Exploring Thieno/Furo[2,3-b]pyridines as new scaffolds for potential FAK inhibition: Design, synthesis, biological evaluation and in silico studies.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a vital role in regulating cancer cell survival, proliferation, migration, and angiogenesis. Aiming to explore new potent inhibitors, a series of thieno/furo[2,3-b]pyridine derivatives was designed and synthesized. The newly synthesized compounds were evaluated for their in vitro anti-proliferative activity against human liver (HUH-7), lung (A549) and breast (MCF-7) cancer cell lines, in addition to their cytotoxic activity against normal lung cell line (WI-38) to predict their safety profile.

Novel thiazolones for the simultaneous modulation of PPARγ, COX-2 and 15-LOX to address metabolic disease-associated portal inflammation.

A hybrid pharmacophore model, based on structural motifs previously identified by our team, was employed to generate ligands that simultaneously target COX-2, 15-LOX, and PPARγ in the context of metabolic dysfunction-associated fatty liver disease (MAFLD). Notable COX-2 inhibitory activities (IC = 0.065-0.

Developing evidence-based guidelines for the safety of symptomatic drugs in multiple sclerosis during pregnancy and breastfeeding: A systematic review and Delphi consensus.

Background: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited.

Microbial profile, antimicrobial resistance, and molecular characterization of diabetic foot infections in a university hospital.

Introduction: Diabetic foot infections (DFIs) are among the most severe complications of diabetes. The aim of this study was to determine the etiological pathogens of DFIs in different Wagner's and IDSA/IWGDF grades, and to assess their antimicrobial susceptibility pattern together with molecular characterization of antibiotic resistance genes.

Methods: A prospective study was conducted on 120 DFI patients at Main Alexandria University Hospital, Egypt.

Effect of remote ischaemic preconditioning on walking in people with multiple sclerosis: double-blind randomised controlled trial.

Background: Remote ischaemic preconditioning (RIPC) is the exposure of body parts to brief periods of circulatory occlusion and reperfusion. Recent studies have also shown that RIPC can improve exercise performance in healthy individuals.

Objective: This study aimed to assess the effect of RIPC on walking in people with multiple sclerosis (MS).

Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones.

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC values of 0.

Rehabilitation Before and After Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for Patients With Multiple Sclerosis (MS): Consensus Guidelines and Recommendations for Best Clinical Practice on Behalf of the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the European Society for Blood and Marrow Transplantation (EBMT).

Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation.

Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies.

TB continues to be a leading health threat despite the availability of powerful anti-TB drugs. We report herein the design and synthesis of various hybrid molecules comprising pyrazine scaffold and various formerly identified anti-mycobacterial moieties. Thirty-one compounds were screened in vitro for their activity against Mycobacterium tuberculosis H37Rv strain using MABA assay.

Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Purpose Of Review: In this review, we summarize the recently published literature that demonstrates the efficacy and safety of autologous haematopoietic stem cell therapy (AHSCT) in multiple sclerosis (MS) and highlight the importance of supportive care required for the safe and well-tolerated delivery of AHSCT.

Recent Findings: MS is an autoimmune inflammatory and degenerative disorder of the central nervous system (CNS). In the majority of patients, the illness runs a relapsing remitting course (RRMS), culminating in a secondary progressive phase with gradual accumulation of fixed disabilities.

Association of diabetic foot ulcers with chronic vascular diabetic complications in patients with type 2 diabetes.

Context: Diabetes mellitus is a common disease which is prevalent globally, presenting with chronic complications and constitutes a major risk to the patient. Diabetic foot ulcers are the single biggest risk factor for non-traumatic lower limb amputations in persons with diabetes. We aimed to screen for the chronic vascular diabetic complications in patients with diabetic foot ulcers (DFUs) and to assess the association of diabetic foot ulcers with these complications in the study group.

Assessment of comorbid mild cognitive impairment and depression in patients with type 2 diabetes mellitus.

Context: Depression, mild cognitive impairment, and dementia are highly prevalent chronic conditions associated with social, medical, and economic burdens. Although there are several epidemiological studies that have reported the prevalence of mild cognitive impairment or depressive syndrome in elderly diabetic population little is known about the comorbidity of these conditions. We aimed to study the prevalence of comorbid mild cognitive impairment (MCI) and depression in patients with Type 2 diabetes mellitus and its relation to glycemic control.

Mechanical Thrombectomy for Acute Ischemic Stroke in Pregnancy.

Intravenous recombinant tissue-plasminogen-activator (rtPA) and mechanical-thrombectomy (MT) are currently the only approved treatments for acute ischemic stroke. Their effectiveness was demonstrated in several clinical trials, and is therefore standard of care. Pregnant women were not included in these studies and consequently the effectiveness and safety in this group are unclear.

Shooting three inflammatory targets with a single bullet: Novel multi-targeting anti-inflammatory glitazones.

In search for effective multi-targeting drug ligands (MTDLs) to address low-grade inflammatory changes of metabolic disorders, we rationally designed some novel glitazones-like compounds. This was achieved by incorporating prominent pharmacophoric motifs from previously reported COX-2, 15-LOX and PPARγ ligands. Challenging our design with pre-synthetic docking experiments on PPARγ showed encouraging results.

Click chemistry inspired copper sulphide nanoparticle-based fluorescence assay of kanamycin using DNA aptamer.

A highly selective and sensitive fluorescence assay for kanamycin has been developed that depends on complementation of two splits of DNA aptamer. One DNA split was labeled with CuS nanoparticle and the other was decorated with biotin, which enabled coupling with streptavidin magnesphere paramagnetic particles (PMPs). Complementation of the two-aptamer splits happened only in the presence of kanamycin and the subsequent sandwich was separated via a magnet.

Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study.

Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays.

Synthesis of Some 1,4,6-Trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles and Their Biological Evaluation as Cytotoxic and Antimicrobial Agents.

A series of novel 1,4,6-trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles supported with some functionalities reported to contribute to significant chemotherapeutic potential were synthesized and evaluated for their antimicrobial and/or cytotoxic activities. Thirteen compounds exhibited cytotoxic potential against a panel of three human tumor cell lines. Compounds 15, 23, and 24 proved to be the most active agents with a broad spectrum of cytotoxic activity.

Isolation, purification and characterisation of transglutaminase from rosemary (Rosmarinus officinalis L.) leaves.

Background: Rosemary (Rosmarinus officinalis L.) is a spice and medicinal herb widely used around the world of the natural antioxidants, and it has been widely accepted as one of the spices with the highest antioxidant activity. Transglutaminase (EC 2.

Increased levels of interleukins 2 and 17 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension.

IIH is a condition of raised intracranial pressure of unknown pathogenesis, which is most commonly seen in young overweight women. This study was designed to confirm and extend previous reports by our and other groups showing increased inflammatory cytokine expression in patients with IIH. We analyzed the concentrations of 14 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17, IL-22, IL-23, IFNγ, TNFα, TGFβ, and osteopontin) in the serum and cerebrospinal fluid (CSF) of 17 patients with IIH and 53 patients with other neurological conditions.

Utilization of salt whey from Egyptian Ras (cephalotyre) cheese in microbial milk clotting enzymes production.

Background: Microbial milk-clotting enzymes are valued as calf rennet substitutes in the cheese industry. The worldwide increase of cheese production coupled with a reduced supply of calf rennet has prompted a search for calf rennet substitutes, including microbial and plant rennets. However, most plant rennets have proved unsuitable because they impart a bitter taste to the cheese.

Concurrence of multiple sclerosis and amyotrophic lateral sclerosis in patients with hexanucleotide repeat expansions of C9ORF72.

Background: Crossover in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) has been described but is poorly understood. A GGGGCC hexanucleotide repeat expansion of C9ORF72 has recently been identified in a significant proportion of patients with ALS.

Methods: In approximately 650 patients diagnosed with ALS from the North of England we identified seven patients who initially presented with MS.

Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.

Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention.