Search

Fascin-1 (FSCN1) is recognized as an actin-binding protein, commonly exhibits up-regulation in breast cancer (BC) and is crucial for tumor invasion and metastasis. The existence of FSCN1 gene polymorphisms may raise the potential for developing BC, and there are still no studies focusing on the relationship between the FSCN1 rs2966447 variant and BC risk in Egyptian females. Thus, we investigated the serum fascin-1 levels in BC patients and the association between the FSCN1 rs2966447 variant with its serum levels and BC susceptibility. Genotyping was conducted in 153 treatment-naïve BC females with different stages and 144 apparent healthy females by TaqMan® allelic discrimination assay, whereas serum fascin-1 level quantification was employed by ELISA. The FSCN1 rs2966447 variant demonstrated a significant association with BC susceptibility under all utilized genetic models, cancer stages and estrogen receptor negativity. Also, BC females with AT and TT genotypes had higher serum fascin-1 levels and tumor size than those with the AA genotype. Moreover, serum fascin-1 levels were significantly elevated in the BC females, notably in those with advanced-stages. Furthermore, serum fascin-1 levels were markedly positively correlated with number of positive lymph nodes as well as tumor size. Collectively, these findings revealed that the FSCN1 rs2966447 variant may be regarded as a strong candidate for BC susceptibility. Also, this intronic variant is associated with increased serum fascin-1 levels and tumor size., 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.)

Purpose: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC., Methods: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay., Results: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk., Conclusions: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC., (© 2024. The Author(s).)

Breast cancer (BC) is the most common type of cancer in women to be diagnosed, and it is also the second leading cause of cancer death in women globally. It is the disease that causes the most life years adjusted for disability lost among women, making it a serious worldwide health issue. Understanding and interpreting carcinogenesis and metastatic pathways is critical for curing malignancy. Fascin-1 was recognized as an actin-bundling protein with parallel, rigid bundles as a result of the cross-linking of F-actin microfilaments. Increasing levels of fascin-1 have been associated with bad prognostic profiles, aggressiveness of clinical courses, and poor survival outcomes in a variety of human malignancies. Cancer cells that overexpress fascin-1 have higher capabilities for proliferation, invasion, migration, and metastasis. Fascin-1 is being considered as a potential target for therapy as well as a potential biomarker for diagnostics in a variety of cancer types. This review aims to provide an overview of the FSCN1 gene and its protein structure, elucidate its physiological and pathological roles, and throw light on its involvement in the initiation, development, and chemotherapeutic resistance of BC., 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.)

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies., 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 © 2023 Elsevier GmbH. All rights reserved.)

Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/β-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions., 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 © 2023 Elsevier GmbH. All rights reserved.)

