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Omima Mohammed Ali Omima Mohammed,1 Omaima Abdel Majeed Mohamed Salih,2 Islamia Ibrahim Ahmed Omer,3 Yousra Ibrahim Abdallah Mohammed,4 Omer A Mohammed,4 Ammar Elgadi,4 Lina Hemmeda,4 Walaa Elnaiem,4 Malaz Tarig Abdalla Mohamed,4 Areeba Ahsan,5 Khabab Abbasher Hussien Mohamed Ahmed4 1Department of Pediatrics and Child Health, Mohamed Alamin Hamid Tertiary Pediatric Hospital, Omdurman, Sudan; 2Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Omdurman Islamic University, Omdurman, Sudan; 3Pediatrics and Child Health Department, College of Medicine, Sulaiman Al Rajhi University, Al-Bukayriyah, Qassim Province, Saudi Arabia; 4Faculty of Medicine, University of Khartoum, Khartoum, Sudan; 5School of Health Sciences, Foundation University, Islamabad, PakistanCorrespondence: Khabab Abbasher Hussien Mohamed Ahmed, Email khabab9722@gmail.comBackground: Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13– 16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients’ specific treatment.Objective: To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma.Methodology: This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant.Results: In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype.Conclusion: This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.Keywords: asthma, pediatrics, respiratory system, chronic obstructive pulmonary diseases, Sudan

Reham Fattoh,1 Amr Mounir,2 Mohamed Anbar,2 Osama Ali Mohammed2 1Ophthalmology Department, Sohag Ophthalmology Hospital, Sohag, Egypt; 2Ophthalmology Department, Sohag Faculty of Medicine, Sohag University, Sohag, EgyptCorrespondence: Amr Mounir, Ophthalmology Department, Sohag Faculty of Medicine, Sohag University, Almohafza Street, Mailbox: 8251, Sohag, Egypt, Tel +20 1005026170, Email dramrmonir@yahoo.comPurpose: The study aimed to determine changes detected by noncontact meibography and noninvasive break-up time test (NIBUT) in individuals with regular use of soft contact lenses and compare these findings with irregular soft contact lenses wearers who not compliant with them and non-wearers control group.Patients and Methods: A prospective nonrandomized case-control study in which individuals were recruited and distributed into three groups: Group A (regular contact lens wearers), group B (irregular contact lens wearers), and group C (non-wearers). Ocular Surface Disease Index (OSDI) was obtained. Noncontact meibography and noninvasive tear break-up time were measured without lenses on using Sirius® Scheimpflug Camera.Results: One hundred sixty-six eyes of 83 individuals were included; 36 eyes in group A, 50 eyes in group B, and 80 eyes in group C. The mean total meiboscore was 1.99, 1.61, and 1.28, respectively. The mean meibograde was 3.03, 2.86, and 1.99, respectively. Noninvasive break-up time (NIF-BUT) was 8.42, 11.76, and 13.57 seconds, respectively.Conclusion: There is a difference in OSDI score, meibomian score, and break-up time between different study groups. The study results show that there are trends in lens wearers and non-lens wearers. This is useful for the field to understand the differences between lens wearers and non-lens wearers.Keywords: noncontact meibography, noninvasive break-up time, soft contact lenses

Caseous mitral annular calcification (CMAC), sometimes called liquefaction necrosis of mitral annular calcification (MAC), is a rare variant of MAC, a chronic degenerative process that progresses with age. It is a degenerative abnormality of the fibrous tissue and typically involves the posterior annulus, appearing as a smooth mass with no flow or acoustic shadow artefacts. It can be differentiated from other cardiac masses by CT and MRI. Whilst benign in nature, it is associated with a range of pathologies, such as mitral valve dysfunction, arrhythmias, and systemic embolisation. Given the risk of systemic embolisation, surgery may be appropriate, but there is no clear consensus in the literature in patients who are asymptomatic. This case highlights a case of CMAC presenting with a retinal artery occlusion, and was managed conservatively. Background The mitral annulus is a key component of the mitral valve, ensuring appropriate function by facilitating complete closure of the leaflets during systole. With age, MAC can occur, potentially resulting in mitral valve dysfunction, infective endocarditis, and arrhythmias. CMAC is a rare variant of MAC, typically involving the posterior annulus. Whilst benign, the risk of complications, such as systemic embolisation, may indicate a surgical approach to management, even in patients who are asymptomatic. Case Presentation A 60-year-old female, presenting with sudden loss of vision in the lower part of her left eye due to a branch retinal artery embolus, was admitted from ophthalmology services. An outpatient transthoracic echocardiogram showed an abnormal mass on the posterior annulus of the mitral valve. Transoesophageal echocardiography identified a calcified posterior aspect of the mitral annulus with normal leaflet mobility and trivial regurgitation, and an echogenic mass attached to the ventricular aspect of the mitral annulus (at the level of posteromedial commissure), 9x4 mm in size. A cardiac CT showed a caseous mitral valve with evidence of rupture of the calcified shell. Discussion with the surgical multidisciplinary team resulted in a conservative approach, with follow-up echo for monitoring. Conclusion Whilst a benign and rare variant of MAC, CMAC is associated with a range of pathologies, including mitral valve disease, arrhythmias, and systemic embolisation. Currently, there is no standardised management approach for CMAC. Surgery is currently recommended in the context of already known surgically indicated pathologies, such as severe mitral valve disease or systemic embolisation. However, this conservatively-managed patient has had no further complications with stable echocardiographic appearance on repeat echo 3 months following initial exam.

Abstract The COVID‐19 pandemic has disturbed medical training. Haematology registrars were surveyed using SurveyMonkey. Eighty‐nine out of 269 (24.9%) responded. Reported stressors included concerns about transmitting the infection, disruption of leave, inferior patient outcomes, survivors’ guilt and interruption of career progression. Only 31.2% felt ready to progress to the next training stage. Reported causes of lack of training were disruption of clinics and training days and utilisation of telephone consultations. Several stressors negatively impacted haematology registrars’ well‐being, training and progression. More emphasis on psychological support, outpatient clinic work and e‐learning is needed.

Yohannes Tsegyie Wondmkun,1 Ousman Ahmed Mohammed2 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2College of Health Sciences, Woldia University, Woldia, EthiopiaCorrespondence: Yohannes Tsegyie WondmkunDepartment of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Churchill Avenue, P.O. Box 1176, Addis Ababa, EthiopiaEmail yohannes.tsegyie@aau.edu.etAbstract: Severe acute respiratory syndrome coronavirus-2 causes coronavirus disease-19 (COVID-19) that spreads quickly in the world. Considering the impact of this pandemic, researchers have been racing to understand the peculiar nature of the virus and the pathogenesis of the disease to uncover possible drug targets, effective therapeutic agents, and vaccines. Accordingly, numerous drug targets are identified by scientists. Among them, structural glycoproteins, virulence factors, host-specific receptors and enzymes, non-structure proteins, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, and pro-inflammatory cytokines are discussed herein. This review summarizes the promising drug targets for COVID-19, and highlights antiviral strategies which depend on molecular interactions between viral small molecules and host biologic machinery for repurposing the available clinical drugs. In addition, it gives a strong rational basis for the ongoing discovery of new drugs and vaccines.Keywords: COVID-19, drug targets, SARS-COV-2, non-structural proteins, structural proteins

In this tribological study, we highlight the effect of lubricating oil viscosity in the Multi-pads hydrodynamic journal bearings generate important improvement in characteristics of stiffness and stability in the high speed turbomachines. Depending on viscosity of oil film (three values) variation for five tilted pads bearing, each pad is pivoted and is facilitated to be tilted with small angles, by using Matlab program, we calculate the oil film thickness for convergence layer. We applied Reynold's equation and solved it's numerically by using finite difference method with 5 nodes technique to find the pressure distributed on each node in the mesh of tilted pad, then calculate stiffness coefficients. Results show that there is clear effect on stiffens with viscosity change. The increase in value of Krr (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is14.33 MN/m, while the increase in Krr value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is 11.37 MN/m. the increase in value the of Kss (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is5.921 MN/m, while increase in Kss value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is9.55 MN/m respectively. the increase in value of Ksr (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is 8.95 MN/m, while the increase in Ksr value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is 14.41 MN/m respectively. the increase in value of Krs (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) are 5.08 MN/m, while the increase in Krs value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is8.19 MN/m respectively. The values of the dominate principal coefficients Krr is greater than that of Ksr, also The values of the principal coefficients Kss is greater than that of cross coupling Krs for all values of viscosity that studied. From this result, we can conclude the side effect of cross coupling coefficients (Ksr ,Krs) can be overcome by great values for principal coefficient (Krr, Kss) respectively, so we can get good improvement instability for this bearing by variation the viscosity. After that, we regarded to use high viscosity lubricant in multi-pad journal bearing to improve the performance and stability by controlling the stiffness coefficients.

In this tribological study, we highlight the effect of lubricating oil viscosity in the Multi-pads hydrodynamic journal bearings generate important improvement in characteristics of stiffness and stability in the high speed turbomachines. Depending on viscosity of oil film (three values) variation for five tilted pads bearing, each pad is pivoted and is facilitated to be tilted with small angles, by using Matlab program, we calculate the oil film thickness for convergence layer. We applied Reynold’s equation and solved it’s numerically by using finite difference method with 5 nodes technique to find the pressure distributed on each node in the mesh of tilted pad, then calculate stiffness coefficients. Results show that there is clear effect on stiffens with viscosity change. The increase in value of Krr (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is14.33 MN/m, while the increase in Krr value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is 11.37 MN/m. the increase in value the of Kss (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is5.921 MN/m, while increase in Kss value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is9.55 MN/m respectively. the increase in value of Ksr (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) is 8.95 MN/m, while the increase in Ksr value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is 14.41 MN/m respectively. the increase in value of Krs (for n = 0.3) between viscosity (0.04 Pas. s) and viscosity (0.058 Pas. s) are 5.08 MN/m, while the increase in Krs value between viscosity (0.058 Pas. s) and viscosity (0.087 Pas. s) is8.19 MN/m respectively. The values of the dominate principal coefficients Krr is greater than that of Ksr, also The values of the principal coefficients Kss is greater than that of cross coupling Krs for all values of viscosity that studied. From this result, we can conclude the side effect of cross coupling coefficients (Ksr ,Krs) can be overcome by great values for principal coefficient (Krr, Kss) respectively, so we can get good improvement instability for this bearing by variation the viscosity. After that, we regarded to use high viscosity lubricant in multi-pad journal bearing to improve the performance and stability by controlling the stiffness coefficients.

Gouty arthritis is a prevalent inflammatory illness. Gout attacks begin when there is an imbalance in the body's uric acid metabolism, which leads to urate buildup and the development of the ailment. A family of conserved, short non-coding RNAs known as microRNAs (miRNAs) can regulate post-transcriptional protein synthesis by attaching to the 3' untranslated region (UTR) of messenger RNA (mRNA). An increasing amount of research is pointing to miRNAs as potential players in several inflammatory diseases, including gouty arthritis. miRNAs may influence the progression of the disease by regulating immune function and inflammatory responses. This review mainly focused on miRNAs and how they contribute to gouty arthritis. It also looked at how miRNAs could be used as diagnostic, prognostic, and potential therapeutic targets., Competing Interests: Declarations Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Infertility is a multifactorial reproductive system disorder, and most infertility cases occur in men. Semen testing is now thought to be the most important diagnostic test for infertile men; nonetheless, because of its limitations, the cause of infertility remains unknown for 40% of infertile men. Semen assessment's shortcomings indicate the need for improved and innovative diagnostic techniques and biomarkers worldwide. Non-coding RNAs with a length of roughly 18-22 nucleotides are called microRNAs (miRNAs). Most of our protein-coding genes are post-transcriptionally regulated by them. These molecules are unusual in bodily fluids, and aberrant variations in their expression can point to specific conditions like infertility. As a result, fresh potential biomarkers for the diagnosis and prognosis of various forms of male infertility may be represented by miRNAs. This review examined the most recent research revealing the association between different miRNAs' functions in male infertility and their expression patterns. Also, it aims to figure out the most recent strategies that could be applied for using such miRNAs as possible therapeutic targets for infertility treatment., Competing Interests: Declarations Ethical approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer's complexity and heterogeneity continue to present significant challenges in its treatment and management. Emerging research has underscored the pivotal role of microRNAs (miRNAs) in breast cancer pathogenesis, acting as crucial regulators of gene expression. This review delivers an in-depth analysis of miRNAs, highlighting their dual functions as both oncogenes and tumor suppressors, and detailing their impact on key biological processes, including cell proliferation, apoptosis, and metastasis. The mechanisms underlying miRNA action, particularly their interactions with target mRNAs and the factors influencing these dynamics, are thoroughly explored. Additionally, the review discusses the therapeutic prospects of miRNAs, with a focus on innovative delivery systems like nanoparticles that improve the stability and effectiveness of miRNA-based therapies. It also addresses the anticancer effects of natural compounds, such as genistein, hesperidin, quercetin, curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), and glyceollins, which modulate miRNA expression and contribute to tumor growth inhibition. These advances seek to address the limitations of conventional therapies, paving the way for targeted interventions in breast cancer. By integrating current insights on miRNA biology, therapeutic strategies, and the potential of natural products to regulate miRNA expression, this review aims to shed light on miRNA- and natural product-based approaches as promising avenues for enhancing breast cancer treatment outcomes., Competing Interests: Declarations Ethics approval and consent to participate Not Applicable. Human and animal ethics Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements., 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. The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lipid nanoparticles (LNPs) have emerged as transformative tools in modern drug delivery, offering unparalleled potential in enhancing the efficacy and safety of various therapeutics. In the context of rheumatoid arthritis (RA), a disabling autoimmune disorder characterized by chronic inflammation, joint damage, and limited patient mobility, LNPs hold significant promise for revolutionizing treatment strategies. LNPs offer several advantages over traditional drug delivery systems, including improved pharmacokinetics, enhanced tissue penetration, and reduced systemic toxicity. This article concisely summarizes the pathogenesis of RA, its associated risk factors, and therapeutic techniques and their challenges. Additionally, it highlights the noteworthy advancements made in managing RA through LNPs, including liposomes, niosomes, bilosomes, cubosomes, spanlastics, ethosomes, solid lipid nanoparticles, lipid micelles, lipid nanocapsules, nanostructured lipid carriers, etc . It also delves into the specific functional attributes of these nanocarrier systems, focusing on their role in treating and monitoring RA.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mohammed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Psoriasis is a sustainable skin disease characterized by inflammation resulting from the interaction between immune cells and keratinocytes. Significant advancements have been achieved in studying the molecular process behind noncoding and coding genes, leading to valuable insights for clinical therapy. Nevertheless, our comprehension of this intricate ailment remains ambiguous. Natural products such as curcumin, vitamin D, omega-3, vitamin E, psoralen, gallic acid (GA), and resveratrol offer a promising alternative or adjunct therapy for psoriasis by modulating multiple pathways and exhibiting fewer side effects compared to conventional treatments. MicroRNAs (miRNAs) are short RNAs that are involved in regulating gene expression after transcription, namely by suppressing gene activity. Recent research on miRNAs has uncovered their significant significance in the development of psoriasis. In this review, we examined the latest developments in the investigation of miRNAs in psoriasis. Previous studies have revealed that imbalanced miRNAs in psoriasis have a significant impact on the processes of keratinocyte differentiation, proliferation, and the progression of inflammation. Furthermore, miRNAs exert an impact on the activity of immune cells involved in psoriasis, such as Langerhans cells, dendritic cells, and CD4 + T cells. Furthermore, we explore potential miRNA-focused treatment options for psoriasis, including the localized administration of external miRNA mimics, and miRNA inhibitors. The effectiveness of natural products and miRNAs in treating psoriasis, as well as the signaling pathways that may be involved, are summarized in this article., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a leading liver cancer that significantly impacts global life expectancy and remains challenging to treat due to often late diagnoses. Despite advances in treatment, the prognosis is still poor, especially in advanced stages. Studies have pointed out that investigations into the molecular mechanisms underlying HCC, including mitochondrial dysfunction and epigenetic regulators, are potentially important targets for diagnosis and therapy. Mitoepigenetics, or the epigenetic modifications of mitochondrial DNA, have drawn wide attention for their role in HCC progression. Besides, molecular biomarkers such as mitochondrial DNA alterations and non-coding RNAs showed early diagnosis and prognosis potential. Additionally, natural compounds like alkaloids, resveratrol, curcumin, and flavonoids show promise in HCC show promise in modulating mitochondrial and epigenetic pathways involved in cancer-related processes. This review discusses how mitochondrial dysfunction and epigenetic modifications, especially mitoepigenetics, influence HCC and delves into the potential of natural products as new adjuvant treatments against HCC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oral cancer (OC) is a significant global health issue, with high rates of both mortality and morbidity. Conventional treatments, including surgery, radiation, and chemotherapy, are commonly used, but they often come with serious side effects and may not fully eliminate cancer cells, resulting in recurrence and resistance to treatment. In recent years, natural products derived from plants and other biological sources have gained attention for their potential anticancer properties. These compounds offer advantages such as lower toxicity compared to traditional chemotherapy. Notable natural compounds like quercetin, berberine, curcumin, andrographolide, nimbolide, ovatodiolide, and cucurbitacin B have demonstrated effectiveness in inhibiting OC cell growth by targeting various signaling pathways involved in cancer progression. Recent breakthroughs in molecular biology have highlighted the crucial role of microRNAs (miRNAs) in the development of OC. Targeting dysregulated miRNAs with natural products offers a promising strategy for treating the disease. Natural compounds exert anticancer effects by influencing both altered cellular signaling pathways and miRNA expression profiles. This study aims to explore the role of miRNAs as potential molecular targets in OC and to investigate how natural products may regulate these miRNAs. Additionally, this review will shed light on the therapeutic potential of phytochemicals in modulating miRNA expression and their significance in OC treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The newly discovered programmed iron-dependent necrosis, ferroptosis, is a novel pathway that is controlled by iron-dependent lipid peroxidation and cellular redox changes. It can be triggered intrinsically by low antioxidant enzyme activity or extrinsically by blocking amino acid transporters or activating iron transporters. The induction of ferroptosis involves the activation of specific proteins, suppression of transporters, and increased endoplasmic reticulum (ER) stress (a condition in which the ER, a crucial organelle involved in protein folding and processing, becomes overwhelmed by an accumulation of misfolded or unfolded proteins. This situation disrupts the normal functioning of the ER, leading to a cellular stress response known as the unfolded protein response), leading to lipid peroxidation byproduct accumulation and toxic reactive oxygen species (ROS), which are highly reactive molecules derived from diatomic oxygen and include various forms such as superoxide (O₂⁻), hydroxyl radicals (•OH), and hydrogen peroxide (H₂O₂). Ferroptosis is closely associated with signaling molecules in lung cancer, including epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1-alpha (HIF-1α), and P53, and is regulated by epigenetic factors such as microRNAs (miRNAs). miRNAs are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Several miRNAs have been found to modulate ferroptosis by targeting key genes involved in iron metabolism, lipid peroxidation, and antioxidant defense pathways. The research on ferroptosis has expanded to target its role in lung cancer treatment and resistance prevention. This review encapsulates the significance of ferroptosis in lung cancer. Understanding the mechanisms and implications of ferroptosis in lung cancer cells may lead to targeted therapies exploiting cancer cell vulnerabilities to ferroptosis Also, improving treatment outcomes, and overcoming resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Behçet's Disease (BD) is an intricate medical puzzle, captivating researchers with its enigmatic pathogenesis. This complex ailment, distinguished by recurrent mouth and genital lesions, eye irritation, and skin injuries, presents a substantial obstacle to therapeutic research. This review explores the complex interaction of microRNAs (miRNAs) with BD, highlighting their crucial involvement in the disease's pathophysiology. miRNAs, recognized for regulatory influence in diverse biological processes, hold a pivotal position in the molecular mechanisms of autoimmune diseases, such as BD. The exploration begins with examining miRNA biogenic pathways and functions, establishing a foundational understanding of their regulatory mechanisms. Shifting to the molecular landscape governing BD, the review highlights miRNA-mediated impacts on critical signaling pathways like Notch, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protein kinase B (AKT)/mammalian target of rapamycin (mTOR), offering insights into intricate pathophysiological mechanisms. Dissecting the immunological landscape reveals the profound influence of miRNAs on BD, shedding light on the intricate modulation of immune responses and offering novel perspectives on disease etiology and progression. Beyond molecular intricacies, the review explores the clinical relevance of miRNAs in BD, emphasizing their potential as diagnostic and prognostic indicators. The discussion extends to the promising realm of miRNA-based therapeutic interventions, highlighting their potential in alleviating symptoms and altering disease progression. This comprehensive review, serving as a valuable resource for researchers, clinicians, and stakeholders, aims to decipher the intricate molecular tapestry of BD and explore the therapeutic potential of miRNAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gastric cancer (GC) remains a major public health challenge worldwide. Long non-coding RNAs (lncRNAs) play important roles in the development, progression, and resistance to the treatment of GC, as shown by recent developments in molecular characterization. Still, an in-depth investigation of the lncRNA landscape in GC is absent. However, The objective of this systematic review is to evaluate our present understanding of the role that lncRNA dysregulation plays in the etiology of GC and treatment resistance, with a focus on the underlying mechanisms and clinical implications. Research that described the functions of lncRNA in angiogenesis, stemness, epigenetics, metastasis, apoptosis, development, and resistance to key treatments was given priority. In GC, it has been discovered that a large number of lncRNAs, including MALAT1, HOTAIR, H19, and ANRIL, are aberrantly expressed and are connected with disease-related outcomes. Through various methods such as chromatin remodeling, signal transduction pathways, and microRNA sponging, they modulate hallmark cancer capabilities. Through the activation of stemness programs, epithelial-mesenchymal transition (EMT), and survival signaling, LncRNAs also control resistance to immunotherapy, chemotherapy, and targeted therapies. By clarifying their molecular roles further, we may be able to identify new treatment targets and ways to overcome resistance. This article aims to explore the interplay between lncRNAs, and GC. Specifically, the focus is on understanding how lncRNAs contribute to the etiology of GC and influence treatment resistance in patients with this disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/β-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases., Recent Findings: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study reports the comparative evaluation of yield, physico-chemical composition and biological attributes (antioxidant activity, antimicrobial activity, biofilm inhibition and hemolytic activity) of peppermint ( Mentha piperita L.) essential oil (EO) obtained by hydro-distillation (HD) and supercritical fluid (CO 2 ) extraction (SCFE) methods. The yield (%) of EO obtained by HD (0.20 %) was significantly ( p  < 0.05) higher than that of SCFE (0.13 %) while the variation in the physical parameters like solubility, color, density (at 25 °C) and refractive index (at 25 °C) was not significant between the tested oils. The data of chemical compositional analysis revealed that menthol was the key component in the EO obtained by HD (52.85 %) and SCFE (45.51 %), followed by menthone [HD (25.93 %) and SCFE (27.3 %)] and eucalyptol [HD (8.59 %); SCFE (8.92 %)]. The EO extracted with supercritical fluid (SCFE-EO) exhibited superior ( p  < 0.05) DPPH free radical inhibition potential (52 %) with an IC 50 value of 15.65 μg/mL and reducing power compared to that of HD-EO. The highest antimicrobial activity was exhibited by SCFE-EO against Pasturella multocida with an inhibition zone of 18.00 mm (MIC value of 86 μg/mL). The results of biofilm inhibition and hemolytic activity revealed that the SCFE method was superior to recover high quality EO in comparison to the HD method. The peppermint EO obtained by SCFE, owing to potent bioactive components, can be a potential candidate to develop nutra-pharmaceuticals., 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.)

Dorstenia psilurus is a widely used plant spice in traditional African medicine to treat pain-related conditions. However, the anti-inflammatory mechanisms underlying this activity and the main active ingredients of D. psilurus have not yet been fully characterized. This study aimed to isolate and identify the main active anti-inflammatory constituents of the D. psilurus extract and to investigate the underlying anti-inflammatory mechanisms in murine macrophages. Chromatographic techniques and spectroscopic data were used for compound isolation and structure elucidation. The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and 15-lipoxygenase activity, respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit, and Th1/Th2 cytokine measurement was performed using a flow cytometer. The results indicated that the extract and fractions of D. psilurus inhibit NO production and proliferation of RAW 264.7 macrophage cells. Bioguided fractionation led to the identification of psoralen, a furocoumarin, as the main bioactive anti-inflammatory compound. Psoralen inhibited NO production and 15-lipoxygenase activity and reduced pro-inflammatory Th1 cytokines (IFN- γ , TNF- α , and IL-2) while increasing the secretion of anti-inflammatory cytokines (IL-4, IL-6, and IL-10) in activated RAW 264.7 macrophage cells. The encouraging results obtained in this study suggest that psoralen-based multiple modulation strategies could be a useful approach to address the treatment of inflammatory diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Adamu Imam Isa et al.)

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-β, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone ( 1 ), smeathxanthone A ( 2 ), smeathxanthone B ( 3 ), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone ( 4 ); and three benzophenones guttiferone O ( 5 ), guttiferone M ( 6 ), and aristophenone A ( 7 ) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound ( 6 ), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound ( 5 ) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone ( 1 ), guttiferone O ( 5 ), and guttiferone ( 6 ) as potential candidates for the development of anti-inflammatory drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeelani, Fouotsa, Mohammed, Alfaifi, Adebayo, Ahmed, Yahia, Eissa, Bahashwan, Mohammed, Alotaibi, Asiri, Rezigallah, Alharthi, Dzoyem and Isa.)

Background: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC., Objective: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker., Materials and Methods: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR., Results: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%)., Conclusion: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Golam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epigenetic processes, including non-coding RNA, histone modifications, and DNA methylation, play a vital role in connecting the environment to the development of a disorder, especially when there is a favorable genetic background. Ankylosing Spondylitis (AS) is a chronic type of spinal arthritis that highlights the significance of epigenetics in diseases related to autoimmunity and inflammation. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in both normal and aberrant pathological and physiological gene expression. This study focuses on the pathophysiological pathways to clarify the role of miRNAs in AS. We have conducted a thorough investigation of the involvement of miRNAs in several processes, including inflammation, the production of new bone, T-cell activity, and the regulation of pathways such as BMP, Wnt, and TGFβ signaling. Undoubtedly, miRNAs play a crucial role in enhancing our comprehension of the pathophysiology of AS, and their promise as a therapeutic strategy is quickly expanding., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body β-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases β-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous β-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of β-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous β-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma β-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma β-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The present research examined patulin's presence across the whole supply chain of selected fruits. A comprehensive analysis was conducted on 442 samples of fruits (oranges, apples, apricots, lemons, and guava) to determine the presence of patulin contamination. This analysis used Liquid Chromatography (HPLC) with a UV detector. The findings indicate that 17, 23, and 28 % of selected fruit samples tested positive for patulin levels in farm, transportation, and market samples. However, the sample collected during the transportation step showed that 56 % (percentage of positive samples) of fruits have patulin levels greater than 50 μg/kg, and 41 % (percentage of positive samples) have greater levels than 50 μg/kg in market samples. The findings of the one-way analysis of variance indicated that no statistically significant variation existed between the amounts of patulin across the various stages of the food supply chain system (p > 0.05). Nevertheless, the analysis of the correlation study, namely Kendall's tau&#95;b and Spearman's rho, denote a robust association between the levels of patulin and the food supply system. The apple samples exhibited the most significant average dietary intake of patulin, with an average value of 0.11 μg/kg bw/day. The maximum mean hazard quotient (HQ) of 0.28 was also recorded. The prevalence and incidence of patulin in specific fruits were found to be relatively high, and it was observed that market samples had elevated levels of patulin in the selected fruits., 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.)

Background: Distractor efficiency (DE) of multiple-choice questions (MCQs) responses is a component of the psychometric analysis used by the examiners to evaluate the distractors' credibility and functionality. This study was conducted to evaluate the impact of the DE on the difficulty and discrimination indices., Methods: This cross-sectional study was conducted from April to June 2023. It utilizes the final exam of the Principles of Diseases Course with 45 s-year students. The exam consisted of 60 type A MCQs. Item analysis (IA) was generated to evaluate KR20, difficulty index (DIF), discrimination index (DIS), and distractor efficiency (DE). DIF was calculated as the percentage of examinees who scored the item correctly. DIS is an item's ability to discriminate between higher and lower 27% of examinees. For DE, any distractor selected by less than 5% is considered nonfunctional, and items were classified according to the non-functional distractors. The correlation and significance of variance between DIF, DI, and DE were evaluated., Results: The total number of examinees was 45. The KR-20 of the exam was 0.91. The mean (M), and standard deviation (SD) of the DIF of the exam was 37.5(19.1), and the majority (69.5%) were of acceptable difficulty. The M (SD) of the DIS was 0.46 (0.22), which is excellent. Most items were excellent in discrimination (69.5%), only two were not discriminating (13.6%), and the rest were of acceptable power (16.9%). Items with excellent and good efficiency represent 37.3% each, while only 3.4% were of poor efficiency. The correlation between DE and DIF (p = 0.000, r= -0.548) indicates that items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and vice versa. The correlation between DE and DIS is significantly negative (P = 0.0476, r=-0.259). In such a correlation, items with efficient distractors are associated with low-discriminating items., Conclusions: There is a significant moderate negative correlation between DE and DIF (P = 0.00, r = -0.548) and a significant weak negative correlation between DE and DIS (P = 0.0476, r = -0.259). DIF has a non-significant negative correlation with DIS (P = 0.7124, r = -0.0492). DE impacts both DIF and DIS. Items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and discriminating items. Improving the quality of DE will decrease the number of NFDs and result in items with acceptable levels of difficulty index and discrimination power., (© 2024. The Author(s).)

Ceftriaxone sodium belongs to the third-generation cephalosporin group and is used intramuscular and intravenous route as a broad-spectrum antibiotic. This research aims to prepare biocompatible hydrogels for targeted delivery of ceftriaxone sodium by parental route. Different proportions of polymers (natural and synthetic) in the presence of cross-linker were synthesized by solvent casting method. Ceftriaxone sodium was loaded in hydrogels in different concentrations and its drug release behavior was evaluated along with swelling and biodegradation analysis. The characterization of hydrogel was done by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) to analyze surface morphology and functional groups involved in the formation of dextrin/Na-alginate/PVA hydrogels loaded with the drug. Thermogravimetric analysis (TGA) was confirmed by thermal stability and degradation pattern of loaded and unloaded hydrogels. The drug-loaded samples presented promising antimicrobial activity against S. aureus and P. multocida and their cytotoxic nature was also studied. Drug release analysis using simulated intestinal fluid (SIF) and phosphate buffer saline(PBS) for the circulatory system shows the consistent release of the drug. The findings unveiled the development of a biocompatible and innovative hydrogel, which has potential advantages for biomedical application, particularly in enhancing the therapeutic efficacy of ceftriaxone sodium drug., 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.)

Gallbladder cancer (GBC) is one of the most aggressive types of biliary tree cancers and the commonest despite its rarity. It is infrequently diagnosed at an early stage, further contributing to its poor prognosis and low survival rate. The lethal nature of the disease has underlined a crucial need to discern the underlying mechanisms of GBC carcinogenesis which are still largely unknown. However, with the continual evolution in the research of cancer biology and molecular genetics, studies have found that non-coding RNAs (ncRNAs) play an active role in the molecular pathophysiology of GBC development. Dysregulated long non-coding RNAs (lncRNAs) and their interaction with intracellular signaling pathways contribute to malignancy and disease development. LncRNAs, a subclass of ncRNAs with over 200 nucleotides, regulate gene expression at transcriptional, translational, and post-translational levels and especially as epigenetic modulators. Thus, their expression abnormalities have been linked to malignancy and therapeutic resistance. lnsRNAs have also been found in GBC patients' serum and tumor tissue biopsies, highlighting their potential as novel biomarkers and for targeted therapy. This review will examine the growing involvement of lncRNAs in GBC pathophysiology, including related signaling pathways and their wider clinical use., 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.)

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

MicroRNAs (miRNAs) are short RNA molecules that are not involved in coding for proteins. They have a significant function in regulating gene expression after the process of transcription. Their participation in several biological processes has rendered them appealing subjects for investigating age-related disorders. Increasing data indicates that miRNAs can be influenced by dietary variables, such as macronutrients, micronutrients, trace minerals, and nutraceuticals. This review examines the influence of dietary factors and nutraceuticals on the regulation of miRNA in relation to the process of aging. We examine the present comprehension of miRNA disruption in age-related illnesses and emphasize the possibility of dietary manipulation as a means of prevention or treatment. Consolidating animal and human research is essential to validate the significance of dietary miRNA control in living organisms, despite the abundance of information already provided by several studies. This review elucidates the complex interaction among miRNAs, nutrition, and aging, offering valuable insights into promising areas for further research and potential therapies for age-related disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Salama, Eissa, Doghish, Abulsoud, Abdelmaksoud, Mohammed, Abdel Mageed and Darwish.)

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma., Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs., Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma., 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.)

Currently, there are no viable curative treatments that can enhance the central nervous system's (CNS) recovery from trauma or illness. Bioengineered injectable smart/stimuli-responsive hydrogels (SSRHs) that mirror the intricacy of the CNS milieu and architecture have been suggested as a way to get around these restrictions in combination with medication and cell therapy. Additionally, the right biophysical and pharmacological stimuli are required to boost meaningful CNS regeneration. Recent research has focused heavily on developing SSRHs as cutting-edge delivery systems that can direct the regeneration of brain tissue. In the present article, we have discussed the pathology of brain injuries, and the applicable strategies employed to regenerate the brain tissues. Moreover, the most promising SSRHs for neural tissue engineering (TE) including alginate (Alg.), hyaluronic acid (HA), chitosan (CH), gelatin, and collagen are used in natural polymer-based hydrogels and thoroughly discussed in this review. The ability of these hydrogels to distribute bioactive substances or cells in response to internal and external stimuli is highlighted with particular attention. In addition, this article provides a summary of the most cutting-edge techniques for CNS recovery employing SSRHs for several neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage., (© 2024 Federation of American Societies for Experimental Biology.)

Epilepsy is a medical condition characterized by intermittent seizures accompanied by changes in consciousness. Epilepsy significantly impairs the daily functioning and overall well-being of affected individuals. Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from various dysfunctions in brain activity. The molecular processes underlying changes in neuronal structure, impaired apoptotic responses in neurons, and disruption of regenerative pathways in glial cells in epilepsy remain unknown. MicroRNAs (miRNAs) play a crucial role in regulating apoptosis, autophagy, oxidative stress, neuroinflammation, and the body's regenerative and immune responses. miRNAs have been shown to influence many pathogenic processes in epilepsy including inflammatory responses, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, and other processes related to the development of epilepsy. Therefore, the purpose of our current analysis was to determine the role of miRNAs in the etiology and progression of epilepsy. Furthermore, they have been examined for their potential application as biomarkers and therapeutic targets., 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. The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options., 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.)

microRNAs (miRNAs) play a crucial role in brain growth and function. Hence, research on miRNA has the potential to reveal much about the etiology of neuropsychiatric diseases. Among these, schizophrenia (SZ) is a highly intricate and destructive neuropsychiatric ailment that has been thoroughly researched in the field of miRNA. Despite being a relatively recent area of study about miRNAs and SZ, this discipline has advanced enough to justify numerous reviews that summarize the findings from the past to the present. However, most reviews cannot cover all research, thus it is necessary to synthesize the large range of publications on this topic systematically and understandably. Consequently, this review aimed to provide evidence that miRNAs play a role in the pathophysiology and progression of SZ. They have also been investigated for their potential use as biomarkers and therapeutic targets., 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.)