Design, synthesis, and evaluation of novel benzofuran and pyrazole-based derivatives as dual AChE/BuChE inhibitors with antioxidant properties for Alzheimer's disease management.

As a complicated neurodegenerative disorder with several clinical hallmarks, Alzheimer's disease (AD) requires multi-target treatment medicines to address multiple elements of disease progression. In this study, we reported two novel series of compounds: benzofuran-based donepezil analogs (9a-i) and their pyrazole-based counterparts (11a-i) as potential dual inhibitors of AChE and BuChE with additional antioxidant properties, aiming to address multiple pathological aspects of AD simultaneously. The design strategy employed bioisosteric replacement, substituting donepezil's indanone motif with a benzofuran ring in series (9a-i) to maintain crucial hydrogen bonding interactions with the Phe295 residue in the enzyme's active site.

Spiro-fused indoline-quinazoline hybrids as smart bombs against TNF-α-mediated inflammation.

Inflammation is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity.

Molecular docking, DFT and antiproliferative properties of 4-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine as potent anticancer agent with CDK2 and PIM1 inhibition potency.

Due to the limited effeteness and safety concerns associated with current cancer treatments, there is a pressing need to develop novel therapeutic agents. 4-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (3) was synthesized and Initially screened on 59 cancer cell lines showed promising anticancer activity, so, it was chosen for a 5-dose experiment by the NCI/USA. The GI values ranged from 1.

The Efficacy and Safety of Levosimendan in Patients with Advanced Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials.

Background: Intermittent ambulatory levosimendan administration has been shown in several small randomized controlled trials to benefit patients with advanced heart failure, preventing heart failure rehospitalization and mortality. We aim to investigate the totality of high-quality evidence regarding the efficacy and safety of intermittent levosimendan in advanced heart failure patients.

Methods: Up to September 2023, we systematically reviewed the randomized controlled trials indexed in PubMed, Embase Cochrane, SCOPUS, and Web of Science.

Development of new LSM-83177 analogues as anti-tumor agents against colorectal cancer targeting p53-MDM2 interaction.

LSM-83177, a phenoxy acetic acid derivative, is a small molecule reported for its promising anti-tumor properties. Via inhibiting the interaction between MDM2 and p53, LSM-83177 can elevate the active p53 levels within cells, thereby promoting apoptosis and inhibiting tumor growth. Also, LSM-83177 has been shown to inhibit GST activity in colorectal cancer HT29 cells.

Novel imidazo[2,1-b]thiazoles and imidazo[1,2-a]pyridines tethered with indolinone motif as VEGFR-2 inhibitors and apoptotic inducers: Design, synthesis and biological evaluations.

The current study investigates the anticancer and VEGFR-2 inhibitory activities of 16 novel indolinone-grafted imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives (6a-h and 10a-h). The structures of these target compounds were confirmed using elemental and spectral analyses. All compounds were evaluated for their VEGFR-2 inhibitory activity in vitro, with eight compounds demonstrating promising results, exhibiting IC values in the sub-micromolar range (0.

Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI.

Design, Synthesis, and Biological Evaluation of Novel Phenoxy Acetic Acid Derivatives as Selective COX-2 Inhibitors Coupled with Comprehensive Bio-Pharmacological Inquiry, Histopathological Profiling, and Toxicological Scrutiny.

COX-2 plays a key role in converting arachidonic acid into prostaglandins. This makes it a significant target for treating inflammation. Selective COX-2 inhibitors have marked a new phase in inflammatory treatment, providing significant effectiveness while reducing negative side effects.

Design, Synthesis and Biological Assessment of '-(2-Oxoindolin-3-ylidene)-6-methylimidazo[2,1-]thiazole-5-carbohydrazides as Potential Anti-Proliferative Agents toward MCF-7 Breast Cancer.

Breast cancer is a serious threat to the health and lives of women. Two novel series of '-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-]thiazole-5-carbohydrazides and 1-(aryl)-3-(6-methylimidazo[2,1-]thiazol-5-yl)ureas were designed, synthesized and investigated for their anticancer efficacy against the MCF-7 breast cell line. Three compounds of the first series showed potent activity toward MCF-7 with IC in the range 8.

Fragment merging approach for the design of thiazole/thiazolidine clubbed pyrazoline derivatives as anti-inflammatory agents: Synthesis, biopharmacological evaluation and molecular modeling studies.

Fragment merging approach was applied for the design of thiazole/thiazolidinone clubbed pyrazoline derivatives 5a-e, 6a-c, 7 and 10a-d as dual COX-2 and 5-LOX inhibitors. Compounds 5a, 6a, and 6b were the most potent and COX-2 selective inhibitors (IC= 0.03-0.

Potential health risk assessment for heavy metals in Tilapia fish of different spatiotemporal monitoring patterns in Kafr El-Shaikh and El-Faiyum Governorates of Egypt.

Heavy metal (HMs) levels were evaluated in aquacultured tilapia fish collected from two highly producing districts in Egypt (Kafr El-Sheikh and El-Faiyum Governorates) during two seasons (autumn 2021 and spring 2022). As well, health risk assessment of exposure to HMs in tilapia fish was studied. The results revealed that six HMs: As, Cu, Fe, Mn, Cr and Zn were predominant in fish samples of the first season (autumn 2021), while most of HMs were existed in samples of the second season.

Self-perception of Voice Handicap in COVID 19 Patients.

Voice abnormalities were reported in patients during the course of COVID-19 infection. This study aims to evaluate the effect of COVID 19 infection on the self-perception of voice handicap in positive COVID 19 patients in addition to investigating the factors that might correlate with voice handicap if present. Voice handicap index-10 was filled in by 200 patients that were confirmed to be COVID 19 positive based on the RT-qPCR and symptomatology of the disease.

Emerging technology for intraoperative margin assessment and post-operative tissue diagnosis for breast-conserving surgery.

Introduction: Tissue-preserving surgery is utilized progressively in cancer therapy, where a clear surgical margin is critical to avoid cancer recurrence, specifically in breast cancer (BC) surgery. The Intraoperative pathologic approaches that rely on tissue segmenting and staining have been recognized as the ground truth for BC diagnosis. Nevertheless, these methods are constrained by its complication and timewasting for tissue preparation.

Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: a randomized controlled trial.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection.

Environmental protection and energy efficiency improvement by using natural gas fuel in maritime transportation.

Emissions from vessels are a major environmental concern because of their impacts on the deterioration of the environment, especially global warming of the atmosphere. Therefore, the International Maritime Organization (IMO) concerns significant care to environmental protection through the reduction of exhaust emission and improvement of energy efficiency through technical and operational measures. Among the suggested measures from IMO, the alternative fuel such as natural gas has the priority to be used instead of fossil fuels.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibodies in Egyptian Convalescent Plasma Donors.

Using convalescent plasma as immunotherapy is an old method for treatment of infectious diseases. Several countries have recently allowed the use of such therapy for the treatment of COVID-19 patients especially those who are critically ill. A similar program is currently being tested in Egypt.

Numerical analysis of economic and environmental benefits of marine fuel conversion from diesel oil to natural gas for container ships.

Shipping is a significant contributor to global greenhouse gas (GHG) and air pollutant emissions. These emissions mainly come from using diesel fuel for power generation. In this paper, the natural gas is proposed as an alternative marine fuel to be used instead of conventional marine diesel oil.

Assessment of renewable energy supply for green ports with a case study.

Seaports are considered one of the sources involved in the deterioration of the maritime environment due to the excessive amount of exhaust gases emitted from their activities. The majority of seaports depend on the national electric grid as a source of power for the domestic and ships' electric demands. This paper discusses the possibility of shifting ports from relying on the national grid electricity to green power-based ports.

Severe colic mimicking intussusception: a new phenomenon.

Objective: To highlight a new phenomenon that we have encountered in children during the past 5 years. Children in this group have a pathognomonic clinical picture of sudden acute severe abdominal colic during which the child is continuously screaming for 1-2 min. All these patients were initially diagnosed on clinical and ultrasonographic grounds as acute intussusception.

Dosimetric characteristics of an electron multileaf collimator for modulated electron radiation therapy.

Modulated electron radiation therapy (MERT) has been proven as an effective way to deliver conformal dose distributions to shallow tumors while sparing distal critical structures and surrounding normal tissues. It had been shown that a dedicated electron multileaf collimator (eMLC) is necessary to reach the full potential of MERT. In this study, a manually-driven eMLC for MERT was investigated.