Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.

Glioblastoma, an aggressive primary brain tumor, poses a significant challenge owing to its dynamic and intricate tumor microenvironment. This review investigates the innovative integration of biosensor-enhanced organ-on-a-chip (OOC) models as a novel strategy for an in-depth exploration of glioblastoma tumor microenvironment dynamics. In recent years, the transformative approach of incorporating biosensors into OOC platforms has enabled real-time monitoring and analysis of cellular behaviors within a controlled microenvironment. Conventional in vitro and in vivo models exhibit inherent limitations in accurately replicating the complex nature of glioblastoma progression. This review addresses the existing research gap by pioneering the integration of biosensor-enhanced OOC models, providing a comprehensive platform for investigating glioblastoma tumor microenvironment dynamics. The applications of this combined approach in studying glioblastoma dynamics are critically scrutinized, emphasizing its potential to bridge the gap between simplistic models and the intricate in vivo conditions. Furthermore, the article discusses the implications of biosensor-enhanced OOC models in elucidating the dynamic features of the tumor microenvironment, encompassing cell migration, proliferation, and interactions. By furnishing real-time insights, these models significantly contribute to unraveling the complex biology of glioblastoma, thereby influencing the development of more accurate diagnostic and therapeutic strategies.

Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages.

Gammaherpesviruses (γHVs) are recognized as important pathogens in humans but their relationship with other animal hosts, especially wildlife species, is less well characterized. Our objectives were to examine natural Eptesicus fuscus gammaherpesvirus (EfHV) infections in their host, the big brown bat (Eptesicus fuscus), and determine whether infection is associated with disease. In tissue samples from 132 individual big brown bats, EfHV DNA was detected by polymerase chain reaction in 41 bats. Tissues from 59 of these cases, including 17 from bats with detectable EfHV genomes, were analyzed. An EfHV isolate was obtained from one of the cases, and electron micrographs and whole genome sequencing were used to confirm that this was a unique isolate of EfHV. Although several bats exhibited various lesions, we did not establish EfHV infection as a cause. Latent infection, defined as RNAScope probe binding to viral latency-associated nuclear antigen in the absence of viral envelope glycoprotein probe binding, was found within cells of the lymphoid tissues. These cells also had colocalization of the B-cell probe targeting CD20 mRNA. Probe binding for both latency-associated nuclear antigen and a viral glycoprotein was observed in individual cells dispersed throughout the alveolar capillaries of the lung, which had characteristics of pulmonary intravascular macrophages. Cells with a similar distribution in bat lungs expressed major histocompatibility class II, a marker for antigen presenting cells, and the existence of pulmonary intravascular macrophages in bats was confirmed with transmission electron microscopy. The importance of this cell type in γHVs infections warrants further investigation.

Investigations on physiochemical and biomedical properties of Aloe vera - Sterculia gum copolymeric dressings impregnated with antibiotic-anesthetic drugs to enhance wound healing.

Recently, various innovative advancements have been made in carbohydrate research to design versatile materials for biomedical applications. The current research focuses on the development of copolymeric hydrogel wound dressings (HWD) using a combination of aloe vera (AV) - sterculia gum (SG) - poly (vinylsulfonic acid) (VSA)-based with the aim to enhancing their efficacy in drug delivery (DD) applications. These hydrogel dressings were encapsulated with levofloxacin and lidocaine to address both microbial infection and pain. Copolymers were characterized by FESEM, SEM, EDS, AFM, 13C NMR, FTIR, XRD, and TGA-DTG analysis. Hydrogel exhibited a fluid absorption capacity of 4.52 ± 0.12 g per gram of polymeric dressing in simulated wound conditions. The hydrogels displayed a sustained release of drugs, demonstrating a non-Fickian diffusion mechanism. Polymer dressings revealed antibacterial, mucoadhesive, antioxidant, biocompatible and non-cytotoxic properties. Additionally, HWD displayed permeability to O2 and water vapour, yet was impermeable to microbial penetration. Overall, the findings of physiological, biochemical and drug delivery properties demonstrated the suitability of materials for wound dressing applications.

Functionalization of sterculia gum for making platform hydrogels via network formation for use in drug delivery.

Recently, various advancements have been made in the development of functional polymeric materials for innovative applications. Herein this work, functionalization of sterculia gum (SG) was carried out via grafting of poly(2-(methacryloyloxy) ethyltrimethylammonium chloride) (METAC)-polyvinyl pyrrolidone (PVP) to develop hydrogel dressings as a platform for use in drug delivery (DD). The innovation of the present work is the exploration of inherent antioxidant and antimicrobial properties of the SG along with antimicrobial characteristic of poly(METAC) and PVP, to design the doxycycline encapsulated hydrogel dressings for better wound healing. FESEM, EDS and AFM analyzed the surface morphology of hydrogels. FTIR, 13C NMR and XRD inferred inclusion of poly(METAC)-PVP into polymers. 13C NMR confirmed the incorporation of poly(METAC) and PVP onto gum by the presence of a peak at 54.74 ppm because of methyl carbon attached to quaternary nitrogen of poly(METAC) and at 45.48 ppm due to the ring carbon of PVP along with FTIR peak at 949 cm-1 because of CN bending of quaternary nitrogen of poy (METAC). Thermal characterization of copolymers has been performed using TGA analysis. One gram of copolymeric hydrogel dressing absorbed 6.51 ± 0.03 g simulated salivary fluid (SSF) and 7.65 ± 0.03 g simulated wound fluid (SWF). Release of doxycycline drug occurred in a sustained manner and followed the Non-Fickian diffusion mechanism from hydrogels. The release profile was most effectively described by Hixon-Crowell kinetic model. Hydrogel demonstrated biocompatibility and expressed thrombogenicity 79.7 ± 4.9 % during its polymer-blood interactions. Copolymer revealed mucoadhesive property, requiring a force of 77.00 ± 0.01 mN to detach from bio-membrane. Additionally, it exhibited antioxidant features, showing 43.81 ± 0.286 % free radical scavenging. Hydrogel dressings were mechanically stable and revealed 0.76 ± 0.09 N mm-2 tensile strength and 9.18 ± 0.01 N burst strength. Polymer films were permeable to oxygen and water vapor and were impermeable to microorganisms. Hydrogel dressings exhibited antimicrobial properties against Pseudomonas aeruginosa and Staphylococcus aureus bacteria. Overall, these properties displayed the suitability of hydrogels for wound dressing (WD) applications which may actively enhance wound healing.

Evaluating physiochemical characteristics of tragacanth gum-gelatin network hydrogels designed through graft copolymerization technique.

The present work deals with the evaluation of the physiochemical and biomedical properties of hydrogels derived from copolymerization of tragacanth gum (TG) and gelatin for use in drug delivery (DD) applications. Copolymers were characterized by field emission-scanning electron micrographs (FE-SEM), electron dispersion X-ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance (NMR), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. FE-SEM revealed heterogeneous morphology and XRD analysis demonstrated an amorphous nature with short range pattern of polymer chains within the copolymers. The release of the drug ofloxacin occurred through a non-Fickian diffusion mechanism and the release profile was best described by the Korsmeyer-Peppas kinetic model. The hydrogels exhibited blood compatibility and demonstrated a thrombogenicity value of 75.63 ±â€¯1.98 % during polymer-blood interactions. Polymers revealed mucoadhesive character during polymer-mucous membrane interactions and required 119 ±â€¯8.54 mN detachment forces to detach from the biological membrane. The copolymers illustrated the antioxidant properties as evidenced by 2, 2'-diphenylpicrylhydrazyl (DPPH) assay which demonstrated a 65.71 ±â€¯3.68 % free radical inhibition. Swelling properties analysis demonstrated that by change in monomer and cross linker content during the reaction increased the crosslinking of the network. These results suggest that the pore size of network hydrogels could be controlled as per the requirement of DD systems. The copolymers were prepared at optimized reaction conditions using 14.54 × 10-1 molL-1 of acrylic acid monomer and 25.0 × 10-3 molL-1 of crosslinker NNMBA. The optimized hydrogels exhibited a crosslink density of 2.227 × 10-4 molcm-3 and a mesh size of 7.966 nm. Additionally, the molecular weight between two neighboring crosslinks in the hydrogels was determined to be 5332.209 gmol-1.The results indicated that the combination of protein-polysaccharide has led to the development of hydrogels suitable for potential applications in sustained drug delivery.

TLR10: An Intriguing Toll-Like Receptor with Many Unanswered Questions.

BACKGROUND: Toll-like receptors (TLRs) are one of the first pattern recognition receptors found in the innate immune system. The TLR family has 12 members (TLR1-TLR9, TLR11-TLR13) in mice and 10 members (TLR1-TLR10) in humans, with TLR10 being the latest identified. SUMMARY: Considerable research has been performed on TLRs; however, TLR10 is known as an orphan receptor for the lack of information on its signalling, role, and ligands. Even though there are recent studies pointing towards the potential TLR10 ligands, their function and signalling pathway are yet to be determined. KEY MESSAGES: This review gives an insight into recent findings on TLR10's pro- and anti-inflammatory properties, with the goal of outlining existing results and indicating future research topics on this receptor.

Evaluation of physiochemical and biomedical properties of psyllium-poly(vinyl phosphonic acid-co-acrylamide)-cl-N,N-methylene bis acrylamide based hydrogels.

Present investigation deals with the synthesis of psyllium based copolymeric hydrogels and evaluation of their physiochemical and biomedical properties. These copolymers have been prepared by grafting of poly(vinyl phosphonic acid) (poly (VPA)) and poly(acrylamide) (poly(AAm)) onto psyllium in the presence of crosslinker N,N-methylene bis acrylamide (NNMBA). These copolymers [psyllium-poly(VPA-co-AAm)-cl-NNMBA] were characterized by field emission-scanning electron micrographs (FE-SEM), electron dispersion X-ray analysis (EDAX), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA)- differential thermal analysis (DTG). FESEM, AFM and XRD demonstrated heterogeneous morphology with a rough surface and an amorphous nature. Diffusion of ornidazole occurred with a non-Fickian diffusion mechanism, and the release profile data was fitted in the Korsemeyer-Peppas kinetic model. Biochemical analysis of hydrogel properties confirmed the blood-compatible nature during blood-polymer interactions and revealed haemolysis value 3.95 ± 0.05 %. The hydrogels exhibited mucoadhesive character during biomembrane-polymer interactions and demonstrated detachment force = 99.0 ± 0.016 mN. During 2,2-diphenyl-1-picrylhydrazyl reagent (DPPH) assay, free radical scavenging was observed 37.83 ± 3.64 % which illustrated antioxidant properties of hydrogels. Physiological and biomedical properties revealed that these hydrogels could be explored for drug delivery uses.

Recent Advancements in Sensing of Silver ions by Different Host Molecules: An Overview (2018-2023).

The chemosensors act as powerful tool in the detection of metal ions due to their simplicity, high sensitivity, low cost, low detection limit, rapid photophysical response, and application to the environmental and medical fields. This review article presents an overview for the chemosensing of Ag+ ions based on Calix, MOF, Nanoparticle, COF, Calix, Electrochemical chemosensor published from 2018 to 2023. Here, we have reviewed the sensing of Ag+ ions and summarised the binding response, mechanism, LOD, colorimetric response, adsorption capacity, technique used. The purpose of this review article to provide a detailed summary of the performance of different host chemosensors that are helpful for providing future direction to researchers on Ag+ ion detection and provides path to design effective chemsosensor (simple to synthesize, cost effective, high sensitivity, with more practical application). While studying the related article literature, we came across some challenges and that has been discussed lastly and provided solutions for them.

Electrochemical synthesis and antimicrobial evaluation of some N-phenyl α-amino acids.

In the present report, the authors describe a synthetic route for the generation of N-phenyl amino acid derivatives using CO2via a C-C coupling reaction in an undivided cell containing a combination of Mg-Pt electrodes. The reactions were completed in a short time without the formation of any other side product. The final products were purified via a simple recrystallization procedure. The structures of the newly prepared compounds were established using advanced spectroscopic techniques including 1H, 13C NMR, IR, and ESI-MS. All the prepared derivatives show good-to-excellent activity when tested against bacterial and fungal strains. Interestingly, it was observed that the presence of polar groups (capable of forming H-bonds) such as -OH (4d) and -NO2 (4e) at the para position of the phenyl ring show activity equivalent to the standard drugs.

Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials.

The identification of prognostic markers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigate the complexity of B and T cell receptor (BCR and TCR) repertoires in the context of two phase III trials, NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women with HER2-positive breast cancer. BCR features, particularly the number of reads and clones, evenness and Gini index, are heterogeneous according to hormone receptor status and PAM50 subtypes. Moreover, BCR measures describing clonal expansion, namely evenness and Gini index, are independent prognostic factors. We present a model developed in NeoALTTO and validated in CALGB 40601 that can predict event-free survival (EFS) by integrating hormone receptor and clinical nodal status, breast pathological complete response (pCR), stromal tumor-infiltrating lymphocyte levels (%) and BCR repertoire evenness. A prognostic score derived from the model and including those variables, HER2-EveNT, allows the identification of patients with 5-year EFS > 90%, and, in those not achieving pCR, of a subgroup of immune-enriched tumors with an excellent outcome despite residual disease.

Electrochemical Biosensors for the Detection of Antibiotics in Milk: Recent Trends and Future Perspectives.

Antibiotics have emerged as ground-breaking medications for the treatment of infectious diseases, but due to the excessive use of antibiotics, some drugs have developed resistance to microorganisms. Because of their structural complexity, most antibiotics are excreted unchanged, polluting the water, soil, and natural resources. Additionally, food items are being polluted through the widespread use of antibiotics in animal feed. The normal concentrations of antibiotics in environmental samples typically vary from ng to g/L. Antibiotic residues in excess of these values can pose major risks the development of illnesses and infections/diseases. According to estimates, 300 million people will die prematurely in the next three decades (by 2050), and the WHO has proclaimed "antibiotic resistance" to be a severe economic and sociological hazard to public health. Several antibiotics have been recognised as possible environmental pollutants (EMA) and their detection in various matrices such as food, milk, and environmental samples is being investigated. Currently, chromatographic techniques coupled with different detectors (e.g., HPLC, LC-MS) are typically used for antibiotic analysis. Other screening methods include optical methods, ELISA, electrophoresis, biosensors, etc. To minimise the problems associated with antibiotics (i.e., the development of AMR) and the currently available analytical methods, electrochemical platforms have been investigated, and can provide a cost-effective, rapid and portable alternative. Despite the significant progress in this field, further developments are necessary to advance electrochemical sensors, e.g., through the use of multi-functional nanomaterials and advanced (bio)materials to ensure efficient detection, sensitivity, portability, and reliability. This review summarises the use of electrochemical biosensors for the detection of antibiotics in milk/milk products and presents a brief introduction to antibiotics and AMR followed by developments in the field of electrochemical biosensors based on (i) immunosensor, (ii) aptamer (iii) MIP, (iv) enzyme, (v) whole-cell and (vi) direct electrochemical approaches. The role of nanomaterials and sensor fabrication is discussed wherever necessary. Finally, the review discusses the challenges encountered and future perspectives. This review can serve as an insightful source of information, enhancing the awareness of the role of electrochemical biosensors in providing information for the preservation of the health of the public, of animals, and of our environment, globally.

Characterization of bioprocessed white and red sorghum flours: Anti-nutritional and bioactive compounds, functional properties, molecular, and morphological features.

In the current investigation, white and red sorghum grains were exposed to bioprocessing techniques, such as soaking, germination, fermentation, and dual processing (both germination and fermentation). Germination and fermentation resulted in improved bioactive profile attributing to better antioxidant activity, whereas a reduction in antinutrient components was observed. On the other hand, soaking had decreased phenolic components and anti-nutritional factors attributing to their leaching in the soaking water. A significant change in the functional properties and color profile was also observed on bioprocessing. It also caused alterations in the morphological structure of the starch-protein matrix and molecular interactions of certain functional groups that reveal the synthesis of certain new bioactive compounds in the flour. The alterations in the bioprocessed flours occurred due to the structural breakdown attributing to the activity of hydrolytic enzymes that were activated during the processing treatments. Bioprocessing was also responsible for the degradation of the starch granules and unfolding of the protein matrix, thus altering the in vitro nutrient digestibility of the flours. Principal component analysis was used to authenticate the differences between different treatments and observations recorded. These bioprocessed flours could be potential ingredients for several valorized cereal products.

CD34 Protein: Its expression and function in inflammation.

CD34 has spear-headed the field of basic research and clinical transplantation since the first reports of its expression on hematopoietic stem cells (HSCs). Expressed in mice, humans, rats and other species, CD34 has been used for more than 40 years as a hematopoietic stem and progenitor cell marker. It was later found that muscle satellite cells and epidermal precursors can also be identified with the aid of CD34. Despite the usefulness of CD34 as a marker of HSCs, its overall purpose in animal physiology has remained unclear. This review recaptures CD34 structure, evolutionary conservation, proposed functions, and role in lung inflammation, to describe current research findings and to provide guidance for future studies on CD34.

Postgraduate training in anaesthesiology - A modular curriculum.

The primary objective of postgraduate medical education is to produce specialists who provide highest quality of health care to suffering patients and return them to the community in the most functional capability. The secondary objective is to advance the cause of science through research and training. A postgraduate, after undergoing the required training in anaesthesiology, should be able to recognise the health needs of the community and apply cognitive and psychomotor skills to provide optimal anaesthetic care. Additionally, the anaesthesiologist should function as a perioperative physician being adept in perioperative care, pain medicine and critical care medicine. The 3-year postgraduate curriculum comprises experience in basic, subspeciality and advanced anaesthesia training. This structured training programme with a curriculum of increasing difficulty and learning incorporates ascending grades of difficulty, posing a challenge to the trainee's intellect and technical skills. Experience in basic anaesthesia training is aimed to lay stress on basic and fundamental aspects of anaesthetic management. Subspeciality anaesthesia training is needed to lay stress on the theory, special considerations and practice of subdisciplines of anaesthesiology. This document proposes a modular-structured, continuous, objectively evaluated, systematic training process that is monitored frequently and periodically, such that the trainee, at the end of training, is capable of appropriate anaesthetic management of disease conditions in a wide variety of situations.

Effect of extrusion processing on techno-functional properties, textural properties, antioxidant activities, in vitro nutrient digestibility and glycemic index of sorghum-chickpea-based extruded snacks.

Physico-chemical, textural, functional, and nutritional properties of the twin screw extruded whole sorghum-chickpea (8:2) snacks was investigated using in vitro procedures. The extruded snacks were analyzed for the effect of variations in extruded conditions on their properties: barrel BT (BT) (130-170°C) and feed moisture (FM) (14%-18%), keeping screw speed constant (400 rpm). The results revealed that specific mechanical energy (SME) decreased (74.4-60.0) in response to rise in both BT and FM, whereas expansion ratio (ER) had shown an alternative relation as it decreased with elevated FM (2.17 at 14%, 130°C to 2.14 at 16%, 130°C) and increased with BT (1.75 at 18%, 130°C to 2.48 at 18%, 170°C). The values of WAI and WSI improved with the surge in BT, which was associated with enhanced disruption of starch granules at higher BT. Raise in FM incremented the total phenolic content (TPC) and hence the antioxidant activity (AA) (FRAP and DPPH) along with the hardness of snacks. As per in vitro starch digestibility is concerned, slowly digestible starch (SDS) content as well as glycemic index (51-53) of the extrudates depressed with increasing BT and FM. Also, lower BT and FM improved the functional properties such as expansion ratio, in-vitro protein digestibility, and overall acceptability of the snacks. A positive correlation was seen among SME and hardness of the snacks, WSI and ER, TPC and AA, SDS and Exp-GI, color and OA, texture and OA.

Adhesion Molecules in Lung Inflammation from Repeated Glyphosate Exposures.

Glyphosate is an active ingredient in herbicides. Exposure to glyphosate-based herbicides has been associated with respiratory dysfunctions in agricultural workers. The ability of inhaled glyphosate to induce lung inflammation is not well understood. Further, the role of adhesion molecules in glyphosate-induced lung inflammation has not been studied. We evaluated lung inflammatory responses from single and repeated glyphosate exposures. Male C57BL/6 mice were intranasally exposed to glyphosate (1 µg/40 µL) for 1 day or once daily for 5 days or 10 days. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected and analyzed. Repeated exposure to glyphosate for 5 days and 10 days resulted in an increase in neutrophils in BAL fluid and higher eosinophil peroxidase levels in lungs, with leukocyte infiltration further confirmed through lung histology. Repetitive exposure to glyphosate increased IL-33 and Th2 cytokines IL-5 and IL-13. A single glyphosate treatment revealed expression for ICAM-1, VCAM-1, and vWF adhesion molecules in the perivascular region of lung sections; with repeated treatment (5 and 10 days), adhesion molecule expression was found in the perivascular, peribronchiolar, and alveolar regions of the lungs. Repetitive exposure to glyphosate induced cellular inflammation in which adhesion molecules may be important to the lung inflammatory process.

Impact of minimally invasive surgery on surgeon health (ISSUE) study: protocol of a single-arm observational study conducted in the live surgery setting.

INTRODUCTION: The rapid evolution of minimally invasive surgery has had a positive impact on patient outcomes; however, it is reported to be associated with work-related musculoskeletal symptoms (WMS) in surgeons. Currently there is no objective measure to monitor the physical and psychological impact of performing a live surgical procedure on the surgeon. METHODS AND ANALYSIS: A single-arm observational study with the aim of developing a validated assessment tool to quantify the impact of surgery (open/laparoscopic/robotic-assisted) on the surgeon. Development and validation cohorts of major surgical cases of varying levels of complexity performed by consultant gynaecological and colorectal surgeons will be recruited. Recruited surgeons wear three Xsens DOT monitors (muscle activity) and an Actiheart monitor (heart rate). Salivary cortisol levels will be taken and questionnaires (WMS and State-Trait Anxiety Inventory) completed by the participants preoperatively and postoperatively. All the measures will be incorporated to produce a single score that will be called the 'S-IMPACT' score. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the East Midlands Leicester Central Research Ethics Committee REC ref 21/EM/0174. Results will be disseminated to the academic community through conference presentations and peer-reviewed journal publications. The S-IMPACT score developed within this study will be taken forward for use in definitive multicentre prospective randomised control trials.