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Objective: This study examined the prevalence and correlates of fibromyalgia and insomnia in a convenience sample of Women with Multiple Sclerosis (WMS). Methods: The study was cross-sectional in design and recruited a sample of 163 women with Relapsing-Remitting Multiple Sclerosis (RRMS). Fibromyalgia was assessed using the Patient Self-Report Survey (PSRS), which follows criteria outlined by the American College of Rheumatology. Insomnia was measured using the Arabic version of the Insomnia Severity Index (ISI-A). Results: The prevalence of fibromyalgia and insomnia was 28.2% (n = 46) and 46.3% (n = 76), respectively. Multivariate analyses were used to determine significant independent correlates. Fibromyalgia was associated with age above 40 years (OR = 2.29, 95% CI = 1.01-5.18, P =.04), high school education (OR = 3.69, 95% CI = 1.62-8.37, P =.002), and non-use of analgesics (OR =.02, 95% CI =.004-.21, P =.001). Insomnia symptoms were significantly associated only with age above 40 years (OR = 2.16, 95% CI = 1.16-4.04, P =.01). Conclusion: These findings highlight the need for increased attention by primary care physicians towards diagnosing and treating fibromyalgia and insomnia among women with RRMS in Jordan, particularly for older women. [ABSTRACT FROM AUTHOR]

Introduction: Incretin-based therapies have emerged as effective treatments for type 2 diabetes (T2D) and obesity. However, not all patients achieve optimal outcomes with existing treatments, highlighting the need for more effective solutions. Areas covered: We present a comprehensive evaluation of Tirzepatide (TZP), a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, for managing obesity and T2D. We conducted a systematic search of Cochrane, PubMed, Scopus, and Web of Science databases from inception to April 2024. The focus of the review is on the development and therapeutic potential of TZP, with detailed exploration on pharmacodynamics, pharmacokinetics, clinical efficacy, and safety. Furthermore, it reviews TZP's impacts on glycemic control, weight management, and its potential cardiovascular (CV) benefits. Expert opinion: TZP represents a significant advancement in the dual-targeted approach to treating T2D and obesity. Its unique mechanism of action offers superior efficacy in reducing glycemic levels and body weight compared to existing therapies. New data suggesting improvements in CV outcomes indicate that TZP could set a new standard in the treatment paradigm. While long-term data on efficacy and safety are still forthcoming, current evidence positions TZP as a promising option for patients who have not reached their therapeutic goals with existing treatments. [ABSTRACT FROM AUTHOR]

Nanomaterial synthesis is a growing study area because of its extensive range of uses. Nanoparticles' high surface‐to‐volume ratio and rapid interaction with various particles make them appealing for diverse applications. Traditional physical and chemical methods for creating metal nanoparticles are becoming outdated because they involve complex manufacturing processes, high energy consumption, and the formation of harmful by‐products that pose major dangers to human health and the environment. Therefore, there is an increasing need to find alternative, cost‐effective, dependable, biocompatible, and environmentally acceptable ways of producing nanoparticles. The process of synthesizing nanoparticles using microbes has become highly intriguing because of their ability to create nanoparticles of varying sizes, shapes, and compositions, each with unique physicochemical properties. Microbes are commonly used in nanoparticle production because they are easy to work with, can use low‐cost materials, such as agricultural waste, are cheap to scale up, and can adsorb and reduce metal ions into nanoparticles through metabolic activities. Biogenic synthesis of nanoparticles provides a clean, nontoxic, ecologically friendly, and sustainable method using renewable ingredients for reducing metals and stabilizing nanoparticles. Nanomaterials produced by bacteria can serve as an effective pollution control method due to their many functional groups that can effectively target contaminants for efficient bioremediation, aiding in environmental cleanup. At the end of the paper, we will discuss the obstacles that hinder the use of biosynthesized nanoparticles and microbial‐based nanoparticles. The paper aims to explore the sustainability of microorganisms in the burgeoning field of green nanotechnology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Epigenetics plays a significant role in understanding depression, which is considered one of the most complex mental health disorders. Epigenetics includes all changes in gene expression that do not involve any modifications to DNA sequences. In depression, epigenetic changes may affect the activation or suppression of specific genes involved in mood regulation. Scientists have attempted to determine how specific environmental factors, such as stress or trauma, can trigger epigenetic changes that are closely linked to gene function. By studying these mechanisms, researchers have developed effective treatments and interventions for depression. This discovery not only provides a better understanding of the biological basis of depression, but also suggests new approaches for highly personalized treatments that may be available to individuals suffering from this widespread mental health disorder in the near future. Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies. [ABSTRACT FROM AUTHOR]

Overcoming the blood–brain barrier (BBB) remains a substantial challenge in CNS drug delivery. This review explores the potential of lipid-based nanoparticles (NPs) such as liposomes and solid lipid NPs to overcome this obstacle. As demonstrated in preclinical studies, these lipid-based NPs exhibit the capacity to breach the BBB via receptor-mediated transcytosis and surface modifications. By capitalizing on enhanced permeability and retention, they ensure efficient transport and accumulation within the brain, which has profound implications in neuroscience and therapeutics. Lipid-based NPs facilitate targeted drug delivery to specific brain regions, enhance therapeutic outcomes, and minimize off-target effects. Combining NPs with techniques such as ultrasound or gene editing shows promise for addressing transport challenges. However, realizing their full potential demands further research, including scalable manufacturing, understanding the long-term CNS fate, and establishing reliable BBB models. These advancements promise secure and effective utilization of lipid-based NPs in CNS therapeutics, ultimately advancing patient care and neuroscience. In conclusion, this review highlights the significant potential to overcome the BBB and enable effective CNS drug delivery. The unprecedented opportunities presented by these NPs have the potential to revolutionize the treatment of neurological disorders, heralding a new era of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4–1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) possess unmatched chemical, biological, and physical properties that make them unique compounds as antimicrobial, antifungal, antiviral, and anticancer agents. With the increasing drug resistance, AgNPs serve as promising entities for targeted drug therapy against several bacterial, fungal, and viral components. In addition, AgNPs also serve as successful anticancer agents against several cancers, including breast, prostate, and lung cancers. Several works in recent years have been done towards the development of AgNPs by using plant extracts like flowers, leaves, bark, root, stem, and whole plant parts. The green method of AgNP synthesis thus has several advantages over chemical and physical methods, especially the low cost of synthesis, no toxic byproducts, eco-friendly production pathways, can be easily regenerated, and the bio-reducing potential of plant derived nanoparticles. Furthermore, AgNPs are biocompatible and do not harm normally functioning human or host cells. This review provides an exhaustive overview and potential of green synthesized AgNPs that can be used as antimicrobial, antifungal, antiviral, and anticancer agents. After a brief introduction, we discussed the recent studies on the development of AgNPs from different plant extracts, including leaf parts, seeds, flowers, stems, bark, root, and whole plants. In the following section, we highlighted the different therapeutic actions of AgNPs against various bacteria, fungi, viruses, and cancers, including breast, prostate, and lung cancers. We then highlighted the general mechanism of action of AgNPs. The advantages of the green synthesis method over chemical and physical methods were then discussed in the article. Finally, we concluded the review by providing future perspectives on this promising field in nanotechnology. [ABSTRACT FROM AUTHOR]

A significant driving force behind the brisk research on rechargeable batteries, particularly lithium-ion batteries (LiBs) in high-performance applications, is the development of portable devices and electric vehicles. Carbon-based materials, which have finite specific capacity, make up the anodes of LiBs. Many attempts are being made to produce novel nanostructured composite anode materials for LiBs that display cycle stability that is superior to that of graphite using graphene oxide. Therefore, using significant amounts of waste graphene oxide from used LiBs represents a fantastic opportunity to engage in waste management and circular economy. This review outlines recent studies, developments and the current advancement of graphene oxide-based LiBs, including preparation of graphene oxide and utilization in LiBs, particularly from the perspective of energy storage technology, which has drawn more and more attention to creating high-performance electrode systems. [ABSTRACT FROM AUTHOR]

Simple Summary: This review assesses the integration of nanotechnology and immunotherapy, with a specific focus on the utilization of nanomaterials to modulate the immune system in conditions such as cancer and autoimmunity. Liposomes, polymers, and inorganic nanoparticles (NPs) are versatile nanomaterials capable of effectively transporting immunomodulatory molecules. Their interactions with immune cells have contributed to the development of checkpoint inhibitors, improved cancer vaccines, and the optimization of adoptive cell therapies. These approaches enable the fine-tuning of immune responses with minimal adverse effects. Positioned at the forefront of the convergence of nanotechnology and immunology, nanomaterial-based platforms have the potential to revolutionize patient-centered immunotherapy. These systems are used in the transformative era of disease management by prioritizing safety, personalization, and compliance with regulations. Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could push current technological frontiers and provide new and innovative solutions for immune-related disorders and diseases without off-target effects. These materials enable targeted interactions with immune cells, thereby enhancing the effectiveness of checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. Moreover, they allow for fine-tuning of immune responses while minimizing side effects. At the intersection of nanotechnology and immunology, nanomaterial-based platforms have immense potential to revolutionize patient-centered immunotherapy and reshape disease management. By prioritizing safety, customization, and compliance with regulatory standards, these systems can make significant contributions to precision medicine, thereby significantly impacting the healthcare landscape. [ABSTRACT FROM AUTHOR]

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 NOx, 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 NOx, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is classified under postpartum psychiatric disorders and initiates soon after birthing, eliciting neuropsychological and behavioral deficits in mothers and offspring. Globally, PPD is estimated to be associated with 130–190 per 1000 birthing. The severity and incidences of PPD have aggravated in the recent years due to the several unfavorable environmental and geopolitical circumstances. The purpose of this systematic review hence is to explore the contributions of recent circumstances on the pathogenesis and incidence of PPD. The search, selection and retrieval of the articles published during the last three years were systematically performed. The results from the primary studies indicate that unfavorable contemporary socio-geopolitical and environmental circumstances (e.g. Covid-19 pandemic, political conflicts/wars, and natural calamities; such as floods and earthquakes) detrimentally affect PPD etiology. A combination of socio-economic and psychological factors, including perceived lack of support and anxiousness about the future may contribute to drastic aggravation of PPD incidences. Finally, we outline some of the potential treatment regimens (e.g. inter-personal psycho- and art-based therapies) that may prove to be effective in amelioration of PPD-linked symptoms in birthing women, either alone or in complementation with traditional pharmacological interventions. We propose these psychological and art-based intervention strategies may beneficially counteract the negative influences of the unfortunate recent events across multiple cultures, societies and geographical regions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The rising foodborne disease outbreaks poses significant challenges to key objectives in food microbiology. This trend is primarily attributed to global population growth and intensified food production. A thorough microbiological assessment of end products is therefore crucial. Methods: We evaluated the bacterial presence and abundance in various dairy products (sour cream, cottage cheese, buttercream, cream cheese, pasteurized milk, protein-rich milk, and yogurt) sourced from a local supermarket in Bosnia and Herzegovina. Two enumeration methods (pour plating and most probable number) were employed alongside morphological, biochemical, and molecular analyses (Gram staining, oxidase test, catalase test, indole test, lipolytic activity assay, and RT-qPCR). Our focus was on spoilage-causing lactic acid bacteria (LAB), hygiene indicator thermotolerant coliforms (TC), and the foodborne pathogen Salmonella spp. Results: Six out of seven dairy products harbored high levels of LAB, suggesting potential spoilage, with the exception of cottage cheese. Additionally, both TC and Escherichia coli exceeded acceptable microbial limits, particularly in pasteurized milk. Furthermore, initial tests detected presumptive Salmonella spp. in cream cheese, protein-rich milk, and yogurt. Conclusion: These results highlight the need for stringent sanitary practices during dairy production to extend product shelf-life and prevent premature spoilage from unwanted bacterial presence. Moreover, eliminating pathogen contamination during manufacturing is crucial to mitigate serious food safety risks, including potential food poisoning. [ABSTRACT FROM AUTHOR]

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 Ca2+ 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of respiratory illnesses that primarily affects children, particularly those under 2 years old, and adults. RSV infections can lead to hospitalization and even mortality. The virus is transmitted through respiratory droplets spread by coughing or sneezing. We conducted an extensive literature search focused on RSV, pathogenicity and relevant keywords like 'RSV treatment,' 'RSV vaccine,' and 'RSV diagnosis' to explore effective treatment strategies, advances in potential RSV vaccines and ongoing clinical trials, and progress in diagnostic techniques for accurate and timely detection of RSV infections. These findings are crucial for developing appropriate management and control measures. Respiratory syncytial virus (RSV) is a virus that causes respiratory illness. It mainly affects infants, children and older adults and is spread by coughing, sneezing and direct contact. Symptoms can be mild and cold-like or can become serious breathing problems. There is no specific treatment or vaccine against the virus. Symptoms can be managed but those who become particularly poorly may need to go to the hospital. Some people at high risk of serious illness may be able to receive preventive treatments. To prevent illness, the population should practice good hand hygiene and avoid close contact with the sick, particularly in the case of infants and young children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the advancement of biomedical research into antimicrobial treatments for various diseases, the source and delivery of antibiotics have attracted attention. In periodontal diseases, antibiotics are integral in positive treatment outcomes; however, the use of antibiotics is with caution as the potential for the emergence of resistant strains is of concern. Over the years, conventional routes of drug administration have been proven to be effective for the treatment of PD, yet the problem of antibiotic resistance to conventional therapies continues to remain a setback in future treatments. Hydrogels fabricated from natural and synthetic polymers have been extensively applied in biomedical sciences for the delivery of potent biological compounds. These polymeric materials either have intrinsic antibacterial properties or serve as good carriers for the delivery of antibacterial agents. The biocompatibility, low toxicity and biodegradability of some hydrogels have favoured their consideration as prospective carriers for antibacterial drug delivery in PD. This article reviews PD and its antibiotic treatment options, the role of bacteria in PD and the potential of hydrogels as antibacterial agents and for antibiotic drug delivery in PD. Finally, potential challenges and future directions of hydrogels for use in PD treatment and diagnosis are also highlighted. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines have been widely used to reduce the incidence and disease severity of COVID-19. Questions have lately been raised about the possibility of an association between COVID-19 vaccines and myocarditis, an inflammatory condition affecting the myocardium, or the middle layer of the heart. Myocarditis can be caused by infections, immune reactions, or toxic exposure. The incidence rate of myocarditis and pericarditis was calculated to be 5.98 instances per million COVID-19 vaccine doses delivered, which is less than half of the incidences after SARS-CoV-2 infection. Myocarditis rates in people aged 12 to 39 years are around 12.6 cases per million doses following the second dose of mRNA vaccination. Adolescent men are more likely than women to develop myocarditis after receiving mRNA vaccines. The objectives of this systematic review and meta-analysis are to find out how often myocarditis occurs after receiving the COVID-19 vaccine, as well as the risk factors and clinical repercussions of this condition. Nevertheless, the causal relationship between vaccination and myocarditis has been difficult to establish, and further research is required. It is also essential to distinguish between suggested cases of myocarditis and those confirmed by endomyocardial biopsy. [ABSTRACT FROM AUTHOR]

The escalating risk of diabetes and its consequential impact on cardiac, vascular, ocular, renal, and neural systems globally have compelled researchers to devise cost-effective, ultrasensitive, and reliable electrochemical glucose sensors for the early diagnosis of diabetes. Herein, we utilized advanced composite materials based on nanoporous CuO, CuO/Ag, and CuO/Ag/NiO for glucose detection. The crystalline structure and surface morphology of the synthesized materials were ascertained via powder X-ray diffraction (P-XRD), energy dispersive X-ray (EDX) spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis. The electro-catalytic properties of the manufactured electrode materials for glucose electro-oxidation in alkaline conditions were probed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Notably, the CuO/Ag/NiO electrode material exhibited exceptional performance as a non-enzymatic glucose sensor, displaying a linear range of 0.001–5.50 mM, an ultrahigh sensitivity of 2895.3 μA mM−1 cm−2, and a low detection limit of 0.1 μM. These results suggest that nanoporous CuO/Ag/NiO-based composite materials are a promising candidate for early diagnosis of hyperglycemia and treatment of diabetes. Furthermore, non-enzymatic glucose sensors may pave the way for novel glucometer markets. [ABSTRACT FROM AUTHOR]

Several chemicals, such as dextran sulfate sodium (DSS), oxazolone, acetic acid, and trinitrobenzene sulphonic acid (TNBS), have been used for establishing animal models of ulcerative colitis. These animal models help us to study or explore several factors involved in the etiology or pathogenesis of ulcerative colitis. They are also useful tools to design and develop effective drug delivery strategies. DSS is the most widely used tool to induce colitis in animals. The model of ulcerative colitis developed by this method effectively mimics the colitis condition in humans. The amount of DSS in drinking water can be adjusted to control the severity of colitis, such as acute or chronic inflammation. However, a miscalculation in the amount of DSS produces severe inflammation, which may lead to the death of mice. DSS has been shown to rupture the epithelial lining and induce infiltration of inflammatory markers such as TNF, interferons, and interleukins. The current study aims to study the effects of different amounts of DSS on weight loss, changes in colon length, and histological scoring. Furthermore, the main objective of this study was to find an optimum concentration of DSS to establish a mouse model for ulcerative colitis. Based on the disease index, weight loss, bleeding, histological studies, and colon length, 2.5% w/v DSS for 7 days in water was found to be adequate for the DSS-induced colitis model for a moderate level of colitis, and 3.5% w/v DSS could be used to study severe experimental colitis. [ABSTRACT FROM AUTHOR]

Physiological barrier function is very difficult to replicate in vitro. This situation leads to poor prediction of candidate drugs in the drug development process due to the lack of preclinical modelling for intestinal function. By using 3D bioprinting, we generated a colitis-like condition model that can evaluate the barrier function of albumin nanoencapsulated anti-inflammatory drugs. Histological characterization demonstrated the manifestation of the disease in 3D-bioprinted Caco-2 and HT-29 constructs. A comparison of proliferation rates in 2D monolayer and 3D-bioprinted models was also carried out. This model is compatible with currently available preclinical assays and can be implemented as an effective tool for efficacy and toxicity prediction in drug development. [ABSTRACT FROM AUTHOR]

Ran is a member of the Ras superfamily of proteins, which primarily regulates nucleocytoplasmic trafficking and mediates mitosis by regulating spindle formation and nuclear envelope (NE) reassembly. Therefore, Ran is an integral cell fate determinant. It has been demonstrated that aberrant Ran expression in cancer is a result of upstream dysregulation of the expression of various factors, such as osteopontin (OPN), and aberrant activation of various signaling pathways, including the extracellular-regulated kinase/mitogen-activated protein kinase (ERK/MEK) and phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) pathways. In vitro, Ran overexpression has severe effects on the cell phenotype, altering proliferation, adhesion, colony density, and invasion. Therefore, Ran overexpression has been identified in numerous types of cancer and has been shown to correlate with tumor grade and the degree of metastasis present in various cancers. The increased malignancy and invasiveness have been attributed to multiple mechanisms. Increased dependence on Ran for spindle formation and mitosis is a consequence of the upregulation of these pathways and the ensuing overexpression of Ran, which increases cellular dependence on Ran for survival. This increases the sensitivity of cells to changes in Ran concentration, with ablation being associated with aneuploidy, cell cycle arrest, and ultimately, cell death. It has also been demonstrated that Ran dysregulation influences nucleocytoplasmic transport, leading to transcription factor misallocation. Consequently, patients with tumors that overexpress Ran have been shown to have a higher malignancy rate and a shorter survival time compared to their counterparts. [ABSTRACT FROM AUTHOR]

According to the WHO, as of January 2023, more than 850 million cases and over 6.6 million deaths from COVID-19 have been reported worldwide. Currently, the death rate has been reduced due to the decreased pathogenicity of new SARS-CoV-2 variants, but the major factor in the reduced death rates is the administration of more than 12.8 billion vaccine doses globally. While the COVID-19 vaccines are saving lives, serious side effects have been reported after vaccinations for several premature non-communicable diseases (NCDs). However, the reported adverse events are low in number. The scientific community must investigate the entire spectrum of COVID-19-vaccine-induced complications so that necessary safety measures can be taken, and current vaccines can be re-engineered to avoid or minimize their side effects. We describe in depth severe adverse events for premature metabolic, mental, and neurological disorders; cardiovascular, renal, and autoimmune diseases, and reproductive health issues detected after COVID-19 vaccinations and whether these are causal or incidental. In any case, it has become clear that the benefits of vaccinations outweigh the risks by a large margin. However, pre-existing conditions in vaccinated individuals need to be taken into account in the prevention and treatment of adverse events. [ABSTRACT FROM AUTHOR]

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis. [ABSTRACT FROM AUTHOR]

Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three-dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient-specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient-specific treatment plans and damage site-driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue-engineered skeletal muscle and the peripheral nervous system. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a myeloproliferative haematological malignancy characterized by constitutive activation of BCR-ABL1 tyrosine kinase in the majority of patients. BCR-ABL1 expression activates signaling pathways involved in cell proliferation and survival. Current treatment options for CML include tyrosine kinase inhibitors (TKI) with resistance as a major issue. Various treatment options for overcoming resistance are being investigated. Among them, phytochemical curcumin could play an important role. Curcumin has been found to exhibit anti-cancerous effects in various models, including CML, through regulation of multiple molecular signaling pathways contributing to tumorigenesis. We have evaluated curcumin's effects on imatinib-sensitive LAMA84S and K562, as well as imatinib-resistant LAMA84R cell lines. Our results indicate a significant dose-dependent decrease in cell viability and proliferation of imatinib-sensitive and imatinib-resistant cell lines after curcumin treatment. Suppression of key signaling molecules regulating metabolic and proliferative events, such as Akt, P70S6K and NF-kB, was observed. Increased expression of caspase-3 suggests the potential pro-apoptotic effect of curcumin in the imatinib-resistant CML model. Additional in silico molecular docking studies revealed binding modes and affinities of curcumin with different targets and the results are in accordance with in vitro findings. Altogether, these results indicate the potential role of curcumin in the treatment of CML. [ABSTRACT FROM AUTHOR]

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be −11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability. [ABSTRACT FROM AUTHOR]

Several studies have reported the anti-diabetic effect of biologically synthesized gold nanoparticles (AuNPs). This study was designed to investigate the in vivo anti-diabetic activity of AuNPs synthesized using the leaf extract of Dittrichia viscosa in a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes in rats. AuNPs were synthesized using the leaf extract of D. viscosa, and the synthesized AuNPs were characterized by UV–visible spectrophotometer, dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). To study the anti-hyperglycemic effect of the AuNPs formed using D. viscosa extract, adult male Sprague–Dawley rats were divided into three groups (6–8 rats/group) as follows: control group, a diabetic group without treatment, and a diabetic group treated intraperitoneally with a daily injection of AuNPs at a dose of 2.5 mg/kg for 21 days. Diabetes was induced by maintaining the rats on HFD for 2 weeks, followed by a single intraperitoneal injection of 45 mg/kg of STZ. Serum and liver samples were collected at the end of the treatment period and used to measure glucose levels and hepatic gene expression and activity of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in the liver gluconeogenic pathway. The AuNPs formed using D. viscosa extract were mainly spherical with a size range between 20 and 50 nm with good stability and dispersity, as indicated by the zeta potential and DLS measurements. Treatment with AuNP significantly lowered the blood glucose level, the gene expression, and the activity of hepatic PEPCK in comparison to the diabetic untreated group (P < 0.05). This study suggests that AuNPs synthesized using D. viscosa leaf extract can alleviate hyperglycemia in HFD/STZ-induced diabetes in rats, which could be through the reduction of hepatic gluconeogenesis by inhibiting the expression and activity of the hepatic PEPCK gene. Schematic illustration of the biosynthesis of AuNPs showing their distinctive morphology under the EM. The generated particles were injected into animals and serum glucose levels were reported in addition to the PEPCK expression and activity [ABSTRACT FROM AUTHOR]

When DNA repair is inadequate it increases the chances of the genome becoming unstable and it undergoes a malignant mutation. The deficiency of DNA repair PARP proteins may be leveraged for cancer therapy by increasing genomic instability and causing massive DNA damage in cancer cells. DNA repair components are under increased demand in cancer cells because of the continuous replication of DNA. The oncogenic loss of BRCA and an inefficient DNA repair led to cancer cells being dependent on particular DNA repair pathways, like the Poly (ADP-ribose) polymerase pathway. Breast cancer gene 1 and 2 plays a crucial role in DNA repair and genome integrity explaining how BRCA1 and BRCA2 mutations raise the menace of cancer. PARP inhibitors inhibit the base exclusion repair pathway, resulting in the buildup of unrepaired single strand breaks, which cause inflated replication forks in the S phase and subsequently the development of damaging double stranded breaks. Cells having BRCA mutations are unable to repair DNA breaks, leading to apoptosis and eventually death of cancer cells. Numerous indicators, such as a lack of homologous recombination and a high degree of replication pressure, indicate that this therapy will be very effective. Combining PARP inhibitors with chemotherapy, an immune checkpoint inhibitor, and a targeted drug is an effective strategy for combating PARP inhibitors resistance. Several PARP-based combination approaches are in preclinical and clinical development. Various clinical trials are successfully completed and some are undergoing to evaluate the efficacy of these molecules. This review will describe the current views and clinical updates on PARP inhibitors. [ABSTRACT FROM AUTHOR]

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index < 0.7), nano-range (~357.4 ± 2% nm), transmittance (> 90%), and negative zeta potential (−1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris. [ABSTRACT FROM AUTHOR]