Modulation of PI3K/AKT signaling and DFT modeling via selected pharmaceutical compounds attenuates carrageenan-induced inflammation and oxidative stress in rats.

The main goal of the current study is to estimate the in vivo anti-inflammatory/antioxidant ability of four selected pharmaceutical compounds: bisoprolol (Biso), piracetam (Pirc), clopidogrel (Clop), and cinnarizine (Cinna). Indomethacin (Indo) was used as a reference drug to perform a realistic comparison between the four compounds and the Indo in vivo through tracking PI3K/AKT signaling and computational chemistry via density functional theory (DFT) modeling to analyze the electrostatic potential across the molecule and provide insight into the regions for receptor binding of the studied compounds. To achieve the safe dose of these compounds, cytotoxicity was performed against isolated adipose tissue-derived mesenchymal stem cells (ADMSCs) using MTT assay.

Active-reset protein sensors enable continuous in vivo monitoring of inflammation.

Continuous measurement of proteins in vivo is important for real-time disease management and prevention. Implantable sensors for monitoring small molecules such as glucose have been available for more than a decade. However, analysis of proteins remains an unmet need because the lower physiological levels require that sensors have high affinities, which are linked to long complexation half-lives ( ~20 hours) and slow equilibration when concentrations decrease.

Identification of VISTA regulators in macrophages mediating cancer cell survival.

Numerous human cancers have exhibited the ability to elude immune checkpoint blockade (ICB) therapies. This type of resistance can be mediated by immune-suppressive macrophages that limit antitumor immunity in the tumor microenvironment (TME). Here, we elucidate a strategy to shift macrophages into a proinflammatory state that down-regulates V domain immunoglobulin suppressor of T cell activation (VISTA) via inhibiting AhR and IRAK1.

Extracellular Release of a Disintegrin and Metalloproteinase Correlates With Periodontal Disease Severity.

Aim: Periodontal disease is driven by oral pathogens, including Porphyromonas gingivalis, and the release of inflammatory cytokines. These cytokines (e.g.

Construction of Topological Bound States in the Continuum Via Subsymmetry.

Topological bound states in the continuum (BICs) are localized topological boundary modes coexisting with a continuous spectrum of extended modes. They have been realized in systems with symmetry-protected topological phases, where their immunity to defects and perturbations depends on the presence of symmetries. Here we propose a method that transforms an in-gap topological boundary state into a BIC by using the concept of subsymmetry.

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation.

While existing synthetic technologies for ex vivo T-cell activation face challenges like suboptimal expansion rates and low effectiveness, artificial antigen-presenting cells (aAPCs) hold great promise for enhanced T-cell based therapies. In particular, gold nanoparticles (AuNPs), known for their biocompatibility, ease of synthesis, and versatile surface chemistry, are strong candidates for use as nanoscale aAPCs. In this study, we developed spiky AuNPs with branched geometries to present activating ligands to primary human T-cells.

Copper/Tin Nanocomposites-Loaded Exosomes Induce Apoptosis and Cell Cycle Arrest at G0/G1 Phase in Skin Cancer Cell Line.

This study aims to explore the efficacy of Copper/Tin (CuS/SnS) nanocomposites loaded into exosomes against skin cancer A431 cell line. CuS/SnS nanocomposites (S1, S2, S3) were synthesized and characterized, then loaded into exosomes (Exo) (S1-Exo, S2-Exo and S3-Exo) and characterized. After that, the loaded samples were investigated in vitro against A431 using cytotoxicity, apoptosis, and cell cycle assays.

Improved long-term survival rate in the responders to bortezomib, cyclophosphamide, dexamethasone induction therapy in a transplant-eligible cohort of predominantly middle-age multiple myeloma patients.

Background: Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking.

Exploration of antimicrobial and anticancer activities of L-amino acid oxidase from Egyptian Naja haje venom.

Hepatocellular carcinoma and bacterial resistance are major health burdens nowadays. Thus, providing new therapies that overcome that resistance is of great interest, particularly those derived from nature rather than chemotherapeutics to avoid cytotoxicity on normal cells. Venomous animals are among the natural sources that assisted in the discovery of novel therapeutic regimens.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses.

An efficient algorithm for resource optimization in IRS-mmWave-NOMA B5G wireless networks.

The effectiveness of implementing intelligent reflecting surface (IRS) for millimeter-wave (mmWave)-non-orthogonal multiple-access (NOMA) systems has allowed for significant sum-rate improvements. The majority of recent research has not discussed how well the IRS-mmWave-NOMA combination performs. Therefore, a new technique for resource optimization in IRS-mmWave-NOMA B5G wireless networks is proposed in this research.

Identification of druggable regulators of cell secretion via a kinome-wide screen and high-throughput immunomagnetic cell sorting.

The identification of genetic regulators of cell secretions is challenging because it requires the sorting of a large number of cells according to their secretion patterns. Here we report the development and applicability of a high-throughput microfluidic method for the analysis of the secretion levels of large populations of immune cells. The method is linked with a kinome-wide loss-of-function CRISPR screen, immunomagnetically sorting the cells according to their secretion levels, and the sequencing of their genomes to identify key genetic modifiers of cell secretion.

Managing Energy Consumption of Devices with Multiconnectivity by Deep Learning and Software-Defined Networking.

Multiconnectivity allows user equipment/devices to connect to multiple radio access technologies simultaneously, including 5G, 4G (LTE), and WiFi. It is a necessity in meeting the increasing demand for mobile network services for the 5G and beyond wireless networks, while ensuring that mobile operators can still reap the benefits of their present investments. Multipath TCP (MPTCP) has been introduced to allow uninterrupted reliable data transmission over multiconnectivity links.

