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Abstract This study is to estimate in‐hospital mortality in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) patients stratified by hemoglobin (Hb) level. Patients were stratified according to hemoglobin level into two groups, that is, Hb 100 g/L. A total of 6931 patients were included. Of these, 6377 (92%) patients had hemoglobin levels >100 g/L. The mean age was 44 ± 17 years, and 66% of the patients were males. The median length of overall hospital stay was 13 days [2; 31]. The remaining 554 (8%) patients had a hemoglobin level 100 g/L (52, 0.82%). Risk factors associated with increased mortality were determined by multivariate analysis. The Kaplan‐Meier survival analysis showed hemoglobin as a predictor of mortality. Cox proportional hazards regression coefficients for hemoglobin for the HB ≤ 100 category of hemoglobin were significant, B = 2.79, SE = 0.17, and HR = 16.34, p

Nowadays, many wrongful acts have been committed in the international community that multiple states play role in its commission. In spite of recognizing Independent Responsibility as the cornerstone basis for allocating international law of responsibility, International Law Commissions (hereinafter ILC) draft Articles on Responsibility of States for Internationally Wrongful Acts (2001) (hereinafter ARSIWA) and its draft Articles on Responsibility of International Organizations (2011) (hereinafter ARIO) have recognized that attribution of acts to one actor does not exclude possible attribution of the same act to another state which is called Derivative Responsibility. Aid or Assistance, Direction and Control, Force and Circumvention of an International Obligation are the only four situations in the scope of derivative responsibility. Despite recognizing these, it is not expressly clarified what kind of relationship exists between them, or how to allocate these two responsibilities as secondary obligation and or how the related contribution is. In the situation of aid or assistance, each one is just responsible of its aid or assistance, so if the wrongdoer commits more internationally wrongful acts, the state in question is just responsible for the aid or assistance and not more; in the situation of direction or control, joint responsibility is applicable; in the situation of force, the forcing party is responsible; so the forced party is not responsible at all; And in the last one, circumvention is not justifiable at all; so the state in question cannot and must not escape from its primary obligation.

ABSTRACT BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders with chronic abdominal pain and altered bowel habit without any organic reason. Sleep disorders may be associated to IBS. OBJECTIVE We aimed to assess sleep disturbances and depression-anxiety-stress in IBS patients. METHODS In this analytical cross sectional study from November 2013 to May 2014, A total of 123 IBS patients were recruited by simple random sampling. IBS was diagnosed using ROME-III criteria. Demographic and basic data were driven from all patients then Pittsburg Sleep Quality Index questionnaire was utilized to estimate sleep quality and DASS (depression anxiety stress scale) questionnaire was filled out for depression, anxiety and stress. RESULTS The mean age of patients was 29±9, where 48 cases (39%) were male. Twelve cases (10%) had a background disease. Types of IBS in patients were included 38% diarrhea, 42% constipation and 20% mixed. From all IBS patients 87 (71%) cases had depression, 97 (79%) patients stress, 94 (76%) patients had anxiety. Seventy-six (62%) cases of IBS patients had poor sleep quality. Simultaneously employing predictors demonstrate that gender, background disease, and type of IBS did not statistically significant. On the other hand, depression (P=0.034, OR=2.35), anxiety (P=0.011, OR=3.022), and stress (P=0.029, OR=2.77) were significantly effect on sleep quality in poor sleepers. CONCLUSION Many of IBS patients is suffering from poor sleep quality. It seems that sleep disorder should be considered and treated in this patients.

چکیدههدف مطالعه حاضر بررسی رابطۀ خودتنظیمی و سازگاری دانش آموزان است. روش تحقیق ازنوع توصیفی است که با روش همبستگی انجام و تحلیل شده است . نمونه شامل 414دانش آموز پایه سوم مدارس راهنمایی شهر سبزوار (شامل 202 پسر و 212 دختر) است که بهروش نمونه گیری خوشه ای چند مرحله ای انتخاب شدند. پرسشنامه خود تنظیمی یادگیری کنلو ریان و پرسشنامه سازگاری دانش آموزان س ی نها و سینگ برای جمع آوری داده ها مورداستفاده قرار گرفت. روایی و پایایی این پرسشنامه ها قبلاً احراز شده بود. برای آزمون رابطۀ بینناسازگاری و خودتنظیمی از ضریب همبستگی پیرسون و رگرسیون چندگانه استفاده شد .،p=0/ یافته ها نشان میدهد که خودتنظیمی با ناسازگاری رابطه منفی معناداری دارد ( 001نتایج رگرسیون چندگانه نیز نشان میدهد خودتنظیمی میتواند ناسازگاری عاطفی .(r= -0/30و اجتماعی را پیش بینی کند. نتایج مقایسه خودتنظیمی و ناسازگاری دانش آموزان دختر و پسرنشان داد که خودتنظیمی و ناسازگاری دانش آموزان دختر و پسر با هم متفاوت است و دخترانبا توجه به یافته های تحقیق میتوان گفت که در .(p

Background: Because of the conflicting results from previous studies regarding the efficacy of ginseng on lipid profile and anti-inflammatory and anti-proliferative activities of its components, we aimed to evaluate the effects of Panax ginseng on lipid profile, pro-oxidant - anti-oxidant status and high-sensitivity C reactive protein (hs-CRP) levels. Methods: Forty Iranian hyperlipidemic patients were randomly assigned to placebo (n = 20) or control (n = 20) groups in this double-blind randomized controlled trial. The ginseng or placebo was taken two capsules twice a day for 8 weeks. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose, serum creatinine and hs-CRP levels and pro-oxidant - anti-oxidant balance (PAB) were estimated before and after intervention. Results: There were no significant differences between the two groups with respect to changes in serum TG, LDL-C, HDL-C, and TC/HDL-C levels. Nor were there significant differences between the two groups with respect to changes in hs-CRP level and PAB from baseline to week 8. Conclusions: Our study demonstrates that ginseng does not have significant effects on lipid profile, Hs-CRP level and PAB. Further clinical studies, with a larger sample size, more prolonged period of therapy are needed to investigate the therapeutic effects of ginseng.

In this study, we present the design, synthesis, and evaluation of six new thiadiazole derivatives designed as VEGFR-2 inhibitors. The most promising compound, 18b, demonstrated promising inhibitory activity against VEGFR-2, with an IC 50 value of 0.165 µg/mL. The in vitro assessments on MCF-7 and HepG2 cell lines revealed the superior anti-proliferative effects of compound 18b, exhibiting IC 50 values of 0.06 and 0.17 µM, respectively. Further investigations into the cell cycle distribution of compound 18b on MCF-7 cells exhibited a cell cycle arrest at the S phase (52.96 %) and significantly reducing the percentage of cells in the G0-G1 and G2/M phases. Additionally, compound 18b demonstrated a remarkable pro-apoptotic effect, with 45.29 % total apoptosis, characterized by both early and late apoptosis, and minimal necrosis. These findings were corroborated by RT-PCR analysis, revealing a significant downregulation of the anti-apoptotic gene Bcl2 and upregulation of the pro-apoptotic gene BAX in compound 18b-treated cells compared to control MCF-7 cells. Moreover, in silico studies involving molecular docking, Density Functional Theory (DFT) calculations, Molecular Dynamics (MD) simulations, MM-GBSA, Principle Component Analysis of Trajectories (PCAT), in addition to Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions underscored the molecular interactions, energetics, and pharmacokinetic properties of compound 18b and the other derivatives further supporting its potential. Our integrated approach, combining in vitro experimens with in silico predictions provides valuable insights into the therapeutic potential of compound 18b as a robust VEGFR-2 inhibitor and lays the groundwork for future optimization., 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 Ltd. All rights reserved.)

Objective: This study aims to investigate the potential of designed 2,3-dihydro-1,3,4-thiadiazole derivatives as anti-proliferative agents targeting VEGFR-2, utilizing a multidimensional approach combining in vitro and in silico analyses., Methods: The synthesized derivatives were evaluated for their inhibitory effects on MCF-7 and HepG2 cancer cell lines. Additionally, VEGFR-2 inhibition was assessed. Further investigations into the cellular mechanisms were conducted to elucidate the effects of 20b ( N -(4-(( E )-1-((( Z )-5-Acetyl-3-( p -tolyl)-1,3,4-thiadiazol-2(3 H )-ylidene)hydrazono) ethyl) phenyl) benzamide) on cell cycle arrest and apoptosis induction. Furthermore, computational investigations, including molecular docking, MD simulations, DFT calculations, MM-GBSA, PCAT, and ADMET predictions were conducted., Results: Compound 20b emerged as a standout candidate with significantly lower IC 50 values of 0.05 μM and 0.14 μM for MCF-7 and HepG2 cell lines, respectively. It exhibited notable VEGFR-2 inhibition (0.024 μM), surpassing the efficacy of sorafenib (0.041 μM). Compound 20b demonstrated cancer-specific targeting potential with a high selectivity index in normal WI-38 cells (IC 50 0.19 μM). Mechanistic studies revealed its ability to arrest the cell cycle of MCF-7 cells and induce apoptosis (total apoptosis 34.47%, early apoptosis 18.48%, and late apoptosis 15.99%), supported by upregulated caspase-8 (3.42-fold) and caspase-9 (5.44-fold) expression. Additionally, 20b arrested the cell cycle of MCF-7 cells at the %G0-G1 phase. Computational investigations provided insights into its molecular interactions with VEGFR-2, contributing to the rational design and understanding of its pharmacological profile., Conclusions: Compound 20b presents as a promising anti-proliferative agent targeting VEGFR-2. Also, this comprehensive investigation underscores the potential of 2,3-dihydro-1,3,4-thiadiazole derivatives as promising candidates for further development in anti-cancer research., Competing Interests: The authors verify that they have no conflicts of interest associated with this publication involving any party or among the co-authors., (This journal is © The Royal Society of Chemistry.)

Background: VEGFR-2 has emerged as a prominent positive regulator of cancer progression., Aim: Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2., Methods: Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. In silico investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed., Results: Compound 15 showed the strongest VEGFR-2 inhibitory activity with an IC 50 value of 0.066 μM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC 50 values ranging from 0.04 to 4.71 μM, relative to sorafenib (IC 50  = 2.24 ± 0.06 and 3.17 ± 0.01 μM against HepG2 and MCF-7, respectively). Also, compound 15 showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound 15 showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound 15 had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound 15 in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound 15 to interact with VEGFR-2., Conclusion: Compound 15 has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vascular endothelial cell proliferation and angiogenesis are all crucially impacted by Endothelial Growth Factor Receptor-2 (VEGFR-2). Its expression is significantly boosted throughout pathologic angiogenesis causing the development of tumors. Sothat, inhibition of VEGFR-2 has crucial role in cancer treatment. In this study, novel semisynthetic theobromine derivatives were rationally designed as VEGFR-2 inhibitors and subjected to in vitro testing for their ability to block VEGFR-2 activation. Furthermore, the antiproliferative effects of these derivatives were evaluated. Compound 7 g exhibited the most potent anti-VEGFR-2 activity, with an IC 50 value of 0.072 µM, and demonstrated excellent dose-dependent inhibitory activity against both MCF-7 and HepG2 cancer cells with IC 50 values of 19.35 and 27.89 µM, respectively. Notably, compound 7 g exhibited high selectivity indices of 2.6 and 1.8 against MCF-7 and HepG2 cells, respectively. Compound 7 g induced G2/M phase cell cycle arrest, promoted apoptosis, and boosted immunomodulation by downregulating TNF- α expression and upregulating IL-2 levels in MCF-7 cells. The molecular docking analysis revealed that compound 7 g could bind effectively to the active site of VEGFR-2, and molecular dynamic simulations confirmed the stability of the VEGFR-2/compound 7 g complex. Furthermore, ADME and toxicity profiling indicated the potential suitability of these compounds as drug candidates. In summary, compound 7 g hold promise as a VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.

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.)

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.)

In this study, a series of seven novel 2,4-dioxothiazolidine derivatives with potential anticancer and VEGFR-2 inhibiting abilities were designed and synthesized as VEGFR-2 inhibitors. The synthesized compounds were tested in vitro for their potential to inhibit VEGFR-2 and the growth of HepG2 and MCF-7 cancer cell lines. Among the compounds tested, compound 22 (IC 50  = 0.079 μM) demonstrated the highest anti -VEGFR-2 efficacy. Furthermore, it demonstrated significant anti-proliferative activities against HepG2 (IC 50  = 2.04 ± 0.06 μM) and MCF-7 (IC 50  = 1.21 ± 0.04 M). Additionally, compound 22 also increased the total apoptotic rate of the MCF-7 cancer cell lines with cell cycle arrest at S phase. As well, computational methods were applied to study the VEGFR-2- 22 complex at the molecular level. Molecular docking and molecular dynamics (MD) simulations were used to investigate the complex's structural and kinetic characteristics. The DFT calculations further revealed the structural and electronic properties of compound 22 . Finally, computational ADMET and toxicity tests were performed indicating the likeness of the proposed compounds to be drugs. The results suggest that compound 22 displays promise as an effective anticancer treatment and can serve as a model for future structural modifications and biological investigations in this field., 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.)

This work presents the synthesis and in vitro , and in silico analyses of new thiadiazole derivatives that are designed to mimic the pharmacophoric characteristics of vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. A comprehensive evaluation of the inhibitory properties of the synthesized thiadiazole derivatives against the cancer cell lines MCF-7 and HepG2 identified several auspicious candidates. Among them, compound 14 showed remarkably low IC 50 values of 0.04 μM and 0.18 μM against MCF-7 and HepG2, respectively. VEGFR-2 inhibitory evaluation of compound 14 revealed a promising IC 50 value in the nanomolar range (103 nM). Further examination of the cell cycle revealed that compound 14 has the ability to stop the progression of the cell cycle in MCF-7 cells via G0-G1 phase arrest. Interestingly, compound 14 also demonstrated a noteworthy pro-apoptotic effect in MCF-7 cells, with notable increases in early apoptosis (16.53%) and late apoptosis (29.57%), along with a slight increase in the population of necrotic cells (5.95%). Furthermore, compound 14 showed a significant drop in MCF-7 cells' ability to migrate and heal wounds. Additionally, compound 14 promoted apoptosis by boosting BAX (6-fold) while lowering Bcl-2 (6.2-fold). The binding affinities of the synthesized candidates to their target (VEGFR-2) were confirmed by computational investigations, including molecular docking, principal component analysis of trajectories (PCAT), and molecular dynamics (MD) simulations. Additionally, compound 14's stability and reactivity were investigated using density functional theory (DFT). These thorough results highlight compound 14's potential as a lead contender for additional research in the creation of anticancer drugs that target VEGFR-2. This work establishes a foundation for promising thiadiazole derivatives for future therapeutic developments in anticancer- and angiogenesis-related scientific fields., Competing Interests: None., (This journal is © The Royal Society of Chemistry.)

The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with the aim of reducing its proliferation and inducing apoptosis. This study aimed at the CADD of a new apoptotic EGFR inhibitor. The natural alkaloid, theobromine, was used as a starting point to obtain a new semisynthetic (di-ortho-chloro acetamide) derivative ( T-1-DOCA ). Firstly, T-1-DOCA 's total electron density, energy gap, reactivity indices, and electrostatic surface potential were determined by DFT calculations, Then, molecular docking studies were carried out to predict the potential of T-1-DOCA against wild and mutant EGFR proteins. T-1-DOCA 's correct binding was further confirmed by molecular dynamics (MD) over 100 ns, MM-GPSA, and PLIP experiments. In vitro, T-1-DOCA showed noticeable efficacy compared to erlotinib by suppressing EGFR WT and EGFR T790M with IC 50 values of 56.94 and 269.01 nM, respectively. T-1-DOCA inhibited also the proliferation of H1975 and HCT-116 malignant cell lines, exhibiting IC 50 values of 14.12 and 23.39 µM, with selectivity indices of 6.8 and 4.1, respectively, indicating its anticancer potential and general safety. The apoptotic effects of T-1-DOCA were indicated by flow cytometric analysis and were further confirmed through its potential to increase the levels of BAX, Casp3, and Casp9, and decrease Bcl-2 levels. In conclusion, T-1-DOCA , a new apoptotic EGFR inhibitor, was designed and evaluated both computationally and experimentally. The results suggest that T-1-DOCA is a promising candidate for further development as an anti-cancer drug., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Novel thiazolidine-2,4-dione derivatives, 11a-g, were designed, and synthesized targeting the VEGFR-2 protein. The in vitro studies indicated the abilities of the synthesized derivatives to inhibit VEGFR-2 and prevent the growth of two different cancer cell types, HepG2 and MCF-7. Compound 11 f exhibited the strongest anti-VEGFR-2 activity (IC 50 = 0.053 µM). As well, compound 11 f showed impressive anti-proliferative activity against the mentioned cancer cell lines with IC 50 values of 0.64 ± 0.01 and 0.53 ± 0.04 µM, respectively. Additionally, compound 11 f arrested the MCF-7 cell cycle at the S phase and increased the overall apoptosis percentage. Furthermore, cell migration assay revealed that compound 11 f has a significant ability to prevent migration and healing potentialities of MCF-7. Moreover, computational studies were used to conduct the molecular investigation of the VEGFR-2-11 f complex. The kinetic and structural features of the complex were examined using molecular dynamics simulations and molecular docking. Besides, Principal component analysis (PCA) was used to explain the dynamics of the VEGFR-2-11 f complex at various spatial scales. The DFT calculations also provided further clarity regarding compound 11 f's structural and electronic features. To evaluate how closely the developed compounds might look like drugs, ADMET and toxicity experiments were computed. To conclude, the presented study demonstrates the potential of compound 11 f as a viable anti-cancer drug, which can serve as a prototype for future structural modifications and further biological investigations., 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 declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2023 Elsevier Ltd. 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.)

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy., 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.)

Pancreatic cancer (PC) has the greatest mortality rate of all the main malignancies. Its advanced stage and poor prognosis place it at the bottom of all cancer sites. Hence, emerging biomarkers can enable precision medicine where PC therapy is tailored to each patient. This highlights the need for new, highly sensitive and specific biomarkers for early PC diagnosis. Prognostic indicators are also required to stratify PC patients. To avoid ineffective treatment, adverse events, and expenses, biomarkers are also required for patient monitoring and identifying responders to treatment. There is substantial evidence that microRNAs (miRs, miRNAs) play a critical role in regulating mRNA and, as a consequence, protein expression in normal and malignant tissues. Deregulated miRNA profiling in PC can help with diagnosis, treatment planning, and prognosis. Furthermore, knowledge of the primary effector genes and downstream pathways in PC can help pinpoint potential miRNAs for use in treatment. Different miRNA expression profiles may serve as diagnostic, prognostic markers, and therapeutic targets across the spectrum of malignant pancreatic illness. Dysregulation of miRNAs has been linked to the malignant pathophysiology of PC through affecting many cellular functions such as increasing invasive and proliferative prospect, supporting angiogenesis, cell cycle aberrance, apoptosis elusion, metastasis promotion, and low sensitivity to particular treatments. Accordingly, in the current review, we summarize the recent advances in the roles of oncogenic and tumor suppressor (TS) miRNAs in PC and discuss their potential as worthy diagnostic and prognostic biomarkers for PC, as well as their significance in PC pathogenesis and anticancer drug 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. The authors have declared that no competing interests exist., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Essential oil nanoemulsions have received much attention due to their biological activities. Thus, a thyme essential oil nanoemulsion (Th-nanoemulsion) was prepared using a safe and eco-friendly method. DLS and TEM were used to characterize the prepared Th-nanoemulsion. Our findings showed that the nanoemulsion was spherical and ranged in size from 20 to 55.2 nm. The micro-broth dilution experiment was used to evaluate the in vitro antibacterial activity of a Th-emulsion and the Th-nanoemulsion. The MIC50 values of the thymol nanoemulsion were 62.5 mg/mL against Escherichia coli and Klebsiella oxytoca , 250 mg/mL against Bacillus cereus , and 125 mg/mL against Staphylococcus aureus. Meanwhile, it emerged that the MIC50 values of thymol against four strains were not detected. Moreover, the Th-nanoemulsion exhibited promising antifungal activity toward A. brasiliensis and A. fumigatus , where inhibition zones and MIC50 were 20.5 ± 1.32 and 26.4 ± 1.34 mm, and 12.5 and 6.25 mg/mL, respectively. On the other hand, the Th-nanoemulsion displayed weak antifungal activity toward C. albicans where the inhibition zone was 12.0 ± 0.90 and MIC was 50 mg/mL. Also, the Th-emulsion exhibited antifungal activity, but lower than that of the Th-nanoemulsion, toward all the tested fungal strains, where MIC was in the range of 12.5-50 mg/mL. The in vitro anticancer effects of Taxol, Th-emulsion, and Th-nanoemulsion were evaluated using the standard MTT method against breast cancer (MCF-7) and hepatocellular carcinoma (HepG2). Additionally, the concentration of VEGFR-2 was measured, and the activities of caspase-8 (casp-8) and caspase-9 (casp-9) were evaluated. The cytotoxic effect was the most potent against the MCF-7 breast cancer cell line after the Th-nanoemulsion treatment (20.1 ± 0.85 µg/mL), and was 125.1 ± 5.29 µg/mL after the Th-emulsion treatment. The lowest half-maximal inhibitory concentration (IC50) value, 20.1 ± 0.85 µg/mL, was achieved when the MCF-7 cell line was treated with the Th-nanoemulsion. In addition, Th-nanoemulsion treatments on MCF-7 cells led to the highest elevations in casp-8 and casp-9 activities (0.66 ± 0.042 ng/mL and 17.8 ± 0.39 pg/mL, respectively) compared to those with Th-emulsion treatments. In comparison to that with the Th-emulsion (0.982 0.017 ng/mL), the VEGFR-2 concentration was lower with the Th-nanoemulsion treatment (0.672 ± 0.019ng/mL). In conclusion, the Th-nanoemulsion was successfully prepared and appeared in nanoform with a spherical shape according to DLS and TEM, and also exhibited antibacterial, antifungal, as well as anticancer activities.

In this study, novel VEGFR-2-targeting thiazolidine-2,4-dione derivatives with potential anticancer properties were designed and synthesized. The ability of the designed derivatives to inhibit VEGFR-2 and stop the growth of three different cancer cell types (HT-29, A-549, and HCT-116) was examined in vitro . The IC 50 value of compound 15, 0.081 μM, demonstrated the best anti-VEGFR-2 potency. Additionally, compound 15 showed remarkable anti-proliferative activities against the tested cancer cell lines, with IC 50 values ranging from 13.56 to 17.8 μM. Additional flow cytometric investigations showed that compound 15 increased apoptosis in HT-29 cancer cells (from 3.1% to 31.4%) arresting their growth in the S phase. Furthermore, compound 15's apoptosis induction in the same cell line was confirmed by increasing the levels of BAX (4.8-fold) and decreasing Bcl-2 (2.8-fold). Also, compound 15 noticeably increased caspase-8 and caspase-9 levels by 1.7 and 3.2-fold, respectively. Computational methods were used to perform molecular analysis of the VEGFR-2-15 complex. Molecular dynamics simulations and molecular docking were utilized to analyze the complex's kinetic and structural characteristics. Protein-ligand interaction profiler analysis (PLIP) determined the 3D interactions and binding conformation of the VEGFR-2-15 complex. DFT analyses also provided insights into the 3D geometry, reactivity, and electronic characteristics of compound 15. Computational ADMET and toxicity experiments were conducted to determine the potential of the synthesized compounds for therapeutic development. The study's findings suggest that compound 15 might be an effective anticancer lead compound and could guide future attempts to develop new drugs., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In this work, new thieno[2,3- d ]pyrimidine-derived compounds possessing potential anticancer activities were designed and synthesized to target VEGFR-2. The thieno[2,3- d ]pyrimidine derivatives were tested in vitro for their abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two types of cancer cells, MCF-7 and HepG2. Compound 18 exhibited the strongest anti-VEGFR-2 potential with an IC 50 value of 0.084 μM. Additionally, it displayed excellent proliferative effects against MCF-7 and HepG2 cancer cell lines, with IC 50 values of 10.17 μM and 24.47 μM, respectively. Further studies revealed that compound 18 induced cell cycle arrest in G2/M phase and promoted apoptosis in MCF-7 cancer cells. Apoptosis was stimulated by compound 18 by increasing BAX (3.6-fold) and decreasing Bcl-2 (3.1-fold). Additionally, compound 18 significantly raised the levels of caspase-8 (2.6-fold) and caspase-9 (5.4-fold). Computational techniques were also used to investigate the VEGFR-2-18 complex at a molecular level. Molecular docking and molecular dynamics simulations were performed to assess the structural and energetic features of the complex. The protein-ligand interaction profiler analysis identified the 3D interactions and binding conformation of the VEGFR-2-18 complex. Essential dynamics (ED) study utilizing principal component analysis (PCA) described the protein dynamics of the VEGFR-2-18 complex at various spatial scales. Bi-dimensional projection analysis confirmed the proper binding of the VEGFR-2-18 complex. In addition, the DFT studies provided insights into the structural and electronic properties of compound 18. Finally, computational ADMET and toxicity studies were conducted to evaluate the potential of the thieno[2,3- d ]pyrimidine derivatives for drug development. The results of the study suggested that compound 18 could be a promising anticancer agent that may provide effective treatment options for cancer patients. Furthermore, the computational techniques used in this research provided valuable insights into the molecular interactions of the VEGFR-2-18 complex, which may guide future drug design efforts. Overall, this study highlights the potential of thieno[2,3- d ]pyrimidine derivatives as a new class of anticancer agents and provides a foundation for further research in this area., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC 50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC 50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

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.)

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic 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 © 2023 Elsevier GmbH. All rights reserved.)

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/β-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM 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., (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.)

A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed and synthesized as possible inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly synthesized compounds were evaluated in vitro for their cytotoxic activities against two human cancer cell lines namely colon cancer (HCT-116) and breast cancer (MCF-7) using sorafenib as a standard anticancer drug. Compounds 9d, 11e, 12b, and 12d showed higher cytotoxic activities than sorafenib with IC 50 values ranging from 1.14 to 10.33 μM. In particular, compound 11e exhibited excellent activities against HCT-116 and MCF-7 with IC 50 values of 1.14 and 1.54 μM, respectively. Moreover, compound 11e exhibited about 47.32-fold cytotoxic activity against normal human fibroblast (WI-38) cells, lower than the cytotoxicity against the cancer cells. Compounds 11e and 12b were the most potent VEGFR-2 inhibitors with IC 50 values of 0.61 and 0.53 μM, respectively, compared to sorafenib. Bedsides, compound 11e arrested the HCT-116 cell growth at S and sub-G1 phases, induced a significant increase in the apoptotic cells, and caused remarkable decrease in the levels of TNF-α, IL-6, and caspase-3. Finally, the binding patterns of the target derivatives were investigated through the docking study against the proposed molecular target (VEGFR-2, PDB ID 1YWN). The results of molecular docking studies showed similar binding modes to sorafenib against VEGFR-2. In addition, molecular dynamic simulations revealed the stability of compound 11e in the active site for 100 ns., Competing Interests: This work was funded by the authors and there is no any conflict of interest., (This journal is © The Royal Society of Chemistry.)

Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly ( p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized tissues were biocompatible with persistent growth of the adipose stem cells over 30 days. The staining confirmed cell adherence either to the peripheries of the materials or within their matrices. Moreover, the in vivo investigation confirmed the biocompatibility and degradability of the decellularized scaffolds. Conclusively, Trypsin + TX + SDS is a successful new protocol for tissue decellularization. Moreover, decellularized pericardia and tunica vaginalis are promising scaffolds for the engineering of different tissues with higher potential for the use of DPP in cardiovascular applications and DBP and DPTV in the reconstruction of higher-stress-bearing abdominal walls.

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.)

Retinoblastoma (RB) is a rare tumor in children, but it is the most common primitive intraocular malignancy in childhood age, especially those below three years old. The RB gene (RB1) undergoes mutations in individuals with RB. Although mortality rates remain high in developing countries, the survival rate for this type of cancer is greater than 95-98% in industrialized countries. However, it is lethal if left untreated, so early diagnosis is essential. As a non-coding RNA, miRNA significantly impacts RB development and treatment resistance because it can control various cellular functions. In this review, we illustrate the recent advances in the role of miRNAs in RB. That includes the clinical importance of miRNAs in RB diagnosis, prognosis, and treatment. Moreover, the regulatory mechanisms of miRNAs in RB and therapeutic interventions are 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.)

Background: VEGFR-2 is one of the most effective targets in cancer treatment. Aim: The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. Methods: In vitro and in silico evaluation of the synthesized compounds. Results: Compound 5b demonstrated excellent antiproliferative and VEGFR-2 inhibitory effects with significant apoptotic activity. It modulated the immune response by increasing IL-2 and reducing TNF-α levels. Docking and molecular dynamics simulations revealed the compound's binding affinity with VEGFR-2. Lastly, computational absorption, distribution, metabolism, excretion and toxicity studies indicated the high potential of compound 5b for drug development. Conclusion: Compound 5b could be a promising anticancer agent targeting VEGFR-2.

The link between the gut microbiome and health has recently garnered considerable interest in its employment for medicinal purposes. Since the early microbiota exhibits more flexibility compared to that of adults, there is a considerable possibility that altering it will have significant consequences on human development. Like genetics, the human microbiota can be passed from mother to child. This provides information on early microbiota acquisition, future development, and prospective chances for intervention. The succession and acquisition of early-life microbiota, modifications of the maternal microbiota during pregnancy, delivery, and infancy, and new efforts to understand maternal-infant microbiota transmission are discussed in this article. We also examine the shaping of mother-to-infant microbial transmission, and we then explore possible paths for future research to advance our knowledge in this area., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. 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.)

Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/β-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Laryngeal cancer (LC)is the malignancy of the larynx (voice box). The majority of LC are squamous cell carcinomas. Many risk factors were reported to be associated with LC as tobacco use, obesity, alcohol intake, human papillomavirus (HPV) infection, and asbestos exposure. Besides, epigenetics as non-coding nucleic acids also have a great role in LC. miRNAs are short nucleic acid molecules that can modulate multiple cellular processes by regulating the expression of their genes. Therefore, LC progression, apoptosis evasions, initiation, EMT, and angiogenesis are associated with dysregulated miRNA expressions. miRNAs also could have some vital signaling pathways such as mTOR/P-gp, Wnt/-catenin signaling, JAK/STAT, KRAS, and EGF. Besides, miRNAs also have a role in the modulation of LC response to different therapeutic modalities. In this review, we have provided a comprehensive and updated overview highlighting the microRNAs biogenesis, general biological functions, regulatory mechanisms, and signaling dysfunction in LC carcinogenesis, in addition to their clinical potential for LC diagnosis, prognosis, and chemotherapeutics response implications., 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.)

High mortality and morbidity rates and variable clinical behavior are hallmarks of glioblastoma (GBM), the most common and aggressive primary malignant brain tumor. Patients with GBM often have a dismal outlook, even after undergoing surgery, postoperative radiation, and chemotherapy, which has fueled the search for specific targets to provide new insights into the development of contemporary therapies. The ability of microRNAs (miRNAs/miRs) to posttranscriptionally regulate the expression of various genes and silence many target genes involved in cell proliferation, cell cycle, apoptosis, invasion, angiogenesis, stem cell behavior and chemo- and radiotherapy resistance makes them promising candidates as prognostic biomarkers and therapeutic targets or factors to advance GBM therapeutics. Hence, this review is like a crash course in GBM and how miRNAs related to GBM. Here, we will outline the miRNAs whose role in the development of GBM has been established by recent in vitro or in vivo research. Moreover, we will provide a summary of the state of knowledge regarding oncomiRs and tumor suppressor (TS) miRNAs in relation to GBM with an emphasis on their potential applications as prognostic 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 © 2023 Elsevier GmbH. All rights reserved.)

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.)

Osteosarcoma (OS) is one of the most common bone cancers that constantly affects children, teenagers, and young adults. Numerous epigenetic elements, such as miRNAs, have been shown to influence OS features like progression, initiation, angiogenesis, and treatment resistance. The expression of numerous genes implicated in OS pathogenesis might be regulated by miRNAs. This effect is ascribed to miRNAs' roles in the invasion, angiogenesis, metastasis, proliferation, cell cycle, and apoptosis. Important OS-related mechanistic networks like the WNT/b-catenin signaling, PTEN/AKT/mTOR axis, and KRAS mutations are also affected by miRNAs. In addition to pathophysiology, miRNAs may influence how the OS reacts to therapies like radiotherapy and chemotherapy. With a focus on how miRNAs affect OS signaling pathways, this review seeks to show how miRNAs and OS are related., 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.)

Cholangiocarcinoma (CCA), the second most frequent liver cancer after hepatocellular carcinoma, has been rising worldwide in recent epidemiological research. This neoplasia's pathogenesis is poorly understood. Yet, recent advances have illuminated the molecular processes of cholangiocyte malignancy and growth. Late diagnosis, ineffective therapy, and resistance to standard treatments contribute to this malignancy's poor prognosis. So, to develop efficient preventative and therapy methods, the molecular pathways that cause this cancer must be better understood. MicroRNAs (miRNAs) are non-coding ribonucleic acids (ncRNAs) that influence gene expression. Biliary carcinogenesis involves abnormally expressed miRNAs that act as oncogenes or tumor suppressors (TSs). The miRNAs regulate multiple gene networks and are involved in cancer hallmarks like reprogramming of cellular metabolism, sustained proliferative signaling, evasion of growth suppressors, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, and avoidance of immune destruction. In addition, numerous ongoing clinical trials are demonstrating the efficacy of therapeutic strategies based on miRNAs as powerful anticancer agents. Here, we will update the research on CCA-related miRNAs and explain their regulation involved in the molecular pathophysiology of this malignancy. Eventually, we will disclose their potential as clinical biomarkers and therapeutic tools in CCA., 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.)

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.)

Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. It has many types, the Papillary thyroid cancer (PTC)(most common and follicular thyroid carcinoma (FTC). Several risk factors have been associated with TC radiation exposure, autoimmunity, and genetics. Microribonucleic acids (miRNAs) are the most important genetic determinants of TC. They are small chains of nucleic acids that are able to inhibit the expression of several target genes. They could target several genes involved in TC proliferation, angiogenesis, apoptosis, development, and even resistance to therapy. Besides, they could influence the stemness of TC. Moreover, they could regulate several signaling pathways such as WNT/β-catenin, PI3K/AKT/mTOR axis, JAK/STAT, TGF- β, EGFR, and P53. Besides signaling pathways, miRNAs are also involved in the resistance of TC to major treatments such as surgery, thyroid hormone-inhibiting therapy, radioactive iodine, and adjuvant radiation. The stability and sensitivity of several miRNAs might be exploited as an approach for the usage of miRNAs as diagnostic and/or prognostic tools in TC., 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.)

Chronic lymphocytic leukemia (CLL) accounts for the vast majority of cases of leukemia. Patients of advanced age are more likely to develop the condition, which has a highly varied clinical course. Consideration of illness features and preceding treatment sequence, as well as patient preferences and comorbidities, is necessary for selecting the appropriate treatment for the appropriate patient. Therefore, there is an urgent need for novel biomarkers with high sensitivity and specificity to detect CLL early, monitor CLL patients, select the treatment responders, and reduce ineffective treatment, unwanted side effects, and unnecessary expenses. In both homeostasis and illness, microRNAs (miRNAs/miRs) play a vital role as master regulators of gene expression and, by extension, protein expression. MiRNAs typically reduce the stability of mRNAs, including those encoding genes involved in tumorigenesis processes as cell cycle regulation, inflammation, stress response, angiogenesis, differentiation, apoptosis, and invasion. Due to their unique properties, miRNAs are rapidly being exploited as accurate biomarkers for illness detection, and medicines based on miRNA targets are finding widespread application in clinical practice. Accordingly, the current review serves as a quick primer on CLL and the biogenesis of miRNAs. In addition to providing a brief overview of the miRNAs whose function in the progression of CLL has been established by recent in vitro or in vivo research through articulating the influence of these miRNAs on a wide variety of cellular functions, including increased proliferative potential; support for angiogenesis; cell cycle aberration; evasion of apoptosis; promotion of metastasis; and reduced sensitivity to specific treatments., 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.)

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.)

In recent decades, obesity has extensively emerged to the level of pandemics. It's significantly associated with serious co-morbidities that could decrease life quality and even life expectancy. Obesity has several determinants, such as age, sex, endocrine, and genetic factors. The miRNAs have emerged as genetic factors affecting obesity. The miRNAs are small noncoding nucleic acids that can modify gene expression and hence, control biological processes. The miRNAs can greatly affect many biological processes in obesity, such as adipogenesis, lipid metabolism, and homeostasis. As a result, the entry of miRNAs in obesity therapeutic approaches has been strongly advised as miRNAs mimics, inhibitors, and stimulators. Hence, this review aims to point out a summarized and updated overview of miRNAs and their roles in obesity and its included processes, such as adipogenesis and lipid metabolism. Besides, we also review recent applications of miRNAs as a treatment approach for obesity., 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.)

Rheumatoid arthritis (RA) is a severe autoimmune inflammation that mostly affects the joints. It's a multifactorial disease. Its clinical picture depends on genetic and epigenetic factors such as miRNAs. The miRNAs are small noncoding molecules that are able to negatively or positively modulate their target gene expression. In RA, miRNAs are linked to its pathogenesis. They disrupt immunity balance by controlling granulocytes, triggering the release of several proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, finally leading to synovium hyperplasia and inflammation. Besides, they also may trigger activation of some pathways as nuclear factor kappa-β disrupts the balance between osteoclast and osteoblast activity, leading to increased bone destruction. Moreover, miRNAs are also applied with efficiency in RA diagnosis and prognosis. Besides the significant association between miRNAs and RA response to treatment, they are also applied as a choice for treatment based on their effects on the immune system and inflammatory cytokines. Hence, the review aims to present an updated overview of miRNAs, their biogenesis, implications in RA pathogenesis, and finally, the role of miRNAs in RA treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. 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.)

Breast cancer (BC) is the most common cancer in women and poses a serious threat to their health. Despite familiarity with factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected previous aspects affecting BC progression and treatment in the last decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting the translation of the target mRNA. miRNAs play a crucial role in BC pathogenesis by promoting cancer stem cell (CSCs) proliferation, postponing apoptosis, continuing the cell cycle, and endorsing invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important BC-related molecular pathways such as the PI3K/AKT/mTOR signaling pathway, the Wnt/β-catenin system, JAK/STAT signaling pathway, and the MAPK signaling pathway. Moreover, miRNAs affect the treatment response of BC to chemo and radiotherapy. Consequently, this review aims to provide an acquainted summary of oncomiRs and tumor suppressor (TS) miRNAs and their potential role in BC pathogenesis and therapy responses by focusing on the molecular pathways that drive them., 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 © 2022 Elsevier B.V. All rights reserved.)

Diabetes mellitus is usually accompanied by nephropathy, retinopathy, and neuropathy as microvascular complications. MicroRNAs (miRNAs) can affect the kidney, retina, and peripheral neurons through their implication in pathways involved in angiogenesis, inflammation, apoptosis, as well as fibrosis within these tissues and hence, play a crucial role in the pathogenesis of microvascular complications. In this review, the updated knowledge of the role of miRNAs in the pathogenesis of diabetic microvascular complications was summarized. PubMed Central was searched extensively to retrieve data from a wide range of reputable biomedical reports/articles published after the year 2000 to systematically collect and present a review of the key molecular pathways mediating the hyperglycemia-induced adverse effects on vascular tissues, particularly in persons with T2DM. In the present review, miR-126, miR-29b, and miR-125a are implicated in diabetes-induced microvascular complications, while miR-146a is found to be connected to all these complications. Also, vascular endothelial growth factors are noted to be the most impacted targets by miRNAs in all diabetic microvascular problems., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)