Developing Wolbachia-based disease interventions for an extreme environment.

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae.

Close Kin Dyads Indicate Intergenerational Dispersal and Barriers.

AbstractThe movement of individuals through continuous space is typically constrained by dispersal ability and dispersal barriers. A range of approaches have been developed to investigate these. Kindisperse is a new approach that infers recent intergenerational dispersal (σ) from close kin dyads and appears particularly useful for investigating taxa that are difficult to observe individually.

Patterning-mediated supramolecular assembly of lipids into nanopalms.

At nanoconfined interfaces, a micellar ink of lipids was programmed to transform into various secondary structures such as discs, sheets, or sheet and discs via patterning-mediated self-assembly facilitated by polymer pen lithography. Nanoconfinement with printing force, humidity, temperature, pattern size, and total printing time all governed the intramolecular assembly of lipids and determined their structural shape and size. For example, disc or sheet architectures self-organized to produce cochleates or discotic liquid crystals, respectively.

Spatio-Temporal Modelling Informing Replacement Releases in a Low Rainfall Climate.

Releases of carrying bacteria are known to suppress arbovirus transmission and reduce the incidence of vector-borne diseases. In planning for releases in the arid environment of Jeddah, Saudi Arabia, we collected entomological data with ovitraps across a 7-month period in four locations. Herein, we show that mosquito presence in basements does not differ from that of non-basement areas of buildings.

Custom-made holey graphene scanning probe block co-polymer lithography.

Oxidative chemical etching of metal nanoparticles (NPs) to produce holey graphene (hG) suffers from the presence of aggregated NPs on the graphene surface triggering heterogeneous etching rates and thereby producing irregular sized holes. To encounter such a challenge, we investigated the use of scanning probe block co-polymer lithography (SPBCL) to fabricate precisely positioned silver nanoparticles (AgNPs) on graphene surfaces with exquisite control over the NP size to prevent their aggregation and consequently produce uniformly distributed holes after oxidative chemical etching. SPBCL experiments were carried out printing an ink suspension consisting of poly(ethylene oxide--2-vinylpyridine) and silver nitrate on a graphene surface in a selected pattern under controlled environmental and instrumental parameters followed by thermal annealing in a gaseous environment to fabricate AgNPs.

α-Acid Glycoprotein-Decorated Hyaluronic Acid Nanoparticles for Suppressing Metastasis and Overcoming Drug Resistance Breast Cancer.

Robust inflammation-suppressing nanoparticles based on α-acid glycoprotein (AGP)-conjugated hyaluronic acid nanoparticles (AGP-HA NPs) were designed to regulate breast cancer cells' sensitivity to chemotherapy and to suppress tumor metastasis. The successful conjugation between AGP and HA NPs was confirmed using FTIR, zeta potential, and UV-vis spectroscopy. In vitro studies on MCF-7 cells indicated the remarkable ability of AGP-HA NPs in suppressing migratory tumor ability by 79% after 24 h.

Localizing pharmaceuticals manufacturing and its impact on drug security in Saudi Arabia.

Local production of pharmaceuticals plays a vital role in maintaining resilience of national healthcare systems, especially when it comes to facilitating access to needed medicines and decreasing exposure to imports and international supply chains. Pharma is a research-intensive industry and the systemic lack of governance and support to R&D activities in this sector, among other host of related issues such as unsupportive regulatory regimes and human resources capacity limitations, is one of the major impediments to the diversifying of locally produced pharmaceuticals portfolio. In this review, an overview of the current pharmaceutical production system in Saudi Arabia, its major challenges, and proposed remedies to address them will be highlighted.

Immunotherapy in hematological malignancies: recent advances and open questions.

Over recent years, tremendous advances in immunotherapy approaches have been observed, generating significant clinical progress. Cancer immunotherapy has been shown, in different types of blood cancers, to improve the overall survival of patients. Immunotherapy treatment of hematopoietic malignancies is a newly growing field that has been accelerating over the past years.

Voltage-sensitive sodium channel (Vssc) mutations associated with pyrethroid insecticide resistance in Aedes aegypti (L.) from two districts of Jeddah, Kingdom of Saudi Arabia: baseline information for a Wolbachia release program.

Background: Dengue suppression often relies on control of the mosquito vector, Aedes aegypti, through applications of insecticides of which the pyrethroid group has played a dominant role. Insecticide resistance is prevalent in Ae. aegypti around the world, and the resulting reduction of insecticide efficacy is likely to exacerbate the impact of dengue.

Engineered EV-Mimetic Nanoparticles as Therapeutic Delivery Vehicles for High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women. Several obstacles impede the early diagnosis and effective treatment options for ovarian cancer (OC) patients, which most importantly include the development of platinum-drug-resistant strains. Currently, extensive efforts are being put into the development of strategies capable of effectively circumventing the physical and biological barriers present in the peritoneal cavity of metastatic OC patients, representing a late stage of gastrointestinal and gynecological cancer with an extremely poor prognosis.

Design and Development of D‒α‒Tocopheryl Polyethylene Glycol Succinate‒‒Poly(ε-Caprolactone) (TPGS--PCL) Nanocarriers for Solubilization and Controlled Release of Paclitaxel.

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS--poly(ε-caprolactone) (TPGS--PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS--PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1-5 kDa), as initiators and stannous octoate as a catalyst.

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks.

Development of Epirubicin-Loaded Biocompatible Polymer PLA-PEG-PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment.

Unlabelled: Epirubicin (EPI) is an anti-cancerous chemotherapeutic drug that is an effective epimer of doxorubicin with less cardiotoxicity. Although EPI has fewer side effects than its analog, doxorubicin, this study aims to develop EPI nanoparticles as an improved formula of the conventional treatment of EPI in its free form.

Methods: In this study, EPI-loaded polymeric nanoparticles (EPI-NPs) were prepared by the double emulsion method using a biocompatible poly (lactide) poly (ethylene glycol) poly(lactide) (PLA-PEG-PLA) polymer.

Catalogue of self-targeting nano-medical inventions to accelerate clinical trials.

Repetitive outbreaks and prolonged epidemics represent mortal threats to global health, creating chaos in our globalized world. To date, scientists have been compelled to follow FDA guidelines for conventional clinical trials, which decelerates the release of effective therapies to battle outbreaks and safeguard global health security. Developing multi-purpose platform nanotechnologies to self-target specific organs in response to the disease microenvironment could greatly help to rapidly anticipate and efficiently manage outbreaks.

Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy.

The major impediments to the implementation of cancer immunotherapies are the sustained immune effect and the targeted delivery of these therapeutics, as they have life-threatening adverse effects. In this work, biomimetic metal-organic frameworks [zeolitic imidazolate frameworks (ZIFs)] are used for the controlled delivery of nivolumab (NV), a monoclonal antibody checkpoint inhibitor that was U.S.

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks.

Bismuth oxide nanoparticles induce oxidative stress and apoptosis in human breast cancer cells.

Metal nanomaterials such as bismuth oxide nanoparticles (BiONPs) have been extensively used in cosmetics, dental materials, pulp capping, and biomedical imaging. There is little knowledge about the health risk of BiONPs in humans, which warrants a thorough toxicity investigation of BiONPs at the cellular level. In this experiment, we investigated the cytotoxic effect of BiONPs on human breast cancer (MCF-7) cells over 24 and 48 h.

Shattering barriers toward clinically meaningful MSC therapies.

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies.

Optimized Polyethylene Glycolylated Polymer-Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment.

Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer-lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy.

Methods: ANS loaded PEGylated polymer-lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios.

A proteomic approach towards understanding crypoprotective action of Me2SO on the CHO cell proteome.

Chinese hamster ovary (CHO) cell lines are the most widely used in vitro cells for research and production of recombinant proteins such as rhGH, tPA, and erythropoietin. We aimed to investigate changes in protein profiles after cryopreservation using 2D-DIGE MALDI-TOF MS and network pathway analysis. The proteome changes that occur in CHO cells between freshly prepared cells and cryopreserved cells with and without Me2SO were compared to determine the key proteins and pathways altered during recovery from cryopreservation.

Polymeric Reactor for the Synthesis of Superparamagnetic-Thermal Treatment of Breast Cancer.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub-10 nm SPIONs limit their potential in magnetothermal ablation. We report a facile, efficient, and robust in situ method for the synthesis of SPIONs within a poly(ethylene glycol) (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via the microwave hydrothermal route.

Self-Assembled Metal-Organic Complexes for Thermally Reversible Permeabilization of Cell Membranes.

Natural and synthetic membrane active molecules increase the permeability of cell membranes. This can help cells combat multidrug efflux pumps as well as improve signaling and transfection. In this work, thermoresponsive metal-organic complexes (MOCs) have been constructed to transport cell impermeable cargo across the membrane through a pore-aiding assembly.

Exploring anti-MRSA activity of chitosan-coated liposomal dicloxacillin.

One of the greatest disturbing global health problems is antibiotic-resistant bacterial infections, which have rendered numerous currently used antibiotics ineffective. Thus, the feasibility of chitosan-coated deformable liposomes (C-Lips) containing dicloxacillin (DLX) were evaluated for their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are resistant to beta lactam antibiotics. DLX-loaded liposomes (DLX-Lip) were prepared by a lipid film hydration method and then chitosan (CS) coated (C-DLX-Lip) by the electrostatic deposition method.

Cellular responses of hyaluronic acid-coated chitosan nanoparticles.

In recent years, nanotechnology has been proven to offer promising biomedical applications for diagnostics and drug delivery, stressing the importance of thoroughly investigating the biocompatibility of potentially translatable nanoparticles (NPs). Herein, we report the cellular responses of uncoated chitosan NPs (CS NPs) and hyaluronic acid-coated chitosan NPs (HA-CS NPs) when introduced into Chinese hamster ovary cells (CHO-K1) in a dose-dependent manner (2.5, 0.

Successful Management of Teeth with Different Types of Endodontic-Periodontal Lesions.

Endodontic-periodontal diseases often present great challenges to the clinician in their diagnosis, management, and prognosis. Understanding the disease process through cause-and-effect relationships between the pulp and supporting periodontal tissues with the aid of rational classifications leads to successful treatment outcomes. In this report, we present several treatment modalities in patients with different endodontic-periodontal lesions.