Women of reproductive age are frequently affected by the heterogeneous endocrine-metabolic conditions recognized as polycystic ovarian syndrome (PCOS). Moreover, FSH (Follicle-stimulating hormone), steroidogenesis, and LH (Luteinizing Hormone) are suppressed by the anti-Mullerian hormone, a good indicator of ovarian reserve, that is generated from granulosa cells. In the past ten years, vitamin D (VD) has attracted and maintained great interest in human health and biomedical research, particularly those about female reproductive-metabolic problems. Therefore, this study was designed to evaluate the correlation of VD and AMH with PCOS parameters in Egyptian women. Assessments were done on 35 control women and 45 PCOS sufferers. Utilizing the updated Rotterdam criteria, PCOS was identified. After recording anthropometric data, fasting serum levels of VD, follistatin (FST), insulin, FSH, LH, total testosterone (TT), sex hormone binding globulin (SHBG), as well as fasting plasma glucose (FPG), and the free androgen index (FAI) were measured in both groups. Compared to the control group, the PCOS group had a greater prevalence of hypovitaminosis D but serum levels of follistatin, LH, TT, AMH, insulin, and FPG, were considerably higher. Besides, there was a substantial inverse relationship between VD and the levels of follistatin, FPG, LH, TT, and AMH and a positive correlation with FSH in PCOS women's blood. This study revealed that hypovitaminosis D, elevated AMH, and FST may be regarded as alarming risk factors for PCOS in Egyptian women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Inhibiting the CDK2/cyclin A2 enzyme has been validated in multiple clinical manifestations related to multiple types of cancer. Herein, novel series of pyrolo[2,3-c]pyrazole, pyrolo[2,3-c]isoaxazole and pyrolo[2,3-d]pyrimidine, pyrolo[3,2-c]pyridine & indole based analogs were designed, synthesized and biologically evaluated for their in vitro antiproliferative activity where the obtained results revealed that most of the newly synthesized compounds showed significant cytotoxic activity towards MCF-7 (breast cancer cell lines) and HepG-2 (hepatocellular carcinoma) with IC 50 ranging from 3.20 µM to 10.05 µM & from 2.18 µM to 13.49 µM, respectively, compared to that of Sorafenib (IC 50 9.76 & 13.19 µM, respectively). The in vitro inhibitory profile of the most promising compounds (9, 11, 14, 15, 16, 17 and 20) towards CDK2/CyclinA2 was evaluated. Compounds 14 & 15 exhibited potent inhibitory profile against CDK2 with (IC 50 0.11 and 0.262 µM, respectively comparable to Sorafenib IC 50 0.184 µM. Western blotting of 14 & 15 at MCF-7 cell line confirmed the diminishing activity on CDK2. Furthermore, both compounds exserted a significant cell cycle arrest and apoptosis. Moreover, the normal cell line cytotoxicity for both compounds revealed low cytotoxic results in normal cells rather than cancer cells. Molecular docking and dynamic simulation validated the potentiality of the newly synthesized compounds to have high binding affinity within CDK2 binding pocket. 3DQSAR pharmacophore, in-silico ADME/TOPKAT studies and drug-likeness showed proper pharmacokinetic properties and helped in structure requirements prediction. The obtained model and pattern of substitution could be used for further development of CDK2 inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression. Variations in the expression of these short, non-coding RNAs have been associated with various malignancies, including MCC. Although the incidence of MCC is very low, a significant amount of study has focused on the interaction of miRNAs in MCC. As such, the current survey is a speedy intensive route revealing the potential involvement of miRNAs in the pathogenesis of MCC beyond their association with survival in MCC., 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 © 2023 Elsevier GmbH. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare, aggressive form of skin malignancy with a high recurrence commonly within two to three years of initial diagnosis. The incidence of MCC has nearly doubled in the past few decades. Options for diagnosing, assessing, and treating MCC are limited. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play an important role in controlling many different aspects of cell biology. Many miRNAs are aberrantly expressed in distinct types of cancer, with some serving as tumor suppressors and others as oncomiRs. Therefore, the future holds great promise for the utilization of miRNAs in enhancing diagnostic, prognostic, and therapeutic approaches for MCC. Accordingly, the goal of this article is to compile, summarize, and discuss the latest research on miRNAs in MCC, highlighting their potential clinical utility as diagnostic and prognostic biomarkers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Cancer of the salivary glands is one of the five major types of head and neck cancer. Due to radioresistance and a strong propensity for metastasis, the survival rate for nonresectable malignant tumors is dismal. Hence, more research is needed on salivary cancer's pathophysiology, particularly at the molecular level. The microRNAs (miRNAs) are a type of noncoding RNA that controls as many as 30% of all genes that code for proteins at the posttranscriptional level. Signature miRNA expression profiles have been established in several cancer types, suggesting a role for miRNAs in the incidence and progression of human malignancies. Salivary cancer tissues were shown to have significantly aberrant levels of miRNAs compared to normal salivary gland tissues, supporting the hypothesis that miRNAs play a crucial role in the carcinogenesis of salivary gland cancer (SGC). Besides, several SGC research articles reported potential biomarkers and therapeutic targets for the miRNA-based treatment of this malignancy. In this review, we will explore the regulatory impact of miRNAs on the processes underlying the molecular pathology of SGC and provide an up-to-date summary of the literature on miRNAs that impacted this malignancy. We will eventually share information about their possible use as diagnostic, prognostic, and therapeutic biomarkers in SGC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Adrenocortical carcinoma (ACC) is an uncommon aggressive endocrine malignancy that is nonetheless associated with significant mortality and morbidity rates because of endocrine and oncological consequences. Recent genome-wide investigations of ACC have advanced our understanding of the disease, but substantial obstacles remain to overcome regarding diagnosis and prognosis. MicroRNAs (miRNAs, miRs) play a crucial role in the development and metastasis of a wide range of carcinomas by regulating the expression of their target genes through various mechanisms causing translational repression or messenger RNA (mRNA) degradation. Along with miRNAs in the adrenocortical cancerous tissue, circulating miRNAs are considered barely invasive diagnostic or prognostic biomarkers of ACC. miRNAs may serve as treatment targets that expand the rather-limited therapeutic repertoire in the field of ACC. Patients with advanced ACC still have a poor prognosis when using the available treatments, despite a substantial improvement in understanding of the illness over the previous few decades. Accordingly, in this review, we provide a crucial overview of the recent studies in ACC-associated miRNAs regarding their diagnostic, prognostic, and potential therapeutic relevance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Adrenocortical carcinoma (ACC) is a highly malignant infrequent tumor with a dismal prognosis. microRNAs (miRNAs, miRs) are crucial in post-transcriptional gene expression regulation. Due to their ability to regulate multiple gene networks, miRNAs are central to the hallmarks of cancer, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, reprogramming of cellular metabolism, and avoidance of immune destruction. ACC represents a singular form of neoplasia associated with aberrations in the expression of evolutionarily conserved short, non-coding RNAs. Recently, the role of miRNAs in ACC has been examined extensively despite the disease's rarity. Hence, the current review is a fast-intensive track elucidating the potential role of miRNAs in the pathogenesis of ACC besides their association with the survival of ACC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

For the past two decades since their discovery, scientists have linked microRNAs (miRNAs) to posttranscriptional regulation of gene expression in critical cardiac physiological and pathological processes. Multiple non-coding RNA species regulate cardiac muscle phenotypes to stabilize cardiac homeostasis. Different cardiac pathological conditions, including arrhythmia, myocardial infarction, and hypertrophy, are modulated by non-coding RNAs in response to stress or other pathological conditions. Besides, miRNAs are implicated in several modulatory signaling pathways of cardiovascular disorders including mitogen-activated protein kinase, nuclear factor kappa beta, protein kinase B (AKT), NOD-like receptor family pyrin domain-containing 3 (NLRP3), Jun N-terminal kinases (JNKs), Toll-like receptors (TLRs) and apoptotic protease-activating factor 1 (Apaf-1)/caspases. This review highlights the potential role of miRNAs as therapeutic targets and updates our understanding of their roles in the processes underlying pathogenic phenotypes of cardiac muscle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background : Histone deacetylase inhibitors (HDACIs) are a relatively new class of potential drugs for treating cancer. Aim : Discovery of new anticancer agents targeting HDAC. Methods : New uracil and thiouracil derivatives panels were designed and synthesized as HDAC inhibitors. The synthesized compounds were tested against MCF-7, HepG2, and HCT-116. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. The most active member was tested for its potential against cell cycle, apoptosis, caspase-3, and caspase-8. Docking studies were carried out against HDAC1. Results : Compounds 5a , 5b , 5f , 5i , 5k , and 5m exhibited promising cytotoxic activities. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. Regarding the HDAC1 inhibitory activity, compound 5m was the most potent member (IC 50 = 0.05 µg/mL) compared to trichostatin A (IC 50 = 0.0349 µg/mL). For HDAC4, compound 5m showed superior activity (IC 50 = 2.83 µg/mL) than trichostatin A (IC 50 = 3.349 µg/mL) . Compound 5m showed a high potential to arrest the HCT116 cell cycle at the G0-G1 phase. In addition, it showed an almost 17 times apoptotic effect (37.59%) compared to the control cells (2.17%). Furthermore, Compound 5m showed significant increases in the levels of caspase-3 and caspase-8. Finally, the uracil and thiouracil derivatives showed accepted binding mods against HDAC. Conclusions : Compound 5m has potential anticancer activity targeting HDAC with a significant apoptotic effect.