Discrimination between hypervirulent and non-hypervirulent ribotypes of Clostridioides difficile by MALDI-TOF mass spectrometry and machine learning.

Hypervirulent ribotypes (HVRTs) of Clostridioides difficile such as ribotype (RT) 027 are epidemiologically important. This study evaluated whether MALDI-TOF can distinguish between strains of HVRTs and non-HVRTs commonly found in Europe. Obtained spectra of clinical C.

An ellagitannin-loaded CS-PEG decorated PLGA nano-prototype promotes cell cycle arrest in colorectal cancer cells.

Colorectal cancer is associated with significant morbidity and mortality worldwide. Egypt, as a developing country, has a high-rise incidence of cancer. The current study objective was to investigate the antitumor influences of ellagitannin-loaded CS-PEG-decorated PLGA nano-prototypes against human colorectal cancer cell lines (HCT 116 as well as Caco-2) in vitro.

Correlation Between Pre-treatment Collateral Status and Short-Term Functional Outcome in Patients With Mild to Moderate Stroke After Reperfusion Therapy in a Local Primary Stroke Center in the Southwestern Part of Saudi Arabia.

Background Stroke is a substantial cause of disability and mortality worldwide and is characterized by the sudden onset of acute neurological deficit. During acute ischemia, cerebral collateral circulations are crucial in preserving blood supply to the ischemic region. Recombinant tissue plasminogen activator (r-tPA) and endovascular mechanical thrombectomy (MT) are the primary standards of care for acute recanalization therapy.

Anti-cancer activity, and molecular docking of novel hybrid heterocyclic steroids revealed promising anti-hepatocellular carcinoma agent: Implication of cyclin dependent kinase-2 pathway.

To identify new steroidal agents with potential biological activities, we synthesized hybrid steroids containing thiazole, pyrazole, isoxazole, thiophene or phthalazine moiety. Epi-androsterone 1 reacted with phenylthiosemicarbazide to afford the corresponding androstane-4-phenyl-3-thiosemicarbazone derivative 2. The latter product was used in the synthesis of a series of annulated steroid derivatives.

nuPRISM: Microfluidic Genome-Wide Phenotypic Screening Platform for Cellular Nuclei.

Genome-wide loss-of-function screens are critical tools to identify novel genetic regulators of intracellular proteins. However, studying the changes in the organelle-specific expression profile of intracellular proteins can be challenging due to protein localization differences across the whole cell, hindering context-dependent protein expression and activity analyses. Here, we describe nuPRISM, a microfluidics chip specifically designed for large-scale isolated nuclei sorting.

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways.

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo.

Implication of extrinsic and intrinsic apoptotic pathways in the targeted therapy of hepatocellular carcinoma using aptamer-labeled viramidine nanoparticles.

Hepatocellular carcinoma (HCC) is a global health problem with regional differences in epidemiological statistics. Co-assembling the drug nanoparticles and targeting moieties could improve the therapeutic delivery of anti-cancer drugs. In this attempt, we tracked the extrinsic and intrinsic apoptotic pathways in HCC cells using viramidine (VRM)-loaded aptamer (APT) nanoparticles.

Inhibition of induced-hepatic cancer through IQGAP1-shRNA gene therapy and modulation of TRAIL-induced apoptosis pathway.

Background: Liver cancer is the deadliest malignancy among common tumors. It is the top cause of cancer-related deaths in Egypt, and it is characterized by increasing occurrence among the population. The objective of this study was to determine the outcome of pre-treatment of IQGAP1-shRNA on induced mouse hepatocellular carcinoma model and evaluate the potency of this IQGAP1-shRNA plasmid to recover hepatic cancer as a new tool of cancer therapy.

Delayed Presentation of Post-traumatic Multiorgan Left Diaphragmatic Hernia: A Case Report and Literature Review.

Post-traumatic diaphragmatic injuries can present as diaphragmatic hernia with herniation of abdominal viscera into the thoracic cavity. It is challenging for trauma surgeons to identify the delayed presentation of post-traumatic diaphragmatic injuries which require a high index of suspicion in patients who are at risk. We report a rare case of delayed diagnosis and management of post-traumatic diaphragmatic hernia in a polytrauma patient with a concise review of the literature.

Novel Approach Using shRNA of IQGAP1 for Colon Cancer Therapy: HCT116 as a Surrogate Model Colorectal Carcinoma.

Background: Colorectal carcinoma (CRC) represents life-threatening problems worldwide. IQ motif containing GTPase activating protein 1 (IQGAP1) is acting as oncogenesis regulators. RNAi is proposed as promising cancer therapeutics.

Bioactive glass doped with noble metal nanoparticles for bone regeneration: kinetics and proliferative impact on human bone cell line.

This work investigates the bioactivity of novel silver-doped (BG-Ag) and gold-doped (BG-Au) quaternary 46S6 bioactive glasses synthesized a semi-solid-state technique. A pseudo-second-order kinetic model successfully predicted the uptake kinetic profiles of the initial ion-exchange release of Ca in simulated body fluid, the subsequent Si release, and finally, the adsorption of Ca and P onto the bioactive glasses. Doping with silver nanoparticles enhanced the rate of P uptake by up to approximately 90%; whereas doping with gold nanoparticles improved Ca and P uptake rates by up to about 7 and 2 times, respectively; as well as Ca uptake capacity by up to about 19%.

Implementation of a Clostridioides difficile sentinel surveillance system in Germany: First insights for 2019-2021.

Objectives: Clostridioides difficile is a major cause of nosocomial diarrhea. Several "hypervirulent" lineages such as ribotype 027 (RT027) and RT078 are of high epidemiological importance, leading to outbreaks and more severe courses of disease. An active surveillance system targeting molecular epidemiology and corresponding antimicrobial resistance has not been established in Germany.