Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents.

An optimization strategy was adopted for designing and synthesizing new series of 2-oxindole conjugates. Selected compounds were evaluated for their antiproliferative effect in vitro against NCI-60 cell lines panel, inhibitory effect on carbonic anhydrase (CA) isoforms (hCAI, II, IX and XII), and protein kinases. Compounds 5 and 7 showed promising inhibitory effects on hCA XII, whereas compound 4d was the most potent inhibitor with low nanomolar CA inhibition against all tested isoforms.

Effectiveness and Role of Using Hyaluronic Acid Injections for Gluteal Augmentation: A Comprehensive Systematic Review of Techniques and Outcomes.

Introduction: There has been a rapid increase in the number of patients undergoing non-surgical gluteal augmentation in recent years, leading to an increase in the number of articles in the literature regarding the use of hyaluronic acid (HA) for gluteal augmentation. No systematic review has been published on the effectiveness of HA for gluteal augmentation. This study aimed to provide a comprehensive review regarding the effectiveness and role of using HA for gluteal augmentation.

Potent Dual Inhibitors of Steroid Sulfatase and 17β-Hydroxysteroid Dehydrogenase Type 1 with a Suitable Pharmacokinetic Profile for Proof-of-Principle Studies in an Endometriosis Mouse Model.

Treating estrogen-dependent diseases like endometriosis with drugs suppressing local estrogen activation may be superior to existing endocrine therapies. Steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) are key enzymes of local estrogen activation. We describe the rational design, synthesis, and biological profilation of furan-based compounds as a novel class of dual STS/17β-HSD1 inhibitors (DSHIs).

Diagnostic significance of hsa_circ_0000146 and hsa_circ_0000072 biomarkers for Diabetic Kidney Disease in patients with type 2 diabetes mellitus.

Background: Diabetic Kidney Disease (DKD) is a significant challenge in healthcare. However, there are currently no reliable biomarkers for renal impairment diagnosis, prognosis, or staging in DKD patients. CircRNAs and microRNAs have emerged as noninvasive and efficient biomarkers.

LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS.

Radical reform of the undergraduate medical education program in a developing country: the Egyptian experience.

Medical educators are in a continuous quest to close the gap between the needs of medical practice and the rising expectations of the communities in their countries. During the past two decades, competency-based medical education has been evolving as an appealing strategy to close this gap. In 2017, the Egyptian medical education authorities mandated all medical schools to change their curricula to comply with revised national academic reference standards, which changed from outcome-based to competency-based.

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p.

Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of , has shown anticancer and hepatoprotective effects. TQ's anticancer effect is mediated through miRNA regulation.

Fracture resistance of prefabricated versus custom-made zirconia crowns after thermo-mechanical aging: an in-vitro study.

Background: Prefabricated zirconia crowns for a young permanent molar is a child-friendly solution for restoring a permanent molar at a young age. This in-vitro study aimed to compare the fracture resistance of prefabricated versus custom-made permanent molar crowns.

Methods: 16 identical resin dies were fabricated to receive permanent molar zirconia crowns, dies were divided into 2 groups, 1) received perfricated crowns, 2) custom-made crowns.

Discovery of novel thioquinazoline--aryl-acetamide/-arylacetohydrazide hybrids as anti-SARS-CoV-2 agents: Synthesis, biological evaluation, and molecular docking studies.

In the current investigation, two novel series of (tetrahydro)thioquinazoline--arylacetamides and (tetrahydro)thioquinazoline--arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline--arylacetamide as well as the tetrahydrothioquinazoline--arylacetohydrazides and showed potent antiviral activity with IC of 21.4, 38.

Novel 2-oxo-2-phenylethoxy and benzyloxy diaryl urea hybrids as VEGFR-2 inhibitors: Design, synthesis, and anticancer evaluation.

Two series of diaryl urea derivatives, 6a-k and 7a-n, were synthesized. All the newly synthesized compounds were tested against the NCI (US) cancer cell lines via SRB assay. The p-chloro-m-trifluoromethyl phenyl derivatives 6e-g and 7e-g showed the most potent cytotoxic activity with a GI value range of 1.

Novel benzenesulfonamide-thiouracil conjugates with a flexible N-ethyl acetamide linker as selective CA IX and CA XII inhibitors.

Novel benzenesulfonamide derivatives linked to diverse functionalized thiouracils through a flexible N-ethyl acetamide linker were designed and synthesized as carbonic anhydrase (CA) inhibitors. The synthesized candidates demonstrated a potent inhibitory activity against four different CA isoforms in the nanomolar range. Compound 10d showed more than twofold higher potency than the reference AAZ against CA II with K of 5.

QSRR modeling of the chromatographic retention behavior of some quinolone and sulfonamide antibacterial agents using firefly algorithm coupled to support vector machine.

Quinolone and sulfonamide are two classes of antibacterial agents with an opulent history of medicinal chemistry features that contribute to their bacterial spectrum, efficacy, pharmacokinetics, and adverse effect profiles. The urgent need for their use, combined with the escalating rate of their resistance, necessitates the development of suitable analytical methods that accelerate and facilitate their analysis. In this study, the advanced firefly algorithm (FFA) coupled with support vector regression (SVR) was used to select the most significant descriptors and to construct two quantitative structure-retention relationship (QSRR) models using a series of 11 selected quinolone and 13 sulfonamide drugs, respectively, to predict their retention behavior in HPLC.

New quinazolinone-based derivatives as DHFR/EGFR-TK inhibitors: Synthesis, molecular modeling simulations, and anticancer activity.

New 2-mercapto-quinazolin-4-one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR-TK) inhibition activities. Compound 24, which is characterized by a 2-benzyl-thio function, showed broad-spectrum anticancer activity with high safety profile and selectivity index. The concentrations of 24 causing 50% growth inhibition (GI ) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC ) were 15.

Regulation of IGF2BP1 by miR-186 and its impact on downstream lncRNAs H19, FOXD2-AS1, and SNHG3 in HCC.

Aim: We have previously characterized oncogenic properties of IGF2BP1 in HCC, and its regulation by short noncoding RNAs (ncRNAs). Recent evidence suggests that IGF2BP1 itself may regulate long ncRNAs (lncRNAs). Therefore, this study aimed at exploring the interplay between IGF2BP1 and various upstream and downstream ncRNAs and its link to HCC pathogenesis.

Regulation of lipid droplet (LD) formation in hepatocytes regulation of SREBP1c by non-coding RNAs.

Introduction: Increased lipogenesis (DNL) is one of the key factors contributing to fat accumulation and non-alcoholic fatty liver disease (NAFLD). Among the critical transcription factors (TFs) regulating DNL is mTOR and its downstream lipogenic TF, SREBP1c. In recent years, it has been established that non-coding RNAs (ncRNAs) play role in both biological processes and disease pathogenesis.

Influence of different personal protective equipment on children's anxiety in dental office: a randomized controlled trial.

Background: A change in how a dentist looks may affect the child's anxiety in the dental office. This study compared the effect of conventional facial PPE versus extra PPE as reusable respirators; on the preoperative child's anxiety in the dental office.

Methods: Fifty two children were randomly allocated into 4 groups, (1) goggles + surgical mask, and (2) face shield + surgical mask versus (3) half-face respirator and (4) full-face respirator.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome.

Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool.

Development and implementation of the AIDA international registry for patients with Schnitzler's syndrome.

Objective: The present paper describes the design, development, and implementation of the AutoInflammatory Disease Alliance (AIDA) International Registry specifically dedicated to patients with Schnitzler's syndrome.

Methods: This is a clinical physician-driven, population- and electronic-based registry implemented for the retrospective and prospective collection of real-life data from patients with Schnitzler's syndrome; the registry is based on the Research Electronic Data Capture (REDCap) tool, which is designed to collect standardized information for clinical research, and has been realized to change over time according to future scientific acquisitions and potentially communicate with other existing or future similar registries.

Results: Since its launch, 113 centers from 23 countries in 4 continents have been involved.

Development and Implementation of the AIDA International Registry for Patients With VEXAS Syndrome.

Objective: The aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.

Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management.

Development and implementation of the AIDA International Registry for patients with Behçet's disease.

Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients with Behçet's disease (BD). The Registry is a clinical physician-driven non-population- and electronic-based instrument implemented for the retrospective and prospective collection of real-life data about demographics, clinical, therapeutic, laboratory, instrumental and socioeconomic information from BD patients; the Registry is based on the Research Electronic Data Capture (REDCap) tool, which is thought to collect standardised information for clinical real-life research, and has been realised to change over time according to future scientific acquisitions and potentially communicate with other existing and future Registries dedicated to BD. Starting from January 31st, 2021, to February 7th, 2022, 110 centres from 23 countries in 4 continents have been involved.

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases.

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs).

Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research.

SARS-CoV-2 and cancer: the intriguing and informative cross-talk.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy.

Platelet and extracellular vesicles in COVID-19 infection and its vaccines.

Platelets are at the crossroads between thrombosis and inflammation. When activated, platelets can shed bioactive extracellular vesicles [pEVs] that share the hemostatic potential of their parent cells and act as bioactive shuttles of their granular contents. In a viral infection, platelets are activated, and pEVs are generated with occasional virion integration.