Salivary gland cancer (SGC) is immensely heterogeneous, both in terms of its physical manifestation and its aggressiveness. Developing a novel diagnostic and prognostic detection method based on the noninvasive profiling of microribonucleic acids (miRs) could be a goal for the clinical management of these specific malignancies, sparing the patients' valuable time. miRs are promising candidates as prognostic biomarkers and therapeutic targets or factors that can advance the therapy of SGC due to their ability to posttranscriptionally regulate the expression of various genes involved in cell proliferation, differentiation, cell cycle, apoptosis, invasion, and angiogenesis. Depending on their biological function, many miRs may contribute to the development of SGC. Therefore, this article serves as an accelerated study guide for SGC and the biogenesis of miRs. Here, we shall list the miRs whose function in SGC pathogenesis has recently been determined with an emphasis on their potential applications as therapeutic targets. We will also offer a synopsis of the current state of knowledge about oncogenic and tumor suppressor miRs in relation to SGC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities., 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 © 2023 Elsevier GmbH. All rights reserved.)

Background: Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. Aim: To introduce new active HDAC inhibitors. Methods: Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation. Results: Compounds 7a , 7c , 7d , 7e , 8a and 8f showed the highest antiproliferative effects against MCF7, HepG2 and HCT116 cell lines. Compound 7e exhibited the highest activities against HDAC1 and HDAC4. Compound 7e arrested the cell cycle of HCT116 cells at G0-G1 with significant apoptotic effect. In addition, treatment with compound 7e was associated with a significant increase in the levels of caspase-3 and caspase-8. The docking studies gave good insight about the binding patterns of the synthesized compounds against HDAC1. Conclusion: Compound 7e has a promising anticancer activity targeting HDAC.

Head and neck cancers (HNCs) are a group of heterogeneous tumors formed most frequently from epithelial cells of the larynx, lips, oropharynx, nasopharynx, and mouth. Numerous epigenetic components, including miRNAs, have been demonstrated to have an impact on HNCs characteristics like progression, angiogenesis, initiation, and resistance to therapeutic interventions. The miRNAs may control the production of numerous genes linked to HNCs pathogenesis. The roles that miRNAs play in angiogenesis, invasion, metastasis, cell cycle, proliferation, and apoptosis are responsible for this impact. The miRNAs also have an impact on crucial HNCs-related mechanistic networks like the WNT/β-catenin signaling, PTEN/Akt/mTOR pathway, TGFβ, and KRAS mutations. miRNAs may affect how the HNCs respond to treatments like radiation and chemotherapy in addition to pathophysiology. This review aims to demonstrate the relationship between miRNAs and HNCs with a particular emphasis on how miRNAs impact HNCs signaling networks., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Melanoma is the sixth most frequent malignancy. It represents 1.7% of all cancer cases worldwide. Many risk factors are associated with melanoma including ultraviolet radiation skin phenotype, Pigmented Nevi, Pesticides, and genetic and epigenetic factors. Of the main epigenetic factors affecting melanoma are microribonucleic acids (miRNAs). They are short nucleic acid chains that have the potential to prevent the expression of a number of target genes. They could target a number of genes related to melanoma initiation, stemness, angiogenesis, apoptosis, proliferation, and potential resistance to treatment. Additionally, they can control several melanoma signaling pathways, including P53, WNT/-catenin, JAK/STAT, PI3K/AKT/mTOR axis, TGF- β, and EGFR. MiRNAs also play a role in the resistance of melanoma to essential treatment regimens. The stability and abundance of miRNAs might be important factors enhancing the use of miRNAs as markers of prognosis, diagnosis, stemness, survival, and metastasis in melanoma patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Endometrial cancer (EC) is the 2nd common cancer in females after breast cancer. Besides, it's the most common among gynecological cancers. Several epigenetic factors such as miRNAs have been reported to affect EC aspects including initiation, progression, angiogenesis, and resistance to therapy. miRNAs could regulate the expression of various genes involved in EC pathogenesis. This effect is attributed to miRNAs' effects in proliferation, apoptosis, cell cycle, angiogenesis, invasion, and metastasis. miRNAs also influence crucial EC-related mechanistic pathways such as JAK/STAT axis, EGFR, TGF-β signaling, and P53. Beside pathogenesis, miRNAs also have the potential to affect EC response to treatments including radio and chemotherapy. Thus, this review aims to illustrate the link between miRNAs and EC; focusing on the effects of miRNAs on EC signaling pathways., Competing Interests: Competing interests The authors declare they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Diabetes is the most prevalent metabolic disturbance disease and has been regarded globally as one of the principal causes of mortality. Diabetes is accompanied by several macrovascular complications, including stroke, coronary artery disease (CAD), and cardiomyopathy as a consequence of atherosclerosis. The onset of type 2 diabetes is closely related to insulin resistance (IR). miRNAs have been linked to various metabolic processes, including glucose homeostasis, regulation of lipid metabolism, gluconeogenesis, adipogenesis, glucose transporter type 4 expression, insulin sensitivity, and signaling. Consequently, miRNA dysregulation mediates IR in some target organs, comprising liver, muscle, and adipose tissue. Moreover, miRNAs are crucial in developing diabetes and its associated macrovascular complications through their roles in several signaling pathways implicated in inflammation, apoptosis, cellular survival and migration, the proliferation of vascular smooth muscle cells, neurogenesis, angiogenesis, autophagy, oxidative stress, cardiac remodeling, and fibrosis. Therefore, the purpose of this review is to clarify the role of miRNAs in hepatic, muscle, and adipose tissue IR and explain their roles in the pathogenesis of macrovascular diabetic complications, including stroke, CAD, and cardiomyopathy. Also, explain their roles in gestational diabetes mellitus (GDM). Besides, this review discusses the latest updates on the alteration of miRNA expression in diabetic macrovascular complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bladder cancer (BC) is the 11th most popular cancer in females and 4th in males. A lot of efforts have been exerted to improve BC patients' care. Besides, new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. The miRNAs are either downregulated or upregulated in BC due to epigenetic alterations or biogenesis machinery abnormalities. In BC, dysregulation of miRNAs is associated with cell cycle arrest, apoptosis, proliferation, metastasis, treatment resistance, and other activities. A variety of miRNAs have been related to tumor kind, stage, or patient survival. Besides, although new approaches for using miRNAs in the diagnosis, prognosis, and treatment of BC have been developed, it still needs further investigations. In the next words, we illustrate the recent advances in the role of miRNAs in BC aspects. They include the role of miRNAs in BC pathogenesis and therapy. Besides, the clinical applications of miRNAs in BC diagnosis, prognosis, and treatment are also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations., Competing Interests: Conflict of interest statement The authors declare they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity ( 5 , 8 , 15 , 16 , 17 , and 18 ) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.

Aim: To investigate the change in a serum level of copeptin, a neuroendocrine biomarker, in differentiating grades of COVID-19 severity on admission time and to find its diagnostic potential. Materials & Methods: 160 COVID-19 patients were classified according to disease severity into 80 mild to moderate and 80 severe patients. Serum copeptin level was assessed by ELISA on their admission time. Besides, serum CRP, ferritin and D-dimer were estimated. Results: Severe COVID-19 patients showed higher serum copeptin level in comparison to mild to moderate cases, with diagnostic potential to distinguish disease severity with 93.33% sensitivity and 100% specificity at cutoff value >18.5 Pmol/l. Conclusion: Serum copeptin was remarkably increased with COVID-19 severity with reasonable differentiation potential for recently admitted patients.

The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) patients has been claimed as associated with the risk of COVID-19 infection and its subsequent morbidities and mortalities. These claims were resulting from the possibility of upregulating the expression of angiotensin-converting enzyme 2 (ACE2), facilitation of SARS-CoV-2 entry, and increasing the susceptibility of infection in such treated cardiovascular patients. ACE2 and renin-angiotensin-aldosterone system (RAAS) products have a critical function in controlling the severity of lung injury, fibrosis, and failure following the initiation of the disease. This review is to clarify the mechanisms beyond the possible deleterious effects of angiotensin II (Ang II), and the potential protective role of angiotensin 1-7 (Ang 1-7) against pulmonary fibrosis, with a subsequent discussion of the latest updates on ACEIs/ARBs use and COVID-19 susceptibility in the light of these mechanisms and biochemical explanation., 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., (© 2021 The Author(s).)

Objective: Ficolin-3 is one of the innate immunity molecules that was thought to play a pivotal role in Streptococcus pyogenes autoimmunity and its complications; rheumatic fever (RF) and rheumatic heart disease (RHD). We aimed to disclose if there is an association between ficolin-3 (FCN3) gene polymorphisms (rs4494157 and rs10794501) and RF with or without RHD for the first time in Egyptian adolescents., Results: Serum ficolin-3 level was significantly elevated in patients suffering from RF with and without RHD in comparison with control. Regarding FCN3 gene (rs4494157) polymorphism, a significant correlation was found between the A allele and the susceptibility to RF with or without RHD (OR = 2.93, P = 0.0002 and OR = 2.23, P = 0.008 respectively). Besides, AA homozygous genotype showed a significant association with RHD risk (OR = 3.47, P = 0.026). Patients carrying the A allele (CA + AA) had significantly higher serum ficolin-3 than those carrying the CC genotype (P ˂ 0.0001). While the frequency of (rs10794501) polymorphism revealed no significant differences between the controls and RF patients with or without RHD (OR = 1.43, P = 0.261 and OR = 1.48, P = 0.208 respectively).

Aim: Pancreatic cancer (PC) is one of the most aggressive tumors with dismal survival and a high death rate due to chemotherapeutic failure. P-glycoprotein (P-gp) plays a pivotal role in PC response to gemcitabine and 5-fluorouracil (5-FU). Diltiazem, a calcium channel blocker, is a P-gp inhibitor. In the current study, we investigated the hypothesis that targeting of P-gp by diltiazem can enhance the cytotoxicity of gemcitabine and 5-FU against human pancreatic cancer cells., Main Methods: The cytotoxic effect of diltiazem, gemcitabine, and 5-FU in single and combined forms against PANC-1 and AsPC-1 cells were assayed by MTT. Flow cytometric analysis was used for the determination of cell cycle, apoptosis, and stemness markers in PC cells. Besides, immunoblotting was used for assessment of Bax, caspase 3, cyclin D1, and P-gp expressions., Key Findings: Diltiazem co-treatment, either with gemcitabine or 5-FU, synergistically reduced cell viability, induced apoptosis, and caused cell cycle arrest. In addition, diltiazem co-treatment decreased the expressions of stem cell markers CD24 and CD44, increased the expressions of Bax and cleaved caspase 3, enhanced DNA fragmentation, and attenuated cyclin D1 and P-gp expressions as compared to cells treated with either gemcitabine or 5-FU alone., Significance: Our findings suggest that diltiazem may be potential neoadjuvant therapy to enhance the response of PC to gemcitabine or 5-FU treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)