledged., Expert Opinion: AI models are crucial in drug development, optimizing trials, patient selection, dosing, and biomarker identification and hold promise for streamlining clinical investigations.

Alzheimer's disease (AD) is the most common type of dementia accounting for 90% of cases; however, frontotemporal dementia, vascular dementia, etc. prevails only in a minority of populations. The term dementia is defined as loss of memory which further takes several other categories of memories like working memory, spatial memory, fear memory, and long-term, and short-term memory into consideration. In this review, these memories have critically been elaborated based on context, duration, events, appearance, intensity, etc. The most important part and purpose of the review is the various pathological cascades as well as molecular levels of targets of AD, which have extracellular amyloid plaques and intracellular hyperphosphorylated tau protein as major disease hallmarks. There is another phenomenon that either leads to or arises from the above-mentioned hallmarks, such as oxidative stress, mitochondrial dysfunction, neuroinflammation, cholinergic dysfunction, and insulin resistance. Several potential drugs like antioxidants, anti-inflammatory drugs, acetylcholinesterase inhibitors, insulin mimetics or sensitizers, etc. studied in various previous preclinical or clinical reports were put as having the capacity to act on these pathological targets. Additionally, agents directly or indirectly targeting amyloid and tau were also discussed. This could be further investigated in future research., 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 B.V. All rights reserved.)

Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zheng, Kumar, Sharma, Behl, Sehgal, Wal, Shinde, Kawaduji, Kapoor, Anwer, Gulati, Shen, Singla and Bungau.)

Kirsten rat sarcoma (KRAS) stands out as the most prevalent mutated oncogene, playing a crucial role in the initiation and progression of various cancer types, including colorectal, lung and pancreatic cancer. The oncogenic modifications of KRAS are intricately linked to tumor development and are identified in 22% of cancer patients. This has spurred the necessity to explore inhibition mechanisms, with the aim of investigating and repurposing existing drugs for diagnosing cancers dependent on KRAS G12C In this investigation, 26 nucleoside-based drugs were collected from literature to assess their effectiveness against KRAS G12C. The study incorporates in-silico molecular simulations and molecular docking examinations of these nucleoside-derived drugs with the KRAS G12C protein using Protein Data Bank (PDB) ID: 5V71. The docking outcomes indicated that two drugs, Azacitidine and Ribavirin, exhibited substantial binding affinities of -8.7 and -8.3 kcal/mol, respectively. These drugs demonstrated stability in binding to the active site of the protein during simulation studies. Root mean square deviation (RMSD) analyses indicated that the complexes closely adhered to an equilibrium RMSD value ranging from 0.17 to 0.2 nm. Additionally, % occupancies, bond angles and the length of hydrogen bonds were calculated. These findings suggest that Azacitidine and Ribavirin may potentially serve as candidates for repurposing in individuals with KRAS-dependent cancers.Communicated by Ramaswamy H. Sarma.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling.

Inflammation is an individual's physiological response to a sequence of physical, chemical, or infectious stressors acting mainly to provide localized protection. Although inflammation is a protective and thus beneficial process, its excess or prolonged action can be harmful to the body. An increasing number of the population worldwide are changing their lifestyles, which leads to a rise in inflammatory diseases, such as atherosclerosis, angina pectoris, myocardial infarction, ulcerative colitis, cancer, and many more. Their treatment is based majorly on the pharmacological approach. However, natural products or bioactive compounds are of great significance in inflammation therapy because they show minimum side effects and maximum bioavailability. Therefore, it is critical to investigate bioactive substances that can modify target functions associated with oxidative stress defense and might be used to achieve various health benefits. This review accentuates the essence of bioactive chemicals used in the treatment of inflammation and other inflammatory illnesses. These bioactive compounds can be of any origin, such as plants, animals, bacteria, fungi, marine invertebrates, etc. Bioactive compounds derived from plant sources, such as glycyrrhizin, lignans, lycopene, resveratrol, indoles, and phenolic and polyphenolic compounds, work mainly by reducing oxidative stress and thereby preventing various inflammatory disorders. A large diversity of these anti-inflammatory bioactive compounds has also been discovered in marine environments, giving rise to an increase in the interest of various scientists in marine invertebrates and microbes. The vast diversity of microbes found in the marine environment represents an enormous supply to extract novel compounds, such as from bacteria, cyanobacteria, fungi, algae, microalgae, tiny invertebrates, etc. In the present review, an attempt has been made to summarize such novel bioactive compounds that help prevent inflammatory responses via different mechanisms of action., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurodegenerative disorders are distinguished by the progressive loss of anatomically or physiologically relevant neural systems. Atypical mitochondrial morphology and metabolic malfunction are found in many neurodegenerative disorders. Alteration in mitochondrial function can occur as a result of aberrant mitochondrial DNA, altered nuclear enzymes that interact with mitochondria actively or passively, or due to unexplained reasons. Mitochondria are intimately linked to the Endoplasmic reticulum (ER), and ER-mitochondrial communication governs several of the physiological functions and procedures that are disrupted in neurodegenerative disorders. Numerous researchers have associated these disorders with ER-mitochondrial interaction disturbance. In addition, aberrant mitochondrial DNA mutation and increased ROS production resulting in ionic imbalance and leading to functional and structural alterations in the brain as well as cellular damage may have an essential role in disease progression via mitochondrial malfunction. In this review, we explored the evidence highlighting the role of mitochondrial alterations in neurodegenerative pathways in most serious ailments, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Lung cancer's enduring global significance necessitates ongoing advancements in diagnostics and therapeutics. Recent spotlight on proteomic and genetic biomarker research offers a promising avenue for understanding lung cancer biology and guiding treatments. This review elucidates genetic and proteomic lung cancer biomarker progress and their treatment implications. Technological strides in mass spectrometry-based proteomics and next-generation sequencing enable pinpointing of genetic abnormalities and abnormal protein expressions, furnishing vital data for precise diagnosis, patient classification, and customized treatments. Biomarker-driven personalized medicine yields substantial treatment improvements, elevating survival rates and minimizing adverse effects. Integrating omics data (genomics, proteomics, etc.) enhances understanding of lung cancer's intricate biological milieu, identifying novel treatment targets and biomarkers, fostering precision medicine. Liquid biopsies, non-invasive tools for real-time treatment monitoring and early resistance detection, gain popularity, promising enhanced management and personalized therapy. Despite advancements, biomarker repeatability and validation challenges persist, necessitating interdisciplinary efforts and large-scale clinical trials. Integrating artificial intelligence and machine learning aids analyzing vast omics datasets and predicting treatment responses. Single-cell omics reveal cellular connections and intratumoral heterogeneity, valuable for combination treatments. Biomarkers enable accurate diagnosis, tailored medicines, and treatment response tracking, significantly impacting personalized lung cancer care. This approach spurs patient-centered trials, empowering active patient engagement. Lung cancer proteomic and genetic biomarkers illuminate disease biology and treatment prospects. Progressing towards individualized efficient therapies is imminent, alleviating lung cancer's burden through ongoing research, omics integration, and technological strides., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest in the submission of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cancer is one of the most widespread and severe diseases with a huge mortality rate. In recent years, the second-leading mortality rate of any cancer globally has been breast cancer, which is one of the most common and deadly cancers found in women. Detecting breast cancer in its initial stages simplifies treatment, decreases death risk, and recovers survival rates for patients. The death rate for breast cancer has risen to 0.024 % in some regions. Sensitive and accurate technologies are required for the preclinical detection of BC at an initial stage. Biomarkers play a very crucial role in the early identification as well as diagnosis of women with breast cancer. Currently, a wide variety of cancer biomarkers have been discovered for the diagnosis of cancer. For the identification of these biomarkers from serum or other body fluids at physiological amounts, many detection methods have been developed. In the case of breast cancer, biomarkers are especially helpful in discovering those who are more likely to develop the disease, determining prognosis at the time of initial diagnosis and choosing the best systemic therapy. In this study we have compiled various clinical aspects and signaling pathways associated with protein-based biomarkers and gene-based biomarkers., 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.)

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Reactive oxygen species (ROS) play a crucial role in cell survival regulation, and its low levels may act as indicators to encourage cellular proliferation. In contrast, elevated levels of ROS may lead to apoptosis. Stability between generating and eliminating ROS allows the retention of effective functioning of redox-sensitive signaling proteins under physiologic conditions. Cells typically maintain redox homeostasis to guarantee appropriate responses to internal and external stimuli. However, oxidative stress occurs when the oxidation product level exceeds the number of standard antioxidant systems. ROS can cause harm to all types of hepatic cells, including endothelial cells, hepatocytes, Kupffer cells, and stellate cells. High levels of ROS may lead to tissue edema, ischemia, fibrosis, cell death, or malignant transformation and may eventually lead to complete tissue damage. Antioxidants in our body exist in a homeostatic balance with other enzymes involved in the repair of cellular functions in addition to the non-enzymatic molecules such as urate, bilirubin, several vitamins, and reduced glutathione to maintain the levels of ROS in the interest of cellular homeostasis. This balance may, however, get disturbed in case of acute or chronic liver injury due to the accumulation of ROS. In the current manuscript, we aim to review the relevance of oxidative stress and its indicator of liver injury in chronic liver diseases such as alcoholic and non-alcoholic fatty liver diseases and hepatitis. Since reactive oxidation species may also lead to lipid peroxidation and promote ferroptosis, we have also evaluated their impact on epigenetic modifications, such as oxidative damage to histone proteins and DNA methylation, and the differential expression of genes related to cellular injury. We also want to highlight the potential of traditional herbal medicines as redox regulators for managing chronic liver diseases., Competing Interests: None., (AJTR Copyright © 2023.)

Tecoma stans (Fam. Bignoniaceae) is also popularly known as yellow bells and yellow trumpet bush in vernacular terminology. Limited and variable data are available from the literature regarding the quantification of luteolin, apigenin and chrysoeriol, which are considered as the most active pharmacological active constituents. High-performance liquid chromatography-photodiode array detection has been developed for the determination of the bioactive flavonoids, luteolin, apigenin and chrysoeriol, from the methanolic extract of the leaves of T. stans. A column packed with a pentafluorophenyl-based stationary phase was used for the separation of the analytes under gradient elution. The detection wavelength was 345 nm. The validation of the method as per the International Council on Harmonisation (ICH) guidelines (ICH 2005) for linearity, accuracy and precision was investigated and found within limits specified by the ICH guidelines. The method was linear over with a good regression coefficient of more than 0.99. The limit of detection of the method was 0.68, 2.97 and 1.76 μg/mL for luteolin, apigenin and chrysoeriol, respectively. In conclusion, a reliable and reproducible method was devised that can be used for the estimation of the said components from T. stans., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Ischemic preconditioning ( IPC) is the utmost capable design to achieve protection over ischemia-reperfusion injury (I/R), but this phenomenon gets attenuated during various pathological conditions like diabetes. Chrysin exhibits cardioprotection in various experiments however, its therapeutic potential on IPC-mediated cardioprotection via PI3K-Akt-eNOS pathway in streptozotocin (STZ) triggered diabetes-challenged rat heart is yet to be assessed. For that reason, the experiment has been planned to investigate chrysin's effect on the cardioprotective action of IPC involving the PI3K-Akt-eNOS cascade in rat hearts challenged to diabetes., Methods: The project was accomplished through means of absorbance studies for biochemical parameters, infarct size measurement (TTC stain) and coronary flow., Results: The findings of the present study revealed that STZ drastically augmented the serum glucose level and the chrysin significantly reversed the IPC-stimulated increased coronary flow, nitrite release, and reduced LDH (lactate dehydrogenase), CK-MB (creatine kinase) activities as well as infarct size in diabetes-induced rat heart. Furthermore, chrysin also reversed the IPC-induced reduction in oxidative stress in an isolated Langendorff's perfused diabetic rat heart. Moreover, four episodes of preconditioning by either PI3K or eNOS inhibitor in chrysin-pretreated diabetic rat hearts significantly abolished the protective effect of chrysin., Conclusion: Consequently, these observations suggested that chrysin increases the therapeutic efficiency of IPC in mitigating I/R injury via PI3K-Akt-eNOS signalling in diabetes-challenged rat hearts. Hence, chrysin could be a potential alternative option to IPC in diabetic rat hearts., 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., (© 2023 Published by Elsevier Ltd.)

Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma., Competing Interests: None, (© 2023 The Authors.)

Cross-sectional studies, while not considered glamorous endeavors, are firmly anchored in data and statistics, providing essential insights about public health. The aim of the study is to see the frequency of hepatoprotective (HP) nutritional supplement consumption among patients with chronic diseases (other than chronic liver disorders) and analyzes the habits related to the consumption of nutritional supplements among these patients. A total of 954 patients, seeking medical prescriptions for chronic diseases under various payment arrangements (compensated, gratuity, or full payment) were carefully selected over a 12-month period from four private pharmaceutical facilities. We examined the frequency of HP consumption in relation with a number of prescribed medications for chronic conditions. All these patients were invited to complete a questionnaire about their supplement consumption habits and were provided the option to participate in a nutritional status assessment. One hundred ninety-five patients consented to participate in the survey, and 65 patients agreed to undergo a nutritional status evaluation. Of the 954 patients, 77.2% incorporate HP into their regimen. The most frequent consumption (83.33%) was recorded in a group with seven drugs, followed by a group with three drugs (82.84%). Women have a higher usage rate of HP (80.58%; 444 from 551) compared to men (62.60%; 293 from 383), and most of the patients (59.5%) used extracts of Silybum marianum L. In the survey, 64.61% of participants were using supplements, with most (59.52%) consuming HP. Only 32.54% of patients rely on recommendations from healthcare professionals. Of the patients who use supplements, 55.56% reported improvements in their health status. Furthermore, patients who integrate supplements into their daily routine tend to achieve better overall nutritional